In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients

Lipoprotein(a) (Lp(a)) consists of a low-density lipoprotein-like particle and a covalently linked highly glycosylated protein, called apolipoprotein(a) (apo(a)). Lp(a) derives from the liver but its catabolism is still poorly understood. Plasma concentrations of this highly atherogenic lipoprotein are elevated in hemodialysis (HD) patients, suggesting the kidney to be involved in Lp(a) catabolism. We therefore compared the in vivo turnover rates of both protein components from Lp(a) (i.e. apo(a) and apoB) determined by stable-isotope technology in seven HD patients with those of nine healthy controls. The fractional catabolic rate (FCR) of Lp(a)-apo(a) was significantly lower in HD patients compared with controls (0.164+/-0.114 vs 0.246+/-0.067 days(-1), P=0.042). The same was true for the FCR of Lp(a)-apoB (0.129+/-0.097 vs 0.299+/-0.142 days(-1), P=0.005). This resulted in a much longer residence time of 8.9 days for Lp(a)-apo(a) and 12.9 days for Lp(a)-apoB in HD patients compared with controls (4.4 and 3.9 days, respectively). The production rates of apo(a) and apoB from Lp(a) did not differ significantly between patients and controls and were even lower for patients when compared with controls with similar Lp(a) plasma concentrations. This in vivo turnover study is a further crucial step in understanding the mechanism of Lp(a) catabolism: the loss of renal function in HD patients causes elevated Lp(a) plasma levels because of decreased clearance but not increased production of Lp(a). The prolonged retention time of Lp(a) in HD patients might importantly contribute to the high risk of atherosclerosis in these patients.     

Relationship of non-LDL-bound apo(a), urinary apo(a) fragments and plasma Lp(a) in patients with impaired renal function.

BACKGROUND: Plasma lipoprotein (a) [Lp(a)] has been shown to be a risk factor for atherosclerosis in numerous studies. However, the catabolism of this lipoprotein is not very clear. We and others have shown that Lp(a) is excreted into urine in the form of fragments. Lp(a) has also been shown to exist in a low-density non-lipoprotein (LDL)-bound form. Since Lp(a) is increased in all forms of kidney disease with reduced excretory kidney function and decreased excretion of apo(a) fragments could be partially responsible for this increase, we investigated the relationship of non-LDL-bound apo(a), urinary apo(a) fragments and plasma Lp(a) in patients with impaired renal function. METHODS: Plasma Lp(a), non-LDL-bound apo(a) and urinary apo(a) fragments were measured in 55 kidney disease patients (28 males and 27 females) and matched controls. RESULTS: Plasma Lp(a) and non-LDL-bound apo(a) were increased in patients, whereas urinary apo(a) was decreased, especially in patients with a creatinine clearance < 70 ml/min. There was a significant correlation between plasma Lp(a) and non-LDL-bound apo(a) in patients and controls. CONCLUSION: We conclude that decreased urinary apo(a) excretion could be one possible mechanism of increased plasma Lp(a) and non-LDL-bound apo(a) in patients with decreased kidney function.     

Peripheral arteriovenous anastomosis: an alternative technique in a free flap transfer.

Prevention of thrombosis in the inflow and outflow vessels of a free flap is a problem of current interest. The method of creating a peripheral arteriovenous anastomosis within a free flap was validated in an experimental study and substantiated in a clinical case. No thrombotic complications were observed in 16 transfers of saphenous fasciocutaneous flaps in a dog model, as well as in an elderly patient with free radial forearm flap transfer to an irradiated foot. Scanning electron microscopy of the venous anastomosis proximal to the arteriovenous fistula revealed the difference of pathologic changes as early as 4 hr following surgery. It is the conclusion of the authors, that performing a distal arteriovenous fistula in a free flap, is an effective procedure for prevention of early occlusion in a proximally anastomosed artery and vein.     

