Is there a haemodynamic advantage associated with cuffed arterial anastomoses?

The development of intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, involving the incorporation of a small section of vein (vein cuff) into the distal anastomosis of PTFE grafts, results in an altered distribution of intimal hyperplasia and improved graft patency rates, especially for below-knee grafts. Numerical simulations have been conducted under physiological conditions to identify the flow behaviour in a typical cuffed bypass model and to determine whether the improved performance of the cuffed system can be accounted for by haemodynamic factors. The flow patterns at the cuffed anastomosis are significantly different to those at the conventional end-to-side anastomosis. In the former case, the flow is characterised by an expansive, low momentum recirculation within the cuff. Separation occurs at the graft heel, and at the cuff toe as the blood enters the recipient artery. Wall shear stresses in the vicinity of the cuff heel are low, but high shear stresses and large spatial gradients in the shearing force act on the artery floor during systole. In contrast, a less disturbed flow prevails and the floor shear stress distribution is less adverse in the conventional model. In conclusion, aspects of the anastomotic haemodynamics are worsened when the cuff is employed. The benefits associated with the cuffed grafts may be related primarily to the presence of venous material at the anastomosis. Therefore, caution is advised with regard to the use of PTFE grafts, pre-shaped to resemble a cuffed geometry.

Numerical investigation of the haemodynamics at a patched arterial bypass anastomosis.

Intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, incorporating a Taylor vein patch into the distal anastomosis of PTFE grafts, results in a decrease in intimal hyperplasia and improved patency rates. Numerical simulations of pulsatile, non-Newtonian blood flow through life-like femorodistal bypass models have been performed to determine whether haemodynamic benefits arise from the modified geometry of the Taylor anastomosis. In a conventional bypass, the distal anastomotic flow exhibited considerable spatial and temporal variations. Steep spatial gradients in the shearing force acted along the floor during systole. The effect of the Taylor geometry was to reduce gradually the momentum of the blood approaching the junction. Thus, flow disturbances were abated, undesirable flow separation at the toe was diminished, and a less adverse floor shear stress distribution prevailed in that case. Intimal thickening should be alleviated at the toe in the Taylor model where separation is reduced, and where the thrombogenic graft surface is replaced with a vein patch. Intimal hyperplasia on the floor may be inhibited in the Taylor model due to more favourable shear stresses. The improved flow through the patched anastomosis should contribute to its enhanced performance.

Computational and experimental simulations of the haemodynamics at cuffed arterial bypass graft anastomoses.

The development of intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, involving the incorporation of a small section of vein (vein cuff) into the distal anastomosis of polytetrafluoroethylene (PTFE) grafts, alters the distribution of intimal hyperplasia and improves graft performance. Numerical and in vitro flow visualization experiments have been conducted to identify the flow behaviour in the cuffed bypass model and to determine whether the improved performance of the cuffed system can be accounted for by haemodynamic factors. The flowfield at the cuffed anastomosis is characterized by an expansive recirculation. Separation occurs at the graft heel, and at the cuff toe as the blood enters the recipient artery. Wall shear stresses in the vicinity of the cuff heel are low, but high shear stresses and large spatial gradients in the shearing force act for a time on the artery floor. In the conventional model, a less disturbed flow prevails while the gradients of shear stress on the floor are smaller. Aspects of the anastomotic haemodynamics are worsened when the cuff is employed. The superior patency rates of cuffed bypasses may not be explained purely on the basis of local haemodynamic factors.

Immune response-mediated protection of adult but not neonatal mice from neuron-restricted measles virus infection and central nervous system disease.

In many cases of neurological disease associated with viral infection, such as measles virus (MV)-induced subacute sclerosing panencephalitis in children, it is unclear whether the virus or the antiviral immune response within the brain is the cause of disease. MV inoculation of transgenic mice expressing the human MV receptor, CD46, exclusively in neurons resulted in neuronal infection and fatal encephalitis within 2 weeks in neonates, while mice older than 3 weeks of age were resistant to both infection and disease. At all ages, T lymphocytes infiltrated the brain in response to inoculation. To determine the role of lymphocytes in disease progression, CD46(+) mice were back-crossed to T- and B-cell-deficient RAG-2 knockout mice. The lymphocyte deficiency did not affect the outcome of disease in neonates, but adult CD46(+) RAG-2(-) mice were much more susceptible to both neuronal infection and central nervous system disease than their immunocompetent littermates. These results indicate that CD46-dependent MV infection of neurons, rather than the antiviral immune response in the brain, produces neurological disease in this model system and that immunocompetent adult mice, but not immunologically compromised or immature mice, are protected from infection.

