Vascular Access for Therapeutic Plasma Exchange

Abstract: Adequate venous access is an essential component of therapeutic plasma exchange (TPEX). The simplest kind of venous access is venipuncture of antecubital veins, but this technique may be limited by venous size or scarring following the procedure, requiring the placement of a specialized vascular access device (VAD). VADs provide reliable central venous access and may remain in place for several weeks or months, depending on the VAD and the venous site chosen. Their use, however, is potentially limited by the risk of complications. We discuss indications for insertion, choice of catheter and access site, and complications of VAD placement for TPEX.     

The role of connective tissue in inhibiting epithelial downgrowth on titanium-coated percutaneous implants.

Ideally, the surface of epithelium-penetrating implants should impede apical epithelial migration. Previous studies have shown that micromachined grooved surfaces can produce connective-tissue ingrowth, which inhibits epithelial downgrowth on percutaneous implants [Chehroudi et al., J. Biomed. Mater. Res., 24, 9, (1990)]. However, in those studies, connective tissue and epithelium interacted with the same surface so that the effects of the surfaces on each population could not be determined separately. The objectives of this study were (a) to examine cell behavior on implants in which connective tissue contacted surfaces of various topographies and epithelium encountered only a smooth surface, and (b) to compare one-stage and two-stage surgical techniques. Implants had a base component (BC) which was either smooth or had a surface with 19-micron- or 30-micron-deep grooves or 120-micron-deep tapered pits, and a skin-penetrating component (SPC) which was smooth. In the two-stage technique, the BC was implanted subcutaneously for 8 weeks, which permitted the healing of the peri-implant connective tissue. In the second stage the SPC was connected to the BC. For one-stage implants, BC & SPC were connected and implanted percutaneously. Implants (BC & SPC) were removed 1, 2, or 3 weeks after percutaneous implantation and histological sections were measured for recession, connective tissue and epithelial attachment as well as capsule thickness. Light microscopy indicated that both grooved and tapered pitted surfaces encouraged connective tissue ingrowth. On the grooved surfaces, the orientation of fibroblasts changed from an oblique to a more complex pattern which included cells having round nuclei within the grooves, as well as cells oriented oblique or perpendicular to the grooves. In the tapered pits a hammock-like arrangement of fibroblasts was observed. In some cases, foci of mineralization and formation of bonelike tissue were found on the grooved and pitted surfaces. The apical migration of the epithelium was significantly (p less than 0.05) inhibited by those micromachined surfaces which produced connective tissue ingrowth to the BC. This study found that placing the implants in two stages improved the performance of percutaneous devices, and that a further improvement was achieved if the implant had a surface promoting connective tissue ingrowth.     

Reconstruction of soft tissue injuries of the foot and ankle with microsurgical techniques

Microsurgical reconstruction for injuries of the foot and ankle includes, in addition to repair of small nerves, vessels, and tendons, coverage of soft tissue defects. Local transpositional and island pedicle flaps are ideal when available and adequate. The choice of free vascularized flaps is based on its potential durability, contour, bulk, and appearance. Thin cutaneous flaps, fascial flaps, and muscle flaps covered with split thickness skin grafts are appropriate in specific areas. Neurosensory flaps and methods of reinnervation may have a place in extensively denervated feet. Good postoperative pedorthic care aids in the final outcome.     

Development of a novel class of cyclic hexapeptide oxytocin antagonists based on a natural product.

A new structural class of cyclic hexapeptide oxytocin antagonists derived from Streptomyces silvensis and typified by L-365,209 (cyclo-[L-prolyl1-D-phenylalanyl2-L- isoleucyl3-D-dehydropiperazyl4-L-dehydroperazyl5-D-(N- methyl)phenylalanyl6]) was recently reported. In this paper we further delineate the structure-activity profile for this new class by systematic study of L-365,209 analogs obtained by total synthesis. The optimal combination of cyclic amino acid ring sizes at positions 1, 4, and 5 and the role of the N-alkyl substituent at position 6 was elucidated. The lipophilic amino acids at positions 2 and 3 and the unusual amino acid D-dehydropiperazic acid at position 4 were found to be the most critical residues for obtaining good oxytocin receptor affinity. Analogs containing a basic side chain at the less critical 5- and 6-positions maintained good receptor affinity and also had useful levels of water solubility for intravenous formulation. By combining potency- and solubility-enhancing substitutions, several analogs were identified that have the desired combination of properties in vitro (22, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L-pipeco lyl-D- histidyl]; 25, cyclo-[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L -pipecolyl-D- histidyl]; 26, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-dehydropiperazyl-L-++ pipecolyl-D-histidyl]; 33, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L- piperazinylcarboxy-D-(N-methyl)phenylalanyl]; 34, cyclo-[L-prolyl-D-phenylalanyl-L-isoleucyl-D-dehydropiperazyl-L-or nithyl- D-(N-methyl)phenylalanyl]). In general, this class exhibited good selectivity for binding to the oxytocin receptor versus the arginine vasopressin V1a and V2 receptor subtypes, although increased V2 receptor affinity was observed in one case (32, cyclo[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L- lysyl-D-(N- methyl)phenylalanyl]). Unexpectedly, compound 33 was found to stimulate contractions of the isolated rat uterus via activation of the uterine bradykinin receptor. Compounds 22, 25, 26, 33, and 34 were found to be potent antagonists of oxytocin-stimulated contraction of the rat uterus in vitro and in vivo. Compounds 22 and 25 were additionally characterized as potent antagonists of oxytocin-stimulated uterine contractions in the near-term pregnant rhesus monkey. These studies thus demonstrate the selectivity and efficacy of certain members of this novel class of antagonists and suggest their use as pharmacological tools in further defining the role of oxytocin in both term and preterm labor.     

