Involvement of platelet activating factor and thromboxane A2 in the renal response to unilateral ureteral obstruction

Platelet activating factor (PAF) and thromboxane A2 (TxA2) are two vasoactive mediators which can decrease renal blood flow. Both are synthesized by various intrarenal cell types or by macrophages which may infiltrate the kidney during unilateral ureteral obstruction (UUO). In several experimental systems, PAF receptor activation is accompanied by TxA2 release; pharmacological modification of TxA2 synthesis or receptor activation modulates the response to PAF. The involvement of PAF in UUO has not been studied previously, and the role of TxA2 has not been clearly defined by previous investigations. The hemodynamic response to acute UUO is characterized by decreases in renal blood flow (RBF) and glomerular filtration rate and an acute increase in ureteral pressure. In the present experiments, the involvement of either PAF or TxA2 in the acute response to UUO was studied by determining if blockade of either the TxA2 or PAF receptor would affect the renal hemodynamic response to UUO. In addition, the effect of blockade of the TxA2 receptor on the renal response to PAF was determined. Our results indicate that only a small portion of the renal response to PAF is mediated by TxA2, and that neither PAF nor TxA2 can be implicated in the acute hemodynamic response to UUO. TxA2 or PAF involvement in the chronic response to UUO still remains to be determined.     

Heart rate and blood pressure variability as markers of sensory blockade with labour epidural analgesia

PURPOSE: To evaluate the correlation between the progression of somatosensory blockade and changes in autonomic outflow following the onset of labour epidural analgesia. METHODS: Twelve labouring parturients consented to participate in the study. Baseline electrocardiogram, blood pressure (BP) and respiratory rate were recorded for ten minutes. The epidural consisted of 0.125% bupivacaine with 50 microg of fentanyl (total volume 20 mL). Measurements were repeated for ten minutes after initiation of the block. The level of sensory block was measured bilaterally with loss of sensation to ice at two-minute intervals. Wavelet transform was used to obtain heart rate (HR) and BP variability every two minutes following the loading dose of epidural medication. High frequency power of HR variability was used to assess changes in parasympathetic activity. The total power of BP variability was used to assess changes in sympathetic activity. A nonparametric repeated measures ANOVA was used for the variability data, and a Spearman rank correlation test was used to evaluate the relationship between the sensory block and HR and BP variability. RESULTS: The sensory block progressed to T9 at ten minutes post-epidural and was the mirror image of the decrease in total power of BP variability. High frequency power of HR variability increased to a plateau at six minutes post-epidural. A significant correlation was found between the increase in sensory block and the observed decrease in BP variability (r = -1.000, P = 0.0028). CONCLUSION: In this study of labouring parturients, BP variability correlated with the progression of both sympathetic and somatosensory block following epidural anesthesia, while HR variability was shown to be a surrogate marker of increased parasympathetic activity.     

Carotid intima-media thickness, carotid wall shear stress and restenosis after femoro-popliteal percutaneous transluminal angioplasty (PTA).

OBJECTIVE: To determine the relationship between carotid intima-media thickness (IMT), carotid wall shear stress (WSS) and restenosis after femoro-popliteal percutaneous transluminal angioplasty (PTA). PATIENTS AND METHODS: Thirty-one subjects (18 men, 13 women, median age 69 years) treated with femoro-popliteal PTA for symptomatic peripheral arterial occlusive disease were enrolled. On admission, IMT, internal diameter and blood velocity of the common carotid artery (CCA) were assessed by high-resolution ultrasonography. Blood viscosity was measured and carotid WSS was calculated. Patients were followed up for 6 months for the occurrence of significant restenosis (>50%) as documented by duplex ultrasonography. Two patients were lost to follow-up. RESULTS: Fourteen patients (48%) developed restenosis at 6 months. IMT and WSS were not different in patients without and with restenosis (IMT: 0.90 (0.85-0.97) vs. 0.89 (0.84-0.93) mm, p = 0.51; WSS: 14.1 (11.9-19.2) vs. 15.9 (12.8-21.5) dyne/cm2, p = 0.48). The hazard ratio of incident restenosis as estimated by Cox regression analysis was 0.04 for IMT (p = 0.23; 95% CI 0.0001-8.22) and 1.07 for WSS (p = 0.10; 95% CI 0.98-1.17). CONCLUSIONS: In this pilot study involving a limited number of patients, carotid IMT and carotid WSS are not significantly related to restenosis at 6 months after femoro-popliteal PTA. This might be the result of different underlying pathophysiology for atherosclerosis and restenosis.     