Induction of single and dual cytotoxic T-lymphocyte responses to viral proteins in mice using recombinant hybrid Ty-virus-like particles.

The induction of cytotoxic T-lymphocyte (CTL) responses to viral proteins is thought to be an essential component of protective immunity against viral infections. Methods for generating such responses in a reproducible manner would be of great value in vaccine development. We demonstrate here that the recombinant antigen-presentation system based on the yeast transposon (Ty) particle-forming p1 protein is a potent means of inducing CTL responses to a variety of viral CTL epitopes, including influenza virus nucleoprotein (two epitopes), Sendai virus and vesicular stomatitis virus nucleoproteins, and the V3 loop of human immunodeficiency virus type-1 (HIV-1) gp120. CTL were primed by hybrid Ty-virus-like particles (VLP) carrying the minimal epitope or as much as 19,000 MW of protein. Ty-VLP carrying two different epitopes (dual-epitope Ty-VLP) were capable of priming CTL responses in two different strains of mice or against two epitopes in the same individual. Furthermore, co-administration of a mixture of two different Ty-VLP carrying single epitopes could induce responses to both epitopes in the same individual. Ty-VLP appear to represent a reproducible and flexible system for inducing CTL responses in mice, and warrant further evaluation in primates.

Modulation of axon diameter and neurofilaments by hypomyelinating Schwann cells in transgenic mice.

Studies of peripheral nerves in two different lines of hypomyelinating transgenic mice support the hypothesis that myelinating Schwann cells exert a significant influence on key biological properties of axons. The mice contain transgenes combining the peripheral myelin protein zero gene (P0) promoter and either the diphtheria toxin A chain gene product or the SV40 (simian virus 40) large T antigen. The consequences of peripheral nerve hypomyelination on axon diameter, neurofilament (NF) density, and NF phosphorylation were analyzed. The sciatic nerves of the P0 diphtheria toxin A transgenic mice (DT) evidenced the most severe hypomyelination, and this was associated with a dramatic decrease in NF phosphorylation plus a marked increase in NF density. In contrast, the sciatic nerves in the P0 SV40 large T antigen transgenic mice (SV40) were not as severely hypomyelinated and there was a milder decrease in NF phosphorylation plus a more modest increase in NF density. Further, the sciatic nerves in both lines evidenced a decrease in axonal caliber without any change in NF content. Taken together, these studies provide strong evidence indicating that myelinating Schwann cells exert a significant influence on axon caliber by modulating NF phosphorylation and NF packing density in the axons of peripheral nerves. Thus, key biological properties of axons are modulated by signals transmitted from myelinating Schwann cells to axons of peripheral nerves.

How common is latex allergy? A survey of children with myelodysplasia.

To estimate the prevalence of latex allergy among children with myelodysplasia, describe the spectrum of associated clinical symptoms and evaluate potential risk factors for the development of latex sensitization, the authors conducted a survey at a regional spina bifida center. The findings suggest that symptomatic latex allergy is frequent among children with myelodysplasia and that those with a history of allergies and/or multiple surgical procedures are at greatest risk of sensitization. Until a sensitive and specific laboratory test for latex allergy is available, clinical history, especially allergy to balloons, may be an inexpensive and convenient way of identifying patients with myelodysplasia who may be at increased risk of more severe reactions and at whom preventive measures, such as reducing latex exposures and/or administration of prophylactic medications, should be targeted.

Feasibility of postpartum rapid hospital discharge: a study from a community hospital population.

