alpha-Adrenoceptor subtypes in isolated corporal tissue from patients undergoing gender re-assignment

OBJECTIVE: To investigate the pharmacology and functionality of alpha(1)-adrenoceptors in human corpus cavernosum, and to determine the predominant subtype. MATERIALS AND METHODS: Cavernosal tissue specimens were obtained from the penises of 22 men (mean age 37.4 years) removed during gender re-assignment surgery. The men had been maintained on long-term oestrogen therapy before surgery, to aid the development of secondary feminine characteristics (oestrogen treatments were stopped 6 weeks before surgery). Corpus cavernosum strips were mounted in organ baths perfused with Krebs' solution. A control concentration-response curve (CRC) to phenylephrine (a nonselective alpha(1)-agonist) was obtained. Then the tissues were incubated with the alpha(1A) antagonist, WB4101; the alpha(1B) antagonist, chloroethylclonidine; or the alpha(1D) antagonist BMY 7378 (all at 1 microm) and the CRC to phenylephrine was repeated. The concentration producing a half-maximal response (EC(50)) and pK(B) values (logarithm of the dissociation constant, a measure of affinity) were determined. RESULTS: WB4101 produced a parallel rightward shift of the CRC to phenylephrine, with a pK(B) of 7.49. BMY 7378 also produced a parallel rightward shift of the CRC to phenylephrine with a pK(B) of 6.45. Chloroethylclonidine had a similar effect on the phenylephrine CRC, with a pK(B) of 5.90. CONCLUSION: Alpha(1)-adrenoceptors in human cavernosal tissue have a relatively low affinity for BMY 7378 and chloroethylclonidine, but are more sensitive to WB4101. This confirms that the predominant alpha(1)-adrenoceptor subtype in human corpus cavernosum is the alpha(1A) subtype and this might help in developing more selective antagonists and agonists for managing erectile dysfunction and priapism.     

Obesity increases the likelihood of total joint replacement surgery among younger adults

We conducted a retrospective review of medical charts of patients, aged 18 to 59 years old, who underwent either a total knee replacement (TKR) or total hip replacement (THR) from January 2002 to December 2004. Of the 204 study subjects, 52% had a TKR while 48% had a THR. Obesity was significantly associated with the need for a TKR or THR when comparing the study group to adults of similar age in the general population (P< 0.0001). Seventy-two percent (146) of the study group was obese and 21% (42) overweight (BMI 25.0 to 29.9 kg/m(2)) compared to only 26% (596) obese and 34% (732) overweight in the general population. Patients undergoing a TKR were significantly more likely to be obese (BMI>30 kg/m(2)) than those having a THR, 83% (89) compared to 59% (57) (P< .0006). Our findings support those previously observed in the elderly population. Primary and secondary prevention programs aimed at reducing obesity are strongly recommended.     

Lipoprotein(a) levels in relation to albumin concentration in childhood nephrotic syndrome.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a lipoprotein consisting of a low-density lipoprotein (LDL) particle linked to a polymorphic glycoprotein, apoprotein(a) [apo(a)]. Prior studies have reported high Lp(a) levels in the nephrotic syndrome, but it is still controversial whether this is due to the degree of hypoalbuminemia or proteinuria. METHODS: To investigate a model of nephrotic syndrome in the absence of renal failure, we studied a group of 84 children in different clinical stages of the disease for a period of five years. We evaluated the direct relationships between lipoproteins, including Lp(a), and/or plasma albumin and proteinuria. RESULTS: Lp(a) levels were significantly higher in the subjects with the active disease compared with patients in remission, and were also significantly different when subjects were ranked by albumin quartiles. Multiple regression analysis revealed that Lp(a) levels were inversely correlated with apo(a) isoform size and plasma albumin levels but not with the proteinuria/creatinine clearance ratio. Among subjects in complete remission, Lp(a) levels were different in patients with albumin levels below or above the fifth percentile. After the improvement of the clinical stage of the disease, the Delta% variation of albumin levels was related to the Delta% of apoB and LDL cholesterol (LDL-C), but not with the Delta% variation of Lp(a), whereas the Delta% variation of LDL-C was, in turn, related to the Delta% of Lp(a) levels. CONCLUSIONS: These results suggest that in the childhood nephrotic syndrome, the increased Lp(a) levels are mainly related to hypoalbuminemia, probably through a mechanism involving apoB overproduction, which leads to an increased number of LDL particles to be converted into Lp(a).     

