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.     

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.     

Nasal response of rhinitic and non-rhinitic subjects to histamine and methacholine: a comparative study.

The nasal responses to provocation with histamine and methacholine were compared in 20 subjects with and 20 without rhinitis. Two variables were measured: nasal airways resistance and the development of rhinorrhoea. Histamine had a greater effect than methacholine in increasing nasal airways resistance while the converse was true for rhinorrhoea. Rhinitic subjects had a significantly greater response to histamine induced changes in nasal airways resistance (p less than 0.05), rhinorrhoea (p less than 0.05) and methacholine induced rhinorrhoea (p less than 0.01) than those without rhinitis. No significant differences were found between the two groups in methacholine induced changes in nasal airways resistance. The findings show that, like the lower airways of patients with asthma, the nasal mucosa of rhinitic subjects shows a greater responsiveness to non-specific agonists than that of non-rhinitic subjects.     

Application of adjunct techniques in cytologic material in the diagnosis of rhabdomyosarcoma: case report and review of the literature

A 4(1/2)-yr-old female presented with right-sided pleural effusion and a retroperitoneal mass. Cytologic analysis of the pleural fluid yielded malignant small round blue cells, which were noncohesive, 3-4 times the size of lymphocytes. The malignant cells had hyperchromatic, pleomorphic nuclei with moderate amounts of vacuolated cytoplasm. A few fiber-shaped cells were also seen. Immunostains for desmin, muscle-specific actin were positive; ultrastructural findings of thick and thin actin-myosin filaments confirmed the diagnosis of embryonal rhabdomyosarcoma. This case illustrates the importance of performing appropriate immunohistochemical stains and ultrastructural studies on cytological material to arrive at a definitive diagnosis.     

Emotional abuse, self-blame, and self-silencing in women with irritable bowel syndrome

OBJECTIVE: The purpose of this study was to investigate the presence of emotional abuse and two psychosocial constructs (self-blame and self-silencing) in a sample of women diagnosed with irritable bowel syndrome (IBS) relative to a comparison sample of women diagnosed with inflammatory bowel disease (IBD). METHODS: Women diagnosed with IBS (N = 25) were compared with women diagnosed with IBD (N = 25) on measures of history of abuse, self-blame, and self-silencing. RESULTS: It was found that women in the IBS sample scored significantly higher on emotional abuse, self-blame, and self-silencing than did women in the IBD sample. These three variables were also found to be significantly intercorrelated in both the IBS and IBD samples. Finally, emotional abuse was significantly higher in IBS patients than in IBD patients beyond the differences accounted for by physical and/or sexual abuse history. CONCLUSIONS: These findings empirically demonstrate an association between IBS and emotional abuse, as well as a possible connection with psychosocial variables, that may mediate the connection between emotional abuse and functional bowel symptoms. We suggest that these variables be further evaluated in the context of clinically relevant research on IBS.     

Nature's Swiss Army Knife: The Diverse Protective Roles of Anthocyanins in Leaves

Anthocyanins, the pigments responsible forspectacular displays of vermilion in the leaves of deciduoustrees, have long been considered an extravagant waste of aplant's resources. Contemporary research, in contrast, has begunto show that the pigments can significantly influence the way aleaf responds to environmental stress. Anthocyanins have beenimplicated in tolerance to stressors as diverse as drought,UV-B, and heavy metals, as well as resistance toherbivores and pathogens. By absorbing high-energy quanta,anthocyanic cell vacuoles both protect chloroplasts from thephotoinhibitory and photooxidative effects of strong light, andprevent the catabolism of photolabile defence compounds.Anthocyanins also mitigate photooxidative injury in leaves byefficiently scavenging free radicals and reactive oxygen species.Far from being a useless by-product of the flavonoid pathway,these red pigments may in some instances be critical for plant survival.