We have examined the safety and efficacy of an early postpartum discharge program in 289 patients who were identified prior to delivery and counseled and educated for discharge 12 to 36 hours after delivery. A total of 55% of the study patients were able to be discharged early. There were 4.3% significant maternal problems and 3% significant neonatal problems identified in the first 72 hours after delivery by a nurse practitioner home visit. Significant maternal problems after 72 hours (10%) and neonatal problems (5%) were also found by follow-up visits. The hospital readmission rate was 1.8%. These incidences are consistent with other studies in the literature and suggest that some type of early follow-up of both the mother and infant should routinely accompany early postpartum discharge programs.

Induction of HIV-specific cytotoxic T lymphocytes in vivo with hybrid HIV-1 V3:Ty-virus-like particles.

In general, it has proven difficult to induce CTL responses using simple proteins or peptides without resorting to specialized adjuvants. In this study we show that particulate polymeric Ag in the form of hybrid Ty virus-like particles carrying the V3 region of HIV-1 gp120/160 envelope protein (V3:Ty-VLP) induce V3-specific CTL in BALB/c mice in the absence of adjuvant or lipid vehicle. In vitro restimulation of splenocytes with V3 peptide was necessary in order to generate effector CTL. Th cell activation was not required for this in vitro restimulation phase. The CTL induced by the V3:Ty-VLP were CD8+ve, H-2d-restricted, and HIV-1 isolate-specific (IIIB or MN). Co-administration of IIIB V3:Ty-VLP and MN V3:Ty-VLP primed both IIIB and MN V3-specific CTL. However, only IIIB V3-specific CTL were primed by hybrid Ty-VLP carrying IIIB, MN, and RF V3 loop sequences on the same particle indicating that there is intra- but not intermolecular competition between CTL epitopes. In direct comparisons, V3:Ty-VLP were substantially more potent than rgp120. Rgp160 and a 40mer IIIB V3 peptide both failed to prime V3-specific CTL. These data suggest that the particulate nature of hybrid Ty-VLP facilitates uptake into APC with subsequent access to the MHC class I processing pathway and that they may be useful vaccine vehicles for inducing cytolytic immunity against HIV-1 and other intracellular pathogens.

Dental treatment needs among hospitalized adult mental patients.

This survey determines the dental care needs of hospitalized adults with psychiatric and mental disorders. Comprehensive clinical and radiographic oral examinations, conducted on 33% of the patients in a large state mental hospital, found that extensive unmet needs existed in this population. The major requirements were for prophylaxis, calculus removal, and periodontal therapy. The patients' needs varied depending on several demographic factors, including length of hospitalization and psychiatric diagnoses.

Rapid increases in respiratory epithelial permeability occur after intratracheal instillation of PMA.

We measured pulmonary epithelial permeability by quantifying the disappearance of two water-soluble compounds, [14C]mannitol and [3H]inulin, after their instillation, with and without phorbol myristate acetate (PMA), into gas-filled perfused (50 ml/min) rabbit lungs in situ. Both tracers disappeared in a monoexponential fashion over 30 min with calculated first-order rate constants (control; n = 11) of 0.0008 +/- 0.0002 and 0.0027 +/- 0.0008 min-1 for inulin and mannitol, respectively. The ratio of the rate constants (3.1 +/- 0.5) was not significantly different from the ratio of diffusivities of mannitol:inulin (3.7). Addition of PMA (250 micrograms) significantly (n = 9, P less than 0.05) increased the rate constants for both inulin and mannitol to 0.0024 +/- 0.0007 and 0.0087 +/- 0.0025 min-1, respectively, while not affecting their ratio (4.3 +/- 0.5). Addition of human leukocytes (4-8 X 10(8)/l) to the perfusate did not exacerbate the effect of 250 micrograms PMA (n = 3). The addition of catalase (n = 7) completely inhibited the effect of 250 micrograms PMA. PMA (250 micrograms) did not significantly affect perfusion pressure but increased wet-to-dry weight ratios. Light microscopic histology showed damage to epithelial and endothelial cells after 250 micrograms PMA which was not seen after coinstillation of catalase. Catalase sensitivity of functional and structural effects of PMA suggests that the effect was secondary to production of hydrogen peroxide. Since this effect was noted in lungs not perfused with neutrophils and addition of leukocytes did not exacerbate the increase in permeability, we hypothesize that an undetermined pulmonary cell type was the source of hydrogen peroxide. Finally, we found no evidence for restrictive pores with radii of 0.4-1.4 nm.

