Long-term kidney graft survival across a positive historic but negative current sensitized cross-match

BACKGROUND: The sensitive cross-match (XM) techniques that have been introduced for clinical transplantation can detect anti-donor immune reactivity despite a negative standard National Institute of Health (NIH) cross-match. One of them uses anti-kappa human light chain globulins (AHG). But there is some discussion about the clinical consequences of a positive AHG-XM in the historical sera that became negative in the sera collected just before the transplantation (pretransplant sera). This study was intended to assess the risk of kidney graft failure associated with a positive historic but negative pretransplant AHG-XM in allosensitized patients having a negative historic NIH-XM. METHODS: This retrospective study includes 90 consecutive renal transplants in immunized patients performed at one center between 1985 and 1991. All of the patients had negative historical and pretransplant standard NIH lymphocytotoxic cross-matches and received the same immunosuppressive regimen. The AHG-XMs were done retrospectively using peak historic and sera collected on the day of the transplantation. RESULTS: The AHG cross-match (AHG-XM) was positive in 17 patients, although the standard NIH cross-match was negative. Fourteen of them had a positive historical but negative pretransplant AHG-XM. The actuarial graft survival in this group of 14 patients was 100% at 1 year and 78% at 9 years compared with 90 and 67%, respectively, in patients with negative historical AHG-XM. In addition, the number of rejection episodes per patient as well as renal function at 1, 2, and 5 years were similar in the two groups. IgG anti-donor HLA class I accounted for the XM positivity in 12 of the 14 patients; most rapidly lost all antibody reactivity by NIH technique in an average time of 8 months before the transplantation. In conclusion, this study suggests that transplant patients having a negative historic NIH-XM but a positive historic AHG-XM may not be at high risk of graft failure especially if there is a well-documented sera history showing a marked decrease in PRA level before transplantation and a negative pretransplant AHG-XM.     

Denosumab and bisphosphonates: different mechanisms of action and effects

To treat systemic bone loss as in osteoporosis and/or focal osteolysis as in rheumatoid arthritis or periodontal disease, most approaches target the osteoclasts, the cells that resorb bone. Bisphosphonates are currently the most widely used antiresorptive therapies. They act by binding the mineral component of bone and interfere with the action of osteoclasts. The nitrogen-containing bisphosphonates, such as alendronate, act as inhibitors of farnesyl-pyrophosphate synthase, which leads to inhibition of the prenylation of many intracellular signaling proteins. The discovery of RANKL and the essential role of RANK signaling in osteoclast differentiation, activity and survival have led to the development of denosumab, a fully human monoclonal antibody. Denosumab acts by binding to and inhibiting RANKL, leading to the loss of osteoclasts from bone surfaces. In phase 3 clinical studies, denosumab was shown to significantly reduce vertebral, nonvertebral and hip fractures compared with placebo and increase areal BMD compared with alendronate. In this review, we suggest that the key pharmacological differences between denosumab and the bisphosphonates reside in the distribution of the drugs within bone and their effects on precursors and mature osteoclasts. This may explain differences in the degree and rapidity of reduction of bone resorption, their potential differential effects on trabecular and cortical bone, and the reversibility of their actions.     

Endoscopic subfascial surgery for incompetent perforator veins in patients with active venous ulceration

Background: Previously, subfascial ligation of perforator veins to treat venous ulceration in the lower extremities required long skin incisions through diseased skin and subcutaneous tissue. This was known as "the Linton operation." In 1985, Hauer described an endoscopic technique for ligating incompetent perforator veins; this seminal contribution marked the advent of subfascial endoscopic perforator surgery (SEPS). Methods: From 1996 to 1998, we prospectively collected data on 41 patients with chronic venous insufficiency (CVI) who underwent a SEPS procedure at our institution. Preoperative assessment consisted of color-flow duplex ultrasound scanning, as well as ascending and descending phlebography. Results: Some 45 SEPS procedures were performed on the 41 patients. Ages ranged from 42 to 84 years (mean, 60). Active venous ulcers were present in 37 legs; healing occurred within 9 weeks in 33 of them. No new ulcers developed in the follow-up period, a mean of 44 weeks. Conclusion: The results suggest that the SEPS procedure incorporated into the overall treatment plan for patients with CVI produces active healing with a minimum of postoperative complications. The study demonstrates the safety and efficiency of this procedure; it also underscores the important role incompetent perforator veins have in the formation of venous ulcers.     