Lipoprotein(a) stimulates growth of human mesangial cells and induces activation of phospholipase C via pertussis toxin-sensitive G proteins

BACKGROUND: Renal disease is commonly associated with hyperlipidemia and correlates with glomerular accumulation of atherogenic lipoproteins, for example, lipoprotein(a) [Lp(a)], and mesangial hypercellularity. Specific binding of Lp(a) to mesangial cells and induction of c-myc and c-fos expression has been demonstrated. Therefore, in this study, we investigated a possible growth stimulatory effect and mode of action of Lp(a) in human mesangial cells. METHODS: Lp(a) was purified from the regenerate fluid of a dextran sulfate column-based low-density lipoprotein apheresis system. Human mesangial cells were isolated by a sequential sieving technique from patients undergoing tumor nephrectomy. DNA synthesis was measured by [3H]-thymidine incorporation. The intracellular calcium concentration ([Ca2+]i) was determined by Fura 2-fluorescence, and inositol 1,4,5-trisphosphate (1,4,5-IP3) concentration was measured by a radioreceptor assay. RESULTS: The data show that Lp(a) bound to the cells with a Kd of 17.0 micrograms/ml and increased DNA synthesis and cell proliferation. Lp(a) caused a rapid increase in 1,4,5-IP3 and [Ca2+]i via a pertussis toxin-sensitive mechanism. The phospholipase C (PLC) inhibitor U73122 abolished Lp(a)-induced cell proliferation. In contrast, vasopressin-induced increase in 1,4,5-IP3 and [Ca2+]i was pertussis toxin insensitive. CONCLUSION: This study revealed that Lp(a) stimulates growth of human mesangial cells. Lp(a)-induced signaling involves binding to a receptor and stimulation of PLC via Gi proteins. Stimulation of PLC appears to be essential for the growth stimulatory effect of Lp(a). Whether these effects of Lp(a) contribute to the pathophysiology of renal disease needs to be determined.     

Effects of renal replacement therapy on plasma lipoprotein(a) levels

Patients with end-stage renal disease (ESRD) have significantly higher levels of lipoprotein(a) [Lp(a)] when compared to control populations. Elevated levels of Lp(a) may play a role in the high incidence of cardiovascular disease in ESRD. We conducted a prospective study to test the hypothesis that plasma levels of Lp(a) decline rapidly after renal transplantation proportional to the improvement in renal function, but are not affected by hemodialysis. All adults that initiated hemodialysis or received a renal transplant from our institution during a 10-month period were invited to participate in the study. Lp(a) levels were obtained immediately prior to the initiation of renal replacement therapy. In transplant recipients, repeat Lp(a) measures were done at 3 days, 5 days, 1 week, 2 weeks, 3 weeks and 4 weeks post-transplant. In hemodialysis patients, repeat Lp(a) measures were done after 3 months. We used a mixed effects model to analyze the effect of time, race and creatinine on Lp(a) after transplant. Lp(a) levels decreased rapidly after renal transplantation. Mean Lp(a) levels at 2 weeks were 35.3% lower than prior to transplantation. Each reduction of 50% in creatinine was associated with a 10.6% reduction in Lp(a) (p < 0.001). In contrast, there was no significant change in Lp(a) after initiation of hemodialysis. The rapid decrease of Lp(a) levels after renal transplantation provides support for a metabolic role of the kidney in Lp(a) catabolism and suggests that the increase in Lp(a) seen in chronic kidney disease is due to loss of functioning renal tissue.     

An increased serum level of free Apo(a) in renal patients is more striking than that of Lp(a) and is influenced by homocysteine