Pulmonary extraction of [3H]bupivacaine: modification by dose, propranolol and interaction with [14C]5-hydroxytryptamine.

The authors studied the single-pass pulmonary extraction of the potent local anesthetic, bupivacaine, in 21 anesthetized rabbits. Pulmonary extraction of [3H]bupivacaine and [14C]5-hydroxytryptamine (5-HT) was quantified from multiple indicator-dilution outflow curves using indocyanine green as the intravascular reference substance. Pulmonary extraction at control (n = 15; mean +/- S.D.) was 81 +/- 6 and 78 +/- 9% for [3H]bupivacaine and [14C]5-HT, respectively. The apparent volume of distribution of bupivacaine was 38 +/- 9 ml/kg compared with 12 +/- 4 ml/kg for indocyanine green. Simultaneous administration of up to 300 micrograms/kg of bupivacaine did not affect the disposition of either radiolabeled amine; however, injection of 1000 micrograms/kg of bupivacaine significantly (P less than .01) depressed pulmonary extraction of both [3H]bupivacaine and [14C]5-HT. In the presence of 1000 micrograms/kg bupivacaine, the apparent volume of distribution of [3H]bupivacaine decreased to 24 +/- 9 ml/kg (P less than .01). Fifteen minutes after administration of propranolol (100-250 micrograms/kg i.v.), [14C]5-HT removal was unchanged, but the pulmonary extraction of [3H]bupivacaine was significantly decreased to 70 +/- 12% (n = 6; P less than .01). These data suggest that bupivacaine is extensively removed as it enters the lung and that the removal process is a combination of passive diffusion and a small component of saturable specific binding. The interaction of bupivacaine with 5-HT may be part of this specific binding (i.e., endothelial cell uptake) or may have been secondary to direct effects of large concentrations of bupivacaine on membrane function.(ABSTRACT TRUNCATED AT 250 WORDS)

Beagle puppy model of perinatal cerebral infarction. Regional cerebral prostaglandin changes during acute hypoxemia.

Perinatal cerebral infarction, or stroke, is a not uncommon finding in newborns who survive after intensive care. Asphyxia, with its component parts hypoxemia and hypotension, represents the most common cause of perinatal cerebral infarction and may result in neuropathological changes in the periventricular white matter. Previous studies have demonstrated regional alterations in cerebral blood flow (CBF) in response to hypoxemic insult. This work examines the effects of hypoxemia on regional cerebral prostaglandin levels in the developing brain, since some observers believe that local CBF is controlled in part by prostaglandins. In this study, newborn beagle pups were anesthetized, subjected to tracheotomy and artificially ventilated to maintain normoxemia and normocarbia. Mean arterial blood pressure (MABP) was continuously monitored by means of an indwelling catheter and transducer, and craniectomies were performed. When the pups were physiologically stabilized, they were randomly assigned to receive acute hypoxemic insult (pO2 14.0 +/- 1.55 mm Hg, mean +/- standard deviation) accomplished by altering the oxygen concentration in the inspired air) or to receive no insult (mean pO2 84.3 +/- 13.0 mm Hg). Fifteen minutes following stable hypoxemic or normoxic conditions, all pups underwent in vivo freezing of the intracranial contents under anesthesia followed by rapid sacrifice. No significant differences were noted between the MABP, pH, or pCO2 values for the control and hypoxemic pups during the experimental period. Regional cerebral prostaglandin data demonstrated a significant increase in prostaglandin (PG)E2 in the gray matter of hypoxemic pups when compared to the normoxic controls (p less than 0.02). No significant differences were noted for 6-keto-PGE1 alpha, the stable metabolite of prostacyclin, or thromboxane (TX)B2, the stable metabolite of TXA2, in the gray matter. In addition, although 6-keto-PGE1 alpha was significantly lower in the periventricular white matter of the hypoxemic pups (p less than 0.05), there were no changes in the white matter in either PGE2 or TXA2. This regional differential synthesis of PGE2 in response to hypoxemic insult may explain the relative failure of CBF to the periventricular white matter and thus the neuropathological alterations attributed to it.