The effect of the syndesmotic screw on the extension capacity of the ankle joint

Summary To investigate whether, when inserting a syndesmotic screw, the foot position effects the range of motion in dorsal extension, 16 osteoligamentous lower-leg preparations were studied. The specimens were placed in a test frame where a constant dorsal extension force could be applied to the foot. The dorsal extension capacity was recorded with a syndesmotic screw inserted by a standardized technique in various plantar flexion positions. The dorsal extension capacity decreased by an average of 0.1° for every degree of increase in plantar flexion when the screw was being inserted. There was a correlation between a large decrease in range of motion and a limited dorsal extension capacity to start with. No correlation could be found between a large decrease in range of motion and a large difference in width between the anterior and posterior edges of the talar trochlea. The results suggest that the foot should be in maximal dorsal extension when a syndesmotic screw is inserted in order to decrease the risk of stiffness.     

Pneumopathie sévère à Adénovirus type 7 chez un adulte immunocompétent

We report a case of severe Adenovirus type 7 pleuropneumonia in an immunocompetent adult. The treatment required a mechanical ventilation with tracheostomy. The sequelae was a restrictive respiratory insufficiency. Adenovirus is a common cause of pneumonia in children, in military recruits or in immunocompromised adults. However, it is an infrequent cause of such a severe complication in a healthy adult.     

Zero‐order asymptotic solution of a class of singularly perturbed linear‐quadratic problems with weak controls in a critical case

We consider a linear‐quadratic optimal control problem where the second power of a small parameter stands in front of the derivative and a control in a state equation and in front of a quadratic form with respect to control in a performance index; moreover, in the state equation, the nonhomogeneity has the first order of the power of a small parameter, and a matrix in front of the state variable is singular if the small parameter is equal to zero. Using immediate substituting a postulated asymptotic expansion of a solution, containing a regular series and four boundary layer functions series, into the problem condition, we obtain problems for finding asymptotic terms of the zero order for the optimal control and the first order for the optimal trajectory. An illustrative example is given.     

The effect of the halovest and body position on pulmonary function in quadriplegia

Pulmonary function (vital capacity) was measured in ten quadriplegics and ten normal subjects in the following situations: supine, sitting, supine with a halovest, and sitting with a halovest. When changing from the supine to sitting positions, vital capacity decreased in the quadriplegics and increased in normal subjects. The halovest significantly reduced the vital capacity in normal subjects, but had much less of a detrimental effect in quadriplegics. As a result of this prospective, controlled study, we conclude the following: (a) the compromised state of pulmonary function in quadriplegics is not a contraindication for the use of a halovest, (b) the halovest causes a significant (p less than 0.01) restriction in vital capacity in able bodied subjects, and (c) when tenuous pulmonary function exists in a quadriplegic, pulmonary mechanics are better in the supine position.     

Congenital disseminated malignant rhabdoid tumor and cerebellar tumor mimicking medulloblastoma in monozygotic twins: pathologic and molecular diagnosis.

Malignant rhabdoid tumors are highly aggressive childhood tumors. Recently, all of the malignant rhabdoid tumors, whatever their location, have been related to the inactivation of the hSNF5/INI1 gene. A subset of cerebral tumors, associated with malignant rhabdoid tumors or isolated ones arising in siblings, showed similar molecular alterations. We report for the first time in monozygotic twins a congenital disseminated malignant rhabdoid tumor in one twin and a cerebellar tumor mimicking a medulloblastoma in the other. Molecular analysis revealed similar alterations for both tumors: a deletion of exon 7 of the hSNF5/INI1 gene in one allele, and a point mutation in the same exon in the other, suggesting a common genetic pathway. Analysis of constitutional DNA revealed a germline mutation. These findings are in favor of a common etiology for rhabdoid tumor and a subset of brain tumors developing in infancy.     