Lipoprotein(a) [Lp(a)] excess combined with hyperhomocysteinaemia and hyperfibrinogenaemia may contribute to the high incidence of vascular diseases in dialysis patients. This study is aimed at investigating the role of free apolipoprotein(a) [fapo(a)] in renal patients. We have been able to show that, as compared with controls (0.53 mg/l), the median serum concentrations of fapo(a) in patients with nephrotic syndrome (2.58 mg/l) and with peritoneal dialysis (3. 40 mg/l) were strongly elevated (5- to 7-fold), while the fapo(a) levels in patients undergoing haemodialyis (1.02 mg/l) and after renal transplantation (0.90 mg/l) were about doubled. The observed differences in fapo(a) levels indicate that several mechanisms may increase the level of fapo(a), i.e., reduced renal clearance, enhanced hepatic synthesis, or homocysteine releasing apolipoprotein(a) from Lp(a). In the study collective, the median total homocysteine levels were significantly elevated in all patient groups, stronger in patients on haemodialysis (31.4 micromol/l) and peritoneal dialysis (31.2 micromol/l) than in patients with nephrotic syndrome (19.7 micromol/l) and after renal transplantation (19.5 micromol/l). In transplant patients with adequate renal function and without other apolipoprotein(a)-increasing factors, fapo(a) was significantly increased when total homocysteine exceeded 22 micromol/l. In conclusion, our findings let us presume that an increased fapo(a) level in renal patients possibly could be one of the reasons contributing to the high incidence of vascular diseases in these patients, because fapo(a) not covalently linked with Lp(a) is even more easily able to inhibit the fibrinolytic system than the complete Lp(a). These preliminary results have to be confirmed by further investigations.     

Impact of apolipoprotein(a) phenotypes on long-term renal transplant survival

The long-term success of renal transplantation is limited because of chronic rejection (CR), which shows histologic parallels to atherosclerosis. Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis, but its role in CR has not been investigated. Plasma levels of Lp(a) are determined mainly by the inherited isoform (phenotype) of apolipoprotein(a) [apo(a)] and show an inverse correlation with the molecular weight of apo(a). Apo(a) isoforms were identified in frozen sera of 327 patients who received a renal transplant during 1982 to 1992. Long-term graft survival in recipients with high molecular weight (HMW) or low molecular weight (LMW) apo(a) phenotypes were compared retrospectively. Mean (95% confidence interval) transplant survival was 12.8 yr (range, 11.9 to 13.6 yr) in patients with HMW and 11.9 yr (range, 10.8 to 13.1 yr) in patients with LMW apo(a) phenotypes (P = 0.2065). In patients who were 35 yr or younger at the time of transplantation, mean transplant survival was more than 3 yr longer in recipients with HMW apo(a) phenotypes compared with those with LMW apo(a) phenotypes (13.2 yr [range, 12.1 to 14.4 yr] versus 9.9 yr (range, 8.5 to 11.5 yr); P = 0.0156). In a Cox's proportional hazards regression model, the presence of LMW phenotypes-but not gender, immunosuppression, or HLA mismatches-in young patients was associated with a statistically significant risk of CR (P = 0.0434). These retrospective data indicate that young renal transplant recipients with LMW apo(a) phenotypes have a significantly shorter long-term graft survival, regardless of the number of HLA mismatches, gender, or immunosuppressive treatment.     

Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients?--a meta-analysis of randomized controlled trials

OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs) - of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. METHOD: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. RESULTS: The three studies (287 patients and a median trial-duration of 3 months) - all supported by the manufacturer (Hyben-Vital International) - showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13-0.60], P=0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I(2)=0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P=0.0009); corresponding to a NNT of six (95% CI: 4-13) patients. CONCLUSIONS: Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial.     

Perthes' disease: prognosis in children under six years of age

Children presenting with Perthes' disease before their sixth birthday are considered to have a good prognosis. We describe 166 hips in children in this age group. The mean age at onset of the disease was 44 months (22 to 72). Mild forms (Catterall I and II) were treated conservatively and severe forms (Catterall III and IV) either conservatively or operatively. The aim of the former treatment was to restrict weight-bearing. Operative treatment consisted of innominate osteotomy and was indicated by a Conway type-B appearance on the bone scan. All the patients were followed to skeletal maturity with a mean follow-up of 11 years (8 to 15). The end results were evaluated radiologically using the classifications of Stulberg and Mose. A total of 50 hips were Catterall grade-I or grade-II, 65 Catterall grade-III and 51 Catterall grade-IV. All hips with mild disease had a good result at skeletal maturity. Of the hips with severe disease 78 (67.3%) had good (Stulberg I and II), 26 (22.4%) fair (Stulberg III) and 12 (10.3%) poor results (Stulberg IV and V). Of the Catterall grade-III hips 38 were treated conservatively of which 31 (81.6%) had a good result, six (15.8%) a fair and one (2.6%) a poor result. Operative treatment was carried out on 27 Catterall grade-III hips, of which 21 (77.8%) had a good, four (14.8%) a fair and two (7.4%) a poor result. By comparison conservative treatment of 19 Catterall grade-IV hips led to ten (52.7%) good, seven (36.8%) fair and two (10.5%) poor results. Operative treatment was carried out on 32 Catterall grade-IV hips, of which 16 (50.0%) had a good, nine (28.1%) a fair and seven (21.9%) a poor result. We confirm that the prognosis in Perthes' disease is generally good when the age at onset is less than six years. In severe disease there is no significant difference in outcome after conservative or operative treatment (p > 0.05). Catterall grade-III hips had a better outcome according to the Stulberg and Mose criteria than Catterall grade-IV hips, regardless of the method of treatment.     