Accidental Occupational Farm Fatalities in North Carolina: 1984 to 1988

Development of interventions to prevent accidental occupational fatalities requires the prior identification of those at risk and the circumstances surrounding the injuries. A survey of unintentional farm fatalities was conducted using medical examiner reports (RIME) and death certificates (MECD) to identify deaths due to agricultural occupational injuries in North Carolina from 1984 through 1988. Of 393 cases, 123 met the criteria "farmer" listed as occupation on the RIME/MECD and/or "victim" in a rural area performing a farming task when injured. A second aim of this study was to use an existing data base to achieve maximum accuracy in identifying true cases of work-related farm fatalities.
A fatality rate of 41/100,000 agricultural workers was found; the National Institutes of Occupational Safety and Health's National Traumatic Occupational Fatality study criteria would have identified only 57 percent of these. Victims were characterized as middle age (53 years), white (76%), male (100%), full-time farmers (65%). Injury occurred during harvest season on Monday or Tuesday (47%) between 2 and 6 p.m. (54%). Death was pronounced at the scene (74%), with probable cause listed as tractor (62%). Injury location and land elevation were also related, with the mountain region having twice the fatality rate as the coastal plains region.     

Validity in hermeneutic phenomenological inquiry: towards an ethics of evaluation.

This article explores the relationship of ethics to validity in hermeneutic phenomenological inquiry. First, the authors present a brief overview of the various discourses on validity in qualitative research that have been variously applied to hermeneutic phenomenological inquiry. Next, they examine how relational ethics is a presence to bear within this form of inquiry. Finally, they offer a set of ethical reflections to help the researcher engage in a process of ethical questioning during each step of the research process.     

Stereotaxic Interstitial Laser Therapy of Early-Stage Breast Cancer

Abstract: Coagulation leading to fibrosis of mammo-graphically detected breast cancers by interstitial laser therapy was tested as an alternative to surgical removal. Availability of computerized stereotaxic digital imaging allows the precise placement of laser and thermal needles into the target tumor and its controlled ablation by heat. The methodology of interstitial laser therapy (ILT), evolution of the subsequently removed tumors, and their histologic appearance are outlined.
Eight patients with mammographically well-defined tumors were selected. Definitive diagnosis and receptor evaluation were made on core biopsies. Under local anesthesia, stereotaxically guided diode laser energy at 5–10 w was delivered via a 400 xm fiber in a 19-gauge needle placed into the center of the tumor until the peripheral temperature exceeded 60°C. Patients experienced transient pain and pyrexia. Subsequent to ILT, seven invasive carcinomas were excised while one case of multiple papillomas was kept under surveillance. Histologic study revealed central necrosis but some peripheral residual tumor in the first five cases. In the last two, central necrosis surrounded by concentrically arranged, recognizable but severely injured, focally "windswept" and "ghostlike" tumor and granulation tissue were noted. The multiple papillomas showed radiologic shrinkage at 5 months and extensive fibrosis on needle biopsy.
ILT is an attractive new method of treating small, well-defined breast tumors and offers a potentially significant alternative to surgical removal; further exploration is warranted.     

Mood Matters: Negative Mood Induction Activates Dysfunctional Attitudes in Women Vulnerable to Depression

Cognitive theory holds that dysfunctionalattitudes are important risk factors for depression.Critics have questioned this view, noting that, althoughdysfunctional attitudes are elevated in depression, they are not evident in vulnerable individualswho are asymptomatic. To deal with this criticism,Miranda and Persons (1988) have advanced the mood-statedependent hypothesis, which suggests that cognitive vulnerability factors are indeed present invulnerable individuals, but remain dormant untilactivated by negative mood. To test this hypothesis, 33women with and 67 women without histories of depression reported dysfunctional attitudes before andafter a film negative mood induction. As predicted,vulnerable subjects who reported increased negative moodreported increased dysfunctional attitudes.Unexpectedly, nonvulnerable subjects who reported increasednegative mood reported decreased dysfunctionalattitudes. These findings support the mood-statedependent hypothesis, and suggest that a deficit in theability to regulate negative emotions may be animportant feature of vulnerability todepression.