The relative importance of thrombin inhibition and factor Xa inhibition to the antithrombotic effects of heparin

The relative importance of antithrombin and anti-factor Xa activities of heparin fractions required to achieve optimal antithrombotic effects is unknown. To study this, we measured the effects of standard heparin, an octasaccharide heparin fraction (anti-factor Xa activity only), and dermatan sulfate (antithrombin activity only) on the prevention of thrombosis and related this to their anticoagulant effects in vivo in rabbits. Thrombosis was measured as the incorporation of 125I- fibrinogen into tissue thromboplastin-induced thrombi using a Wessler- type model. Ex vivo changes in thrombin clotting time (TCT) were used as an index of antithrombin activity, and a chromogenic anti-factor Xa assay was used to measure anti-factor Xa activity. In addition, the ability of the three sulfated polysaccharides to simultaneously inhibit the generation of thrombin activity and to enhance the inactivation of the factor Xa added to initiate thrombin generation in plasma was determined. Standard heparin, in a dose of 10 anti-factor Xa U/kg, inhibited thrombus formation by 90%, prolonged the TCT by two seconds, and resulted in an anti-factor Xa level of 0.32 U/mL. The octasaccharide heparin fraction, in a dose of 10 anti-factor Xa U/kg, inhibited thrombus formation by 41%, had no effect on the TCT, and resulted in an anti-factor Xa level of 0.28 U/mL. Higher doses of the octasaccharide resulted in a further increase in the anti-factor Xa levels but had no further effect on thrombus formation. Dermatan sulfate, in a dose of 500 micrograms/kg, inhibited thrombus formation by 95%, but had no affect on the TCT. These results indicate that the antithrombotic effect achieved by inhibiting factor Xa is limited and that better antithrombotic effects are achieved by heparin or heparin- like substances capable of influencing the inactivation and/or the generation of thrombin.     

The use of intraoperative ultrasound in laparoscopic adrenal surgery

Background: Laparoscopic adrenalectomy has been shown to be a safe and effective therapy for benign adrenal lesions. We review our experience with this procedure, including the use of laparoscopic ultrasound. Methods: We retrospectively reviewed our experience with 36 patients who underwent resection of 42 adrenal glands. Data gathered included preoperative evaluation and diagnosis, operative time, blood loss, complications, and follow-up status. Laparoscopic ultrasound was used to guide dissection and characterize a variety of adrenal lesions. Results: Thirty-five of 36 patients underwent successful laparoscopic adrenalectomy. There was one conversion to the open procedure in a patient with bilateral adrenal metastases from an endometrial cancer. For the bilateral laparoscopic procedure, the operative time averaged 262 mins, blood loss was 160 cc, and hospital stay was 3.0 days. For unilateral cases, operative time averaged 193 min, blood loss was 108 cc, and hospitalization was 1.1 days. Six patients experienced perioperative complications, most of which were minor and transient. Laparoscopic ultrasound was useful to define anatomy and to identify the adrenal vein, especially on the left side. Conclusions: Laparoscopic adrenalectomy is the procedure of choice for benign adrenal disease. Laparoscopic ultrasound is useful to localize and aid in the dissection of the left adrenal vein. Received: 24 December 1998/Accepted: 12 February 1999     

小儿淋巴管瘤的MRI诊断

目的分析小儿淋巴管瘤的磁共振表现及其病理基础。方法对６例经手术病理证实的、年龄７天至７岁的小儿淋巴管瘤患者的磁共振表现进行回顾性分析。结果淋巴管瘤磁共振表现为Ｔ１ＷＩ上呈与肌肉相似或稍高的信号，Ｔ２ＷＩ上高于脂肪信号。５例瘤内可见低信号分隔，１例瘤内见血管流空影，３例见明显包膜，３例边界不清。２例病理诊断为海绵状淋巴管瘤，４例诊断为囊状淋巴管瘤。结论磁共振成像可较好地显示肿瘤的大小、形态及范围，从而指导手术治疗。     

Antihypertensive drugs, dietary salt, and renal protection: how low should you go and with which therapy?

Although it is clear that hypertension accelerates the rate of progression of most forms of chronic renal disease, many unanswered questions remain concerning how to optimally preserve kidney function in patients with hypertension and renal insufficiency. The mechanisms by which hypertension accelerates progression of renal disease have been extensively studied in experimental models. Glomerular capillary hypertension, consequent to an increase in systemic blood pressure combined with a reduction in preglomerular resistance and/or an increase in postglomerular resistance, results in increased hydraulic stress to the glomerular capillary wall. This and other mechanisms result in the release of growth-promoting cytokines and soluble mediators of fibrosis that stimulate cellular proliferation and matrix accumulation, ultimately leading to glomerular sclerosis and interstitial fibrosis. Almost without exception, studies in animals demonstrate that blood pressure reduction reduces the rate of progression of experimental renal disease. Angiotensin-converting enzyme inhibitors and, possibly, calcium antagonists may have a therapeutic advantage compared with other antihypertensive drugs in preventing kidney damage. This has been linked to both blood pressure-dependent and -independent actions. However, most experimental studies have failed to reduce blood pressure to a level sufficient to establish the clinical relevance of potential blood pressure-independent effects. Experimental studies comparing various types of antihypertensive drugs in which a mean arterial pressure (MAP) of approximately 92 mm Hg is achieved are necessary to determine whether clinically important differences in the effects of these drugs on the rate of progression of renal disease exist. Clinical experience with high blood pressure and kidney disease in humans suggests that the risk of developing hypertension-associated renal disease is a continuous variable across the entire range of systolic and diastolic blood pressures. Logically, optimal protection of kidney function may therefore be a continuous function of declining systemic blood pressure. Consistent with this view, recent clinical trials suggest that reducing MAP to 92 mm Hg, corresponding to a blood pressure reading of 125/75 mm Hg, provides more optimal stabilization of renal function in patients with nondiabetic proteinuric kidney disease (>1 g/d) compared with more conventional therapy with a blood pressure goal of 140/90 mm Hg (MAP 107 mm Hg). Clinical trials in patients with diabetes mellitus and renal insufficiency also demonstrate the benefits of reducing blood pressure to approximately 95 mm Hg MAP. Dietary salt consumption may be another important variable affecting the rate of progression of renal disease due to both direct, salt-dependent effects on renal growth and the action of decreased salt intake to augment the antihypertensive and antiproteinuric properties of many drugs. The precise role of alterations in dietary salt consumption on progression of renal disease directly as well as on the effectiveness of various antihypertensive drugs has yet to be examined in clinical trials.     