Dynamic skin cooling with an environmentally compatible alternative cryogen during laser surgery

BACKGROUND AND OBJECTIVES: Cryogen spray cooling with tetrafluoroethane (R134a) has been used to enhance epidermal protection during dermatologic laser surgery. However, R134a has a very high global warming potential (GWP = 1300). Our objective was to evaluate the cooling effectiveness of an alternative cryogen with a much lower GWP, namely liquid carbon dioxide (CO(2), GWP = 1). STUDY DESIGN/MATERIALS AND METHODS: A thin-film thermocouple deposited on an epoxy skin phantom was used to measure surface temperature (T(s)) variations induced by R134a or CO(2) sprays. The temperature distribution in the skin phantom was estimated using T(s) and Duhamel's method. Impact pressure and noise level of both cryogen sprays were measured with a dynamic sensor and sound meter, respectively. Consumption of both cryogens was also evaluated. RESULTS: For R134a sprays, T(s) was kept almost constant after 15 milliseconds. For CO(2) sprays, T(s) decreased continuously during the entire spurt of 50 milliseconds. The minimum T(s) induced by the CO(2) sprays was lower than that induced by R134a when the spurt duration was longer than 35 milliseconds. Numerical simulation shows that CO(2) sprays were able to induce very similar temperature reductions in the skin phantom as compared to R134a sprays when the spurt duration and delay time were selected appropriately. R134a sprays induced an impact pressure of 3.6 kPa, as compared to 43.1 kPa for CO(2) sprays. The maximum noise level for R134a sprays was 109 dBA as compared to 135 dBA for the CO(2) sprays. The R134a consumption for a 50 milliseconds spurt is 67 mg as compared to 225 mg for a CO(2) spurt of the same duration. CONCLUSIONS: CO(2) sprays are expected to have similar skin cooling efficacy as R134a sprays. Although the CO(2) consumption is higher than R134a, its contribution to global warming is still much less than R134a. The effects of varying spurt durations on in vivo human skin and the impact on cutaneous blood flow require further investigation.     

Biomechanical comparison of four methods of repair of the Achilles tendon: a laboratory study with bovine tendons

We tested four types of surgical repair for load to failure and distraction in a bovine model of Achilles tendon repair. A total of 20 fresh bovine Achilles tendons were divided transversely 4 cm proximal to the calcaneal insertion and randomly repaired using the Dresden technique, a Krackow suture, a triple-strand Dresden technique or a modified oblique Dresden technique, all using a Fiberwire suture. Each tendon was loaded to failure. The force applied when a 5 mm gap was formed, peak load to failure, and mechanism of failure were recorded. The resistance to distraction was significantly greater for the triple technique (mean 246.1 N (205 to 309) to initial gapping) than for the Dresden (mean 180 N (152 to 208); p = 0.012) and the Krackow repairs (mean 101 N (78 to 112; p < 0.001). Peak load to failure was significantly greater for the triple-strand repair (mean 675 N (453 to 749)) than for the Dresden (mean 327.8 N (238 to 406); p < 0.001), Krackow (mean 223.6 N (210 to 252); p?相似文献   

Influence of orientation of bi-leaflet valve prostheses on coronary perfusion pressure in humans