Lipoprotein(a)-associated atherothrombotic risk in hemodialysis patients

BACKGROUND: Hemodialysis patients show a considerably higher risk of atherothrombotic disease than the general population. We investigated both lipoprotein(a) [Lp(a)] plasma levels and apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of atherothrombotic events in hemodialysis patients compared with subjects showing a normal kidney function. Methods: Lp(a) levels and apo(a) isoforms were determined in 118 hemodialysis patients, including 59 with prior atherothrombotic events, and in 182 subjects with normal creatinine clearance, including 82 who experienced a prior atherothrombotic event. Results: Lp(a) levels in hemodialysis patients (median; 20 mg/dl) were higher (p < 0.01) than in age- and sex-matched subjects with normal renal function without a history of atherothrombosis (11.3 mg/dl). Among hemodialysis patients, median Lp(a) levels were higher in subjects with than in those without prior atherothrombosis (34 vs. 15 mg/dl, p < 0.05). In hemodialysis patients and in subjects without nephropathy, the percentage of low-molecular-weight apo(a) phenotypes were significantly higher in patients with than in those without a history of prior atherothrombotic events (56.9% vs. 33.9%, p < 0.05; 62.2% vs. 25%, p < 0.00001,respectively). Stepwise regression analysis indicated that the presence of at least one apo(a) isoform of low molecular weight was an independent predictor of atherothrombosis in hemodialysis patients (p < 0.05). Conclusions: Elevated Lp(a) plasma levels appear to be associated with atherothrombosis, independent of their origin due to genetic factors or related to the impaired kidney function. Low-molecular-weight apo(a) isoforms are reliable genetic markers of atherothrombosis both in patients with impaired kidney function and in subjects without nephropathy.     

Total laparoscopic aortic surgery versus minimal access techniques: review of more than 600 patients

In the following paper we describe our experience with a large number of patients in which either a laparoscopic assisted procedure or a total laparoscopic operation was performed. From 1996 until 2005 a total number of 638 aortic patients were operated on using a total laparoscopic or a laparoscopic assisted approach. A total laparoscopic operation was accomplished in 236 cases. A laparoscopic assisted aortic operation was performed in 402 patients. In aneurysm patients a tube graft was more frequently implanted. Thirty-day mortality was significantly higher in patients with a total laparoscopic abdominal aortic aneurysm repair (3.0%) compared to a laparoscopic assisted procedure (1.8%). There was no significant difference in mortality in patients with occlusive disease and a total laparoscopic aortofemoral bypass versus a laparoscopically assisted operation. The same tendency could be observed when analyzing the incidence of major perioperative complications. Again we found no significant difference in patients with occlusive disease yet more severe complications directly related to the operation in patients with a total laparoscopic aneurysm repair. There was a significantly increased complication rate in total laparoscopic aortoiliac repair with a bifurcated prosthesis compared to a tube graft repair: a tendency we could not observe in aneurysm patients with a laparoscopic assisted operation. Our data also show that there is a lot of room for technical improvements such as stapling devices or special grafts to reduce total operating times as well as the period of aortic crossclamping. The routine use of a minilaparotomy can hardly be a solution considering the technical drawbacks such as impaired vision and long term complications like ventral hernias. Compared to open surgery the midterm results of laparoscopic aortic procedures are promising. The time has come to prove that good results can be obtained in more than a few specialized centers.     

Lipoprotein(a) in the nephrotic syndrome: molecular analysis of lipoprotein(a) and apolipoprotein(a) fragments in plasma and urine

