Treatment of severe chronic venous insufficiency using the subfascial endoscopic perforator vein procedure.

BACKGROUND: Before 1985, corrective surgical procedures for patients with chronic venous insufficiency and venous ulcers were performed using long incisions through diseased skin and subcutaneous tissues. The procedure, involving ligation of incompetent perforator veins, known as "the Linton operation," often was complicated by wound infections and poor healing. This changed in 1985 when G. Hauer demonstrated a new surgical technique for direct visual identification of the incompetent perforator veins using an endoscope in the subfascial space. This seminal contribution marked the advent of subfascial endoscopic perforator vein surgery (SEPS). METHODS: From 1996 to 2004, the authors group prospectively collected data on 110 patients with chronic venous insufficiency who underwent a SEPS procedure. Preoperative assessment of the limb's vascular status consisted of color-flow duplex ultrasound imaging and ascending and descending phlebography to locate vein valve incompetence, along with venous mapping. The ages of the patients ranged from 42 to 82 years (mean, 60 years). A total of 128 limbs underwent the SEPS procedure in the cohort of 110 patients. According to CEAP classification for venous limb disease, 60 limbs belonged to group C5 (skin changes, pigmentation, venous eczema, lipodermatosclerosis, healed ulcer) and 68limbs to group C6 (skin changes and active ulceration). RESULTS: The 110 patients underwent 128 SEPS procedures without significant morbidity. Of the 68 limbs in class C6, 54 showed ulcer healing within the follow-up period of 12 weeks. The remaining 14 limbs in class C6 achieved ulcer healing within 24 weeks. In this latter group, 10 patients had venous ulcers larger than 4 cm in diameter. These patients underwent a split-thickness skin graft at the time the SEPS procedure was performed. The grafts remained healed during a 2-year follow-up period. CONCLUSIONS: This study demonstrated the effectiveness of the SEPS procedure when incorporated into the overall treatment strategy for patients with chronic venous insufficiency. Minimal postoperative complications accompanied by ulcer healing and relief of lower extremity symptoms were achieved for all the patients, underscoring the important role of incompetent perforator veins in the formation of chronic venous insufficiency.

Intussusception in adults.

Intussusception in adults is a rare entity that it is generally caused by definable intraluminal pathology. We report four cases of adult intussusception caused by lymphoma of the terminal ileum (2), an inflamed appendix (1) and a mucosal polyp (1). All presented with a variety of nonspecific and chronic symptoms, including abdominal pain, nausea and vomiting, consistent with partial small bowel obstruction. Only one patient had palpable masses in the abdomen. The most useful diagnostic radiological method was computed tomography (CT), which showed "target" lesions. The presence of the characteristic "target" lesion may obviate the need for further studies, including a barium enema. As in the cases reported here, treatment involves more than simple reduction; surgical resection is usually indicated.

ZD9583, an orally effective thromboxane A2 synthase inhibitor and receptor antagonist with a sustained duration of action in rat and dog.