Orientation of a bi-leaflet prosthesis (BLP) might influence coronary perfusion. The aim of this study was to investigate the influence of the orientation on coronary perfusion pressure during hyperemia and adrenergic stimulation. During hyperemia perfusion pressure determines coronary blood flow. Fourteen patients with normal coronary angiogram underwent aortic valve replacement (AVR) by a BLP, and seven received a bio-prosthesis. Patients receiving a BLP were randomized to either orientation A (hinge mechanism perpendicular to a line drawn between the coronary ostia) or B (hinge mechanism parallel to the line between the ostia). Six months after surgery all patients underwent cardiac catheterization. Pressures were measured during resting conditions, during maximum hyperemia, and during maximum adrenergic stimulation with a guiding catheter in the aortic arch (P(ao)), simultaneously with a sensor tipped guide wire in the coronary artery (P(cor)) and in the aortic root (P(root)). P(ao)-P(root) described a flow-induced pressure drop in the aortic root (Venturi effect) and the gradient P(root)-P(cor) described coronary ostium abnormalities. Only small non-significant differences in myocardial perfusion pressure were found between different orientations of a bi-leaflet prosthesis or between bi-leaflet prostheses and bio-prostheses in P(ao)-P(root) and P(root)-P(cor).     

The value of synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements

We analysed the serum C-reactive protein level, synovial fluid obtained by joint aspiration and five synovial biopsies from 145 knee replacements prior to revision to assess the value of these parameters in diagnosing late peri-prosthetic infection. Five further synovial biopsies were used for histological analysis. Samples were also obtained during the revision and incubated and analysed in an identical manner for 14 days. A total of 40 total knee replacements were found to be infected (prevalence 27.6%). The aspiration technique had a sensitivity of 72.5% (95% confidence interval (CI) 58.7 to 86.3), a specificity of 95.2% (95% CI 91.2 to 99.2), a positive predictive value of 85.3% (95% CI 73.4 to 100), a negative predictive value of 90.1% (95% CI 84.5 to 95.7) and an accuracy of 89%. The biopsy technique had a sensitivity of 100%, a specificity of 98.1% (95% CI 95.5 to 100), a positive predictive value of 95.2% (95% CI 88.8 to 100), a negative predictive value of 100% and an accuracy of 98.6%. C-reactive protein with a cut-off-point of 13.5 mg/l had a sensitivity of 72.5% (95% CI 58.7 to 86.3), a specificity of 80.9% (95% CI 73.4 to 88.4), a positive predictive value of 59.2% (95% CI 45.4 to 73.0), a negative predictive value of 88.5% (95% 81.0 to 96.0 CI) and an accuracy of 78.1%. We found that biopsy was superior to joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements.     

Idiopathic flexible flatfoot in the adolescent

In summary, factors to consider in treatment are (1) the patient's age; (2) the flexibility of the condition; (3) the severity of deformity; (4) the presence of equinus; (5) abnormal shoe wear; and (6) the symptoms. When a child presents with severe flexible flatfoot one should rule out an underlying neuromuscular disorder and perform a complete biomechanical evaluation to ascertain any rotational or angular conditions of the legs that might influence the treatment. If a child is in group 1 (ages 4 to 7), a Helfet heel seat with a medial plantar wedge is usually adequate treatment. In the group II (ages 8 to 12) adolescent with flexible flatfoot, more control of the calcaneal eversion is needed. This is obtained by using a device constructed from a plaster mold taken while the foot is in neutral position. This UCBL type of device must usually extend to the metatarsal heads and be elevated on the medial and lateral sides. The group III (ages 13 to 17) adolescent usually has the additional problem of a forefoot varus, which must be controlled using a forefoot post. It is also not unusual to have to add additional wedging inside the heel of the shoe to invert the heel.     

Formation of C5a during cardiopulmonary bypass: inhibition by precoating with heparin

A novel enzyme immunoassay based on direct detection of C5a by a monoclonal antibody (C17/5) specific for a neoepitope exposed in C5a/C5adesArg was used to measure in vivo and in vitro C5a formation during cardiopulmonary bypass. In vivo, we observed a significant threefold to fourfold increase in patient plasma C5a/C5adesArg levels from baseline values (5.6; 1.6 to 12.9 ng/mL) (median and range) up to 42 hours postoperatively (17.5; 6.5 to 46.0 ng/mL) when two different uncoated cardiopulmonary bypass circuits were used. Coating of the extracorporeal circuit with end-point-attached heparin completely abolished C5a formation in vitro during circulation of blood through the circuit for 120 minutes. The C5a concentration (median and range) was 3.2 (2.6 to 15.9) ng/mL at the start and 3.1 (2.7 to 15.0) ng/mL at the end of the experiment. In the uncoated setups the corresponding C5a concentrations were 10.1 (6.2 to 17.5) and 19.7 (13.1 to 24.3) ng/mL. Finally, heparin-coated cardiopulmonary bypass circuits were examined in vivo. C5a levels did not increase significantly during the cardiopulmonary bypass period in the heparin-coated group in contrast to the uncoated group, but the postoperative increase in C5a levels was similar in the two groups. We conclude that heparin coating improves biocompatibility by completely abolishing C5a formation in vitro. The discrepancy between the in vitro and the in vivo findings is probably related to the complicated biological turnover of C5a.     