Endoscopic transmural entry into pancreatic fluid collections using a dedicated aspiration needle without endoscopic ultrasound guidance: success and complication rates

BACKGROUND: Endoscopic drainage of pancreatic fluid collections (PFC) is performed with increasing frequency. A variety of techniques for performing transmural entry have been described. However, data are lacking on the technical success and safety of transmural entry using a single technique. The authors describe the largest experience in transmural entry of PFCs without endoscopic ultrasound (EUS) guidance using a dedicated aspiration needle. METHODS: All patients who underwent endoscopic transmural drainage of PFC from October 1998 to May 2006 were identified from the endoscopy database. Data were abstracted from the endoscopic procedure report and the patient records then placed in a JMP drive. All drainages were performed without EUS guidance after visualization of an obvious intraluminal bulge using a dedicated large-bore aspiration needle. The transmural tract into the PFC was dilated using a balloon with a diameter of 6 to 20 mm followed by subsequent placement of one or two 10-Fr double pigtail stents with or without nasocystic irrigation tubes. Successful entry was defined as entry allowing for the placement of stents. RESULTS: No significant difference in the complication rates was observed when they were analyzed for the following variables: age, gender, balloon diameter, presence of endoscopic impression, drainage approach, and size and type of fluid collection. CONCLUSION: Endoscopic transmural drainage of pancreatic fluid collections can be performed safely and effectively via the Seldinger technique without endoscopic ultrasound guidance. The study data will allow sample size calculations to be made if direct comparisons with this technique and others are undertaken.     

Development and Testing of a Field Diagnostic Assay for Peste des Petits Ruminants Virus

We have developed an immunochromatographic test for the diagnosis of peste des petits ruminants (PPR) under field conditions. The diagnostic assay has been tested in the laboratory and also under field conditions in Ivory Coast, Pakistan, Ethiopia and Uganda. The test is carried out on a superficial swab sample (ocular or nasal) and showed a sensitivity of 84% relative to PCR. The specificity was 95% over all nasal and ocular samples. The test detected as little as 10³ TCID₅₀ (50% tissue culture infectious doses) of cell culture‐grown virus, and detected virus isolates representing all four known genetic lineages of peste des petits ruminants virus. Virus could be detected in swabs from animals as early as 4 days post‐infection, at a time when clinical signs were minimal. Feedback from field trials was uniformly positive, suggesting that this diagnostic tool may be useful for current efforts to control the spread of PPR.     

Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes

Endothelial dysfunction reflects an imbalance of vasodilators and vasoconstrictors. Endogenous endothelin activity seems to be increased in human obesity and type 2 diabetes, and cellular studies suggest that this factor may itself reduce bioavailable nitric oxide (NO). We studied 20 lean, 20 obese, and 14 type 2 diabetic individuals under three protocols, measuring leg vascular responses to intra-arterial infusions of NG-monomethyl-l-arginine (l-NMMA; an inhibitor of NO synthase) alone or in combination with BQ123 (an antagonist of type A endothelin receptors) or phentolamine (used as a control vasodilator). NO synthase inhibition alone (study 1) produced an approximately 40% increase in leg vascular resistance (LVR) in all three participant groups, which was not statistically different across groups (increase in LVR: lean, 135 +/- 28; obese, 140 +/- 32; type 2 diabetic, 184 +/- 51 units; NS). By design, BQ123 at the infused rate of 3 micromol/min produced equivalent approximately 35% reductions in LVR across groups. The subsequent addition of l-NMMA produced a greater increase in LVR among obese participants than lean or type 2 diabetic participants (study 2: lean, 182 +/- 48; obese, 311 +/- 66; type 2 diabetic, 186 +/- 40; P = 0.07). Compared with study 1, the effect of l-NMMA was magnified by BQ123 in obese participants but not in lean or type 2 diabetic participants (P = 0.005, study 1 vs. 2; P = 0.03 for group effect). Phentolamine (75 mg/min) produced vasodilation in obese participants comparable to that seen with BQ123 but failed to augment the L-NMMA response. Endothelin antagonism unmasks or augments NO synthesis capacity in obese but not type 2 diabetic participants. This suggests that impaired NO bioavailability as a result of endogenous endothelin may contribute to endothelial dysfunction in obesity, in addition to direct vasoconstrictor effects of endothelin. In contrast, endothelin antagonism alone is insufficient to restore impaired NO bioavailability in diabetes.     