Staged repair of giant omphalocele in the neonatal period

Background/Purpose

The aim of this study was to analyze the outcome of giant omphalocele repaired in the neonatal period.

Methods

Twelve consecutive (1997-2004) neonates with giant omphalocele (defect >6 cm with liver herniation) were reviewed. A silo of Prolene mesh (Ethicon) was attached to the fascia and the defect was closed without opening the amniotic sac after sequential reduction. In 2 neonates with ruptured omphalocele a plastic sheet was inserted below the mesh. Data are reported as median and range.

Results

Gestational age was 38 weeks (range, 32-40 weeks) and birth weight was 2.9 kg (range, 1.0-3.1 kg). The final closure was achieved at 26 days (range, 16-62 days). Three neonates (25%) died before final closure (causes: ruptured omphalocele, lung hypoplasia, cardiac anomalies, and intestinal failure). In the 9 surviving neonates, mechanical ventilation was required for 8 days (range, 2-20 days), hospital stay was 42 days (range, 23-73 days), and full enteral feeding was achieved on day 12 (range, 4-53 days). Complications included wound infection in 5 neonates and midgut volvulus in 1. Prophylactic Ladd's procedure was performed laparoscopically at a later stage in 4 children. At laparoscopy, intraperitoneal adhesions were minimal and the central liver did not preclude the operation. The 9 survivors are all well after 46 months (range, 12-67 months).

Conclusions

Giant omphalocele can be safely repaired in the neonatal period without opening the amniotic sac. Intestinal malrotation should be excluded and Ladd's procedure can be performed laparoscopically at a later stage.     

Subareolar and peritumoral injection identify similar sentinel nodes for breast cancer

Background Sentinel lymph node (SLN) mapping with radioisotope and blue dye is rapidly becoming the standard of care for breast cancer. The optimal location for injection of radioisotope and blue dye is still being investigated. The goal of this study was to determine whether blue dye injection into the subareolar (SA) location localized the same sentinel nodes as the peritumoral (PT) location for patients with breast cancer. Methods Three hundred thirty-two patients with biopsy-proven operable breast cancer or ductal carcinoma in situ at two institutions underwent SLN mapping. Eighty-three patients had PT injection of blue dye (group 1), and 249 patients had SA injection of blue dye (group 2). All patients underwent PT injection of^99mTc-labeled sulfur colloid. Results The two groups were similar in age, previous biopsy type, and tumor size, location, and histology. The mean number of SLNs identified was 2.4 (range, 0–9) in group 1 and 2.5 (range, 0–11) in group 2. The SLN identification rate was 95% for group 1 and 97% for group 2. The isotope success rate was 94% for both groups. The blue dye success rate was 84% for group 1 and 90% for group 2. The isotope/blue dye concordance rate was 87% for group 1 and 90% for group 2. At a median follow-up of 28 months (range, 14 to 40), there were no axillary recurrences in any of the 332 patients. Conclusions These data suggest that delivery of mapping reagents in the SA and PT locations identifies similar lymph nodes. Because of simplicity and the similarity in node identification between SA and PT injection, further investigation of the SA site for delivery of SLN mapping reagents for breast cancer is warranted. Presented at the 54th Annual Cancer Symposium, Society of Surgical Oncology. Washington, DC, March 15–18, 2001.     

Leptin and prostate cancer

BACKGROUND: Higher prostate cancer mortality rates among US immigrants from countries with lower rates suggest environmental influences on prostate carcinogenesis (e.g., diet, body composition). METHODS: In a study identifying determinants of clinically relevant prostate cancer, we compared plasma concentrations of leptin, an adiposity-related hormone, in 48 men with tumors 0.5 cc in volume or with histologic evidence of extraprostatic extension but without metastases ("high-volume disease"), matched by age (+/- 5 years) and year at diagnosis (+/- 1 year). RESULTS: Men with high-volume disease exhibited higher leptin concentrations overall and after stratification by age, testosterone level, height, and body mass index (BMI). Analysis revealed that men with elevated leptin concentrations had an increased risk of diagnosis with high-volume disease (odds ratio (OR) = 2.35, 95% confidence interval (CI) = 1.01-5.44), as did men with high leptin and high testosterone (OR = 9.73, 95% CI = 2.05-46.24) and men >/=5'8" with high leptin (OR = 3.67, 95% CI = 1.40-9.63). CONCLUSIONS: Leptin may affect the risk of clinically relevant prostate cancer through testosterone and factors related to stature and obesity.