Significance of carbohydrate antigen sialyl-Lewis X, sialyl-Lewis A, and possible unknown ligands to adhesion of human urothelial cancer cells to activated endothelium

OBJECTIVE: To assess the contribution of the carbohydrate antigens, sialyl-Lewis X (sLe(x)) and sialyl-Lewis A (sLe(a)), which are known to be ligands for E-selectin, to the adhesion between human urothelial cancer cells and cytokine-activated human endothelial cells. MATERIALS AND METHODS: We studied the expression of sLe(x) and sLe(a) antigens of three bladder cancer cell lines (JTC 30, JTC 32, and T24) by flow cytometry and the adherence to interleukin 1beta-activated human umbilical vein endothelial cells (HUVEC). RESULTS: JTC 30 and JTC 32 cells expressed both sLe(x) and sLe(a) antigens, and showed adhesion to activated HUVEC, which was completely abolished by anti-E-selectin antibody. T24 cells expressed neither sLe(x) nor sLe(a) antigen, and did not adhere to activated HUVEC. Each of anti-sLe(a) or anti-sLe(x) antibody partially blocked the attachment of JTC 30 cells to activated HUVEC, and combination of these antibodies almost completely blocked the adhesion. The combination of antibodies did not significantly influence the adhesion of JTC 32 cells. CONCLUSION: These results indicate that both sLe(a) and sLe(x) carbohydrate antigens are involved in E-selectin-mediated adhesion of some urothelial cancers, and that there might be unknown ligands for E-selectin on urothelial cancer cells.     

Lipoprotein (a) in patients with aortic aneurysmal disease

OBJECTIVE: Lipoprotein (a) is an independent risk factor for atherosclerosis. Atherosclerotic degeneration is usually found in abdominal aortic aneurysms (AAAs), whereas thoracic aortic aneurysms (TAAs) caused by aortic dissection are not suggested to be linked pathogenetically to atherosclerosis. Lipoprotein (a) was analyzed in patients with AAA and TAA and in healthy individuals in relation to the extent of atherosclerosis. METHODS: Included in the case control study were patients with AAA (n = 75) and TAA with dissection (n = 39) and healthy control subjects (n = 43), for a total of 157 participants. Serum lipoprotein (a) was measured with nephelometry. Lipoprotein (a) levels were compared between age-matched and gender-matched paired samples of the three groups, and an association of lipoprotein (a), aortic aneurysm, and the extent of atherosclerosis was determined in multivariate analysis. RESULTS: Median lipoprotein (a) levels of patients with AAA and TAA and of control subjects were 18.9 mg/dL (interquartile range [IQR], <9.6 to 40.5), less than 9.6 mg/dL (IQR, <9.6 to 16.7), and less than 9.6 mg/dL (IQR, <9.6 to 16.3), respectively. Lipoprotein (a) was positively associated with the extent of atherosclerosis in patients and control subjects (P <.0001). Lipoprotein (a) levels of patients with AAA were significantly higher compared with patients with TAA (P <.0001) and control subjects (P <.0001). Multivariate analysis confirmed an independent association between lipoprotein (a) and AAA (P =.009). No significant differences of lipoprotein (a) were found between patients with TAA and control subjects (P =.3). CONCLUSION: The lipoprotein (a) serum level, an indicator of atherosclerosis, is significantly elevated in patients with abdominal aneurysms independently of cardiovascular risk factors and the extent of atherosclerosis. Patients with TAAs caused by dissection have lipoprotein (a) levels comparable with healthy individuals.     