Chronic delta hepatitis in haemophiliacs

The seroepidemiological profile of HBV and HDV was investigated in 640 male haemophiliacs. Twenty-seven of forty-four HBsAg carriers were anti-HDV-IgG positive, 22 were also anti-HDV-IgM positive. A markedly lower prevalence of HDV infection was found in patients with anti-HBc in the absence of HBsAg and anti-HBs (6/41). Repeated detection of anti-HDV-IgM in 5/41 individuals of this group indicates that circulating HBsAg is not an absolute prerequisite for chronic HDV infection. Overall, chronically active HDV infection was detected more frequently in quiescent than in active chronic HBV infections. Anti-HDV-IgM was not detected in the absence of anti-HDV-IgG antibodies. Anti-HDV-IgG may disappear after resolution of HDV infection, as indicated by the low prevalence (1/42) in such individuals with past HBV infection as well as by loss of anti-HDV-IgG observed in two patients.     

Chondrocyte nonresponsiveness of arthritic articular cartilage caused by short term immobilization

We studied the effect of short term immobilization on chondrocyte synthetic function. Arthritis from intraarticular injection of either glucose oxidase or interleukin 1 (IL-1) led to suppression of proteoglycan synthesis. Extension casting of arthritic knees prevented inhibition of proteoglycan synthesis, whereas later casting restored synthesis to normal. During chronic antigen induced arthritis casting protected chondrocyte synthesis for a period of 5 days. The chondrocyte nonresponsiveness was not from altered penetration of suppressing substances. Radiolabelled biologically active IL-1 showed no difference in retention or localization in articular cartilage of either mobile or immobile knees. Flexion casting did not induce unresponsiveness of chondrocytes and suppression of synthesis was similar to that in mobile arthritic knees, indicating the importance of loading. The nonresponsiveness occurred only during immobilization and rapidly disappeared after removal of the cast, provided that suppressing agents were still present. Thus, during short term immobilization chondrocytes are protected from inhibition of proteoglycan synthesis by suppressing agents. This protection may benefit repair of the depleted cartilage matrix with waning inflammation.     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Enhancement of spontaneous fibrinolytic activity in diabetic retinopathy.

The fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.     

Quantification of flow through an interatrial communication. Application to the partial Fontan procedure.

The partial Fontan procedure has become an accepted alternative for the high-risk candidate. Creation of a small right-to-left shunt will lower the systemic venous pressure and improve systemic cardiac output while maintaining an acceptable systemic arterial saturation. However, because of variations in patient size and postoperative transpulmonary gradient, proper sizing of the residual defect is difficult. We have therefore conducted a series of experiments on a model that simulates the blood flow across interatrial defects of varying sizes at several pressure gradients. We used porcine blood to develop guidelines for the sizing of the residual defect. Our results demonstrate a linear relationship between flow and pressure gradient across all hole sizes tested. In addition, there was a linear relationship between atrial septal defect size and flow at each pressure gradient. Our data show that the Gorlin formula predictions overestimated flow by 10% to 40%. It is evident from these data that relatively small changes in the size of the atrial septal defect or in the pressure gradient result in significant changes in flow. Therefore we advocate the use of an adjustable interatrial communication such as the snare-controlled adjustable atrial septal defect for patients undergoing partial Fontan procedures.     

Rupture of the posterior tibial tendon: CT and surgical findings

Computed tomography (CT) was performed in 42 patients with 49 clinically suspected tears of the posterior tibial tendon. Twenty-eight of the 49 suspected tears were subsequently surgically explored and repaired. Three patterns of tendon abnormalities were recognized on CT scans: type I-intact, hypertrophied, heterogeneous tendon; type II-attenuated tendon; and type III-absence of a portion of a tendon. Types I and II correlated with partial rupture seen during surgery, and type III correlated with complete rupture of the tendon. CT findings were accurate in 96% of the patients who underwent surgery. In four cases (14%), tendon rupture was seen on CT scans, but the extent of the injury was underestimated and the rupture was misclassified. Reactive periostitis of the distal tibia was seen in 71% of diseased tendons and may represent an important factor in the diagnosis of tendon rupture.