Pneumothorax after left pneumonectomy: implantation of an intrapleural prosthesis

Postpneumonectomy syndrome is defined as an airway obstruction due to mediastinal shift and rotation after pneumonectomy. A patient who had undergone a left pneumonectomy for bronchial carcinoma 13 years before presented with tension pneumothorax of her remaining lung. Although all factors relevant to the development of postpneumonectomy syndrome were ascertained, the patient had a pneumothorax rather than an airway obstruction. This pneumothorax was treated surgically. The goal of this operation was to reduce the right pleural cavity volume by implanting an intrapleural prosthesis in the pneumonectomy cavity. This treatment is identical to that used for postpneumonectomy syndrome, which allows the right lung to be rejoined with the thoracic wall.     

Contribution of left ventricular contraction to the generation of right ventricular systolic pressure in the human heart

To determine whether left ventricular (LV) contraction contributes to the generation of right ventricular (RV) systolic pressure in humans, LV and RV pressures and their first derivative (dP/dt) were recorded simultaneously with micromanometer-tipped catheters in 11 conscious subjects. Seven subjects had normal LV and coronary angiograms. Four subjects had moderate LV dysfunction (resting ejection fraction 0.40 to 0.50), and three of these had coronary artery disease. During normal sinus rhythm, LV contraction slightly preceded RV contraction (mean 20 msec), and LV and RV dP/dt recordings showed single positive systolic peaks that were coincident. During endocardial pacing of the RV free wall, RV contraction preceded LV contraction (mean 23 msec) and two systolic RV dP/dt peaks were recorded, the first (peak I) occurring significantly before (mean +/- SD = 67 +/- 23 msec, p less than .01), and the second (peak II) coincident with the single systolic LV dP/dt peak. RV ectopic beats produced a similar RV dP/dt pattern, with peak I occurring 63 +/- 11 msec (p less than .01) before, and peak II coincident with the single LV dP/dt peak. Conversely, during LV ectopic beats, LV contraction preceded RV contraction (mean 63 msec) and two systolic RV dP/dt peaks were recorded, but peak I was coincident with the single LV dP/dt peak, while peak II occurred significantly later (63 +/- 26 msec, p less than .01). In two subjects right bundle branch block produced similar findings. In three subjects left bundle branch block produced little ventricular asynchrony (mean 14 msec), but did delay the development of peak LV dP/dt after LV contraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Basal, sham feed and pentagastrin stimulated gastric acid, pepsin and electrolytes after omeprazole 20 mg and 40 mg daily.

Gastric secretion was measured in nine patients with duodenal ulcer before, and after treatment for four weeks with omeprazole 20 mg or 40 mg daily. Basal acidity and acid output were affected variably by 20 mg, but inhibited totally by 40 mg daily. Sham feed stimulated acid output was reduced by 20 mg daily and completely inhibited by 40 mg daily. Maximal pentagastrin stimulated acid output was halved by 20 mg omeprazole daily and 84% inhibited by 40 mg daily. The reduction in acidity was always greater than the reduction of volume. Pepsin output after pentagastrin was little altered but with the reduced secretory volume pepsin concentrations were increased by both doses. The major cause of reduced aspirate acid output after omeprazole is decreased secretion of the primary acid component of the parietal cell by the proton pump H+K+ ATPase. Duodenogastric alkaline reflux is, however, markedly increased after omeprazole and is an additional factor in the resultant hypoacidity or even anacidity after this drug.