Variation in patient response associated with different preparations of murine monoclonal antibody therapy

The sera of 37 renal and 12 liver allograft recipients treated with OKT3 (42), Leu2a (7), or both (2) monoclonal antibodies were serially analyzed by an enzyme-linked immunosorbent assay to determine the humoral response (IgG) to mAb. Anti-mAb IgG to the treatment mAb was detected in the serum of 23 (76%) renal and 6 (50%) liver OKT3 recipients, and all 7 Leu2a renal recipients, usually within 14 days of mAb completion, but never during the first week of Rx. Each of the 7 Leu2a recipients developed reactivity not only to Leu2a isotype (IgG1), but also to OKT3 isotype (IgG2a). In contrast, only 1 of the 42 renal and liver allograft recipients treated with OKT3 developed reactivity to the Leu2a isotype. Blocking studies indicated that the specificity of the response to the treatment mAb was directed at the idiotype--and, in some patients, to the constant domain (isotype) of the mAb administered. The antibody response to an alternate isotype (IgG2a) observed in Leu2a (IgG1)-treated patients most likely resulted from irrelevant immunoglobulin (IgG2a) in the Leu2a preparation. This reactivity appeared to be specific for the IgG2a subclass. Clinicians administering mAb therapy should be aware that various mAb preparations may contain immunoglobulin isotypes unrelated to the therapeutic mAb. Crossimmunization to the irrelevant immunoglobulins may occur, precluding subsequent use of other mAbs sharing similar isotype.     

Embryologic development and variations in the anatomy of the ulnocarpal ligamentous complex.

Eighteen fetal hand specimens were reviewed in an effort to clarify variations in reports of the ligamentous anatomy of the ulnar side of the wrist. Sizes ranged from 45 mm crown-rump length (CRL) to 325 mm CRL. Representative coronal sections from the 2779 sections available were reviewed. Significant variations in size of triquetral attachment and thickness and consistency of the ulnocarpal ligamentous complex (UCLC) were observed. Each of the specimens exhibited one of four UCLC variations: (1) 5 of 18 (28%) with an average CRL of 187 mm had a dense, thin UCLC, with a focal triquetral attachment; (2) 7 of 18 (39%) with an average CRL of 209 mm had a focal, dense attachment of a thick UCLC to the triquetrum; (3) 5 of 18 (28%) with an average CRL of 220 mm exhibited a thick, dense UCLC with a broad attachment to the triquetrum; and (4) 1 of 18 (5%) with a CRL of 166 mm was unique, with a loose, areolar UCLC broadly attached to the triquetrum.     

The mechanics of corporal veno-occlusion in penile erection: a theory on the effect of stretch-associated luminal constrictability on outflow resistance.

In order to further our understanding of the physiology of corporal veno-occlusion, we developed a theory of a possible contribution to corporal venous outflow resistance which occurs as the result of venule stretching with resultant luminal narrowing when penile volume increases during the erection process. We stretched non-biological tubes and rabbit abdominal vena cava segments, performed flow-based and volume-based experiments to calculate the magnitude of N, the newly defined 'stretch-associated luminal constrictability' factor. We solved for (R(s)/R(u)), the ratio of the venule fluid resistance in the stretched state (R(s)) to the unstretched state (R(u)), to quantify the projected increases in fluid resistance as well as Q.R(u) where Q is the subtunical venule flow rate.For a given tube, N was found to be essentially constant for different amounts of stretch. A theory was formulated which predicted R(s) and Q as a function of N, DeltaP (intracavernosal pressure increase); V(E)/V(F) (tunical distensibility); X (cavernosal expandability) and R(u). Based on the magnitude of N=2, this theory predicts that patients with the highest values of both V(E)/V(F) and X would have maximal R(s) values, approaching infinity (complete occlusion) at a low DeltaP near 5 mmHg. In contrast, patients with low values of both V(E)/V(F) (eg Peyronie's disease) and X (eg corporal fibrosis), would be predicted to have minimal R(s) values. For example, a hypothetical patient with the lowest values of V(E)/V(F) and X would yield R(s) values only approaching 7.9 times that of unstretched values at a DeltaP increase of 90 mmHg.We concluded to that stretch-associated venule resistance may occur as a result of decreased sub-tunical venule diameter and increased sub-tunical venule length. In individual patients, stretch-associated venule resistance may either dominate or be a minor component of the overall mechanism of corporal veno-occlusion.