The thromboxane A2 (TXA2) synthase inhibitory activity and the TXA2 receptor (TP-receptor) blocking action of ZD9583 ((4Z)-6-[(2S,4S,5R)-2-(1-[2-cyano-4-methylphenoxy]-1-methylethyl) -4-(3-pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid) has been evaluated in-vitro by use of whole blood and platelets from man, and ex-vivo by use of platelets and whole blood from rats and dogs. ZD9583 caused concentration-dependent inhibition of human platelet microsomal TXA2 production with an IC50 of 0.017 +/- 0.003 microM; this inhibition was associated with an increase in prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) formation. ZD9583 also inhibited collagen-stimulated TXA2 synthesis in whole blood from man, rat and dog giving IC50 values of 0.027 +/- 0.005, 0.02 +/- 0.006 and 0.013 +/- 0.01 microM, respectively. The drug did not modify platelet cyclooxygenase activity as inhibition of thromboxane B2 (TXB2) formation was associated with a concomitant increased synthesis of prostaglandin D2 (PGD2), PGE2 and PGF2 alpha. ZD9583 had little effect on cultured human umbilical vein endothelial cell prostacyclin synthase giving an IC50 of 24.2 +/- 4.9 microM. In-vitro ZD9583 caused concentration-dependent inhibition of U46619-induced aggregation responses of platelets from man, rat and dog, yielding apparent log A2 values of 8.7 +/- 0.12, 8.8 +/- 0.2 and 9.3 +/- 0.2, respectively. The drug was selective; at concentrations up to 100 microM it did not affect 5-hydroxytryptamine or the primary phases of adenosine diphosphate and adrenaline-induced aggregation. ZD9583 (100 microM) did not, furthermore, modify the platelet inhibitory effects of PGD2, prostaglandin E1 (PGE1) and prostacyclin. Oral administration of ZD9583 (3-10 mg kg-1) to both rats and dogs caused dose-dependant inhibition of collagen-stimulated TXA2 production ex-vivo which persisted for up to 12 h. The drug also caused profound TXA2 receptor blockade in both species for in excess of 12-h after an oral dose of 3 mg kg-1. ZD9583 (3 mg kg-1, p.o.), when administered to dogs over a five-day period at 12 h intervals, did not cause either tachyphylaxis or an accumulation of effect. We conclude that ZD9583 is a potent, selective, orally active thromboxane synthase inhibitor and TXA2 receptor antagonist.

ZD1542, a potent thromboxane A2 synthase inhibitor and receptor antagonist in vitro.

1. The thromboxane A2 synthase (TXS) inhibitory activity and the thromboxane A2 (TP)-receptor blocking action of ZD1542 (4(Z)-6-[2S,4S,5R)-2-[1-methyl-1-(2-nitro-4-tolyloxy)ethyl]-4-(3- pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid) has been evaluated in vitro on platelets and whole blood from a range of species including man. Antagonist activity has also been investigated in vascular and pulmonary smooth muscle preparations in vitro. 2. ZD1542 caused concentration-dependent inhibition of human platelet microsomal thromboxane B2 (TXB2) production in vitro (IC50 = 0.016 microM); this inhibition was associated with an increase in prostaglandin E2 (PGE2) and PGF2 alpha formation. 3. ZD1542 also inhibited collagen-stimulated TXS in human, rat and dog whole blood giving IC50 values of 0.018, 0.009 and 0.049 microM respectively. The drug did not modify platelet cyclo-oxygenase activity as inhibition of TXB2 formation was associated with a concomitant increase in the levels of PGD2, PGE2 and PGF2 alpha. ZD1542 had little if any effect against cultured human umbilical vein endothelial cell (HUVEC) cyclo-oxygenase (IC50 > 100 microM) and prostacyclin (PGI2) synthase (IC50 = 18.0 +/- 8.6 microM). 4. ZD1542 caused concentration-dependent inhibition of U46619-induced aggregation responses of human, rat and dog platelets yielding apparent pA2 values of 8.3, 8.5 and 9.1 respectively. The drug was selective as, at concentrations up to 100 microM, it did not modify 5-hydroxytryptamine (5-HT) or the primary phases of adenosine diphosphate (ADP) and adrenaline-induced aggregation. Furthermore, ZD1542 (100 microM) modified only weakly the platelet effects of PGD2, PGE1 and PGI2. 5. ZD1542 also caused concentration-dependent inhibition of U46619-mediated contractions of rat thoracic aorta, guinea-pig trachea and lung parenchyma preparations giving apparent pA2 values of 8.6,8.3 and 8.5 respectively. At concentrations approaching three orders of magnitude greater than those required to block U46619-mediated contractions, the drug did not affect the actions of non-prostanoid agonists or exhibit agonist activity in any of the smooth muscle preparations employed; neither did it interact at EP- or FP-receptors.6. In conclusion, the present study demonstrates that ZD1542 is a drug that exhibits both potent,selective TXS inhibition and TXA2 receptor antagonism.