Plasma levels of lipoprotein(a) (Lp(a)), an atherogenic particle, are elevated in kidney disease, which suggests a role of this organ in the metabolism of Lp(a). Additional evidence for a role of the kidney in the clearance of Lp(a) is provided by the fact that circulating N-terminal fragments of apolipoprotein(a) (apo(a)) are processed and eliminated by the renal route. To further understand the mechanism underlying such renal excretion, the levels of apo(a) fragments in plasma and urine relative to plasma Lp(a) levels were determined in patients with nephrotic syndrome (n = 15). In plasma, the absolute (24.7 +/- 20.4 versus 2.16 +/- 2.99 microg/ml, P < 0.0001) as well as the relative amounts of apo(a) fragments (4.6 +/-3.4% versus 2.1 +/- 3.3% of total Lp(a), P < 0.0001) were significantly elevated in nephrotic patients compared with a control, normolipidemic population. In addition, urinary apo(a) excretion in patients with nephrotic syndrome was markedly elevated compared with that in control subjects (578 +/- 622 versus 27.7 +/- 44 ng/ml per mg creatinine, P < 0.001). However, the fractional catabolic rates of apo(a) fragments were similar in both groups (0.68 +/- 0.67% and 0.62 +/- 0.47% in nephrotic and control subjects, respectively), suggesting that increased plasma concentrations of apo(a) fragments in nephrotic subjects are more dependent on the rate of synthesis rather than on the catabolic rate. Molecular analysis of apo(a) immunoreactive material in urine revealed that the patterns of apo(a) fragments in nephrotic patients were distinct from those of control subjects. Full-length apo(a), large N-terminal apo(a) fragments similar in size to those present in plasma, as well as C-terminal fragments of apo(a) were detected in urine from nephrotic patients but not in urine from controls. All of these apo(a) forms were in addition to smaller N-terminal apo(a) fragments present in normal urine. This study also demonstrated the presence of Lp(a) in urine from nephrotic patients by ultracentrifugal fractionation. These data suggest that in nephrotic syndrome, Lp(a) and large fragments of apo(a) are passively filtered by the kidney through the glomerulus, whereas smaller apo(a) fragments are secreted into the urine.     

Negative fluid balance in patients with abdominal compartment syndrome--case reports

Abdominal compartment syndrome (ACS) is defined as a sustained increase of intra-abdominal pressure (IAP) above 20 mmHg followed by the development of organ dysfunction. Treatment of ACS is still a question to be discussed and surgical decompression is usually preferred. According to recent data, massive crystalloid resuscitation of shock plays a key role in the development of secondary ACS in trauma patients. As mentioned previously, a high volume of infused crystalloids and a positive fluid balance were associated with ACS development in trauma patients as well as in septic patients. Moreover, we observed that a treatment strategy based on the achievement of a negative fluid balance resulted in a dramatic decrease in IAP and an improvement in haemodynamics and ventilation. This approach has been indicated as an interesting option for non-surgical treatment, with a caution that such intervention may exacerbate gut hypoperfusion. In this report we present two patients with secondary ACS development following abdominal surgery in which the achievement of a negative fluid balance showed a similar effect. Moreover, the fluid removal procedure also seemed to be associated with an improvement in splanchnic perfusion, as measured by gastric tonometry.     

Vena cava stenting and portorenal shunt in Budd-Chiari syndrome: combination of the 'modern' and the 'classical'.

We have treated a 33-year-old Budd-Chiari patient (due to antiphospholipid syndrome) with a history of myocardial infarction by placing a vascular stent in the inferior vena cava and performing a portorenal shunt with three objectives: (1) to perform a shunt operation on a Budd-Chiari patient with good hepatic functional reserve, (2) to avoid a thoracotomy and manipulation of the heart in a patient with a cardiac thrombus and a history of myocardial infarction and (3) to avoid a synthetic graft in a patient with antiphospholipid syndrome. Vena cava stenting and portorenal shunt make a useful combination which should be included in the armamentarium of the hepatobiliary surgeon.     

Electronic data collection by trainee anaesthetists using palm top computers

The Royal College of Anaesthetist requires that trainees wishing to specialise in Anaesthesia register with the College and keep a logbook documenting their experience and training in clinical anaesthesia. There are a number of advantages if such logbooks are kept in an electronic format. For the first time in the United Kingdom, we have evaluated the usefulness in a district general hospital of introducing a computerized system of record keeping based on a portable palm top computer. This has enabled the careful analysis of the individual work load of each trainee in the department by means of a specific program designed to generate a comprehensive report after the information from each individual has been downloaded on to a standard desk top computer. We have found a number of interesting and unexpected results and have highlighted ways in which the system may be improved.     

Failure of autoregulation after closed head injury: an experimental model

Cats were subjected to a 3.5-atm fluid percussion impact administered to the cerebral cortex. Near-infrared spectrophotometry (NIRS) was used to measure the quantity of oxyhemoglobin and total hemoglobin in the illuminated tissue as well as the cytochrome a, a3 redox state. Corroborative data were obtained by freezing brains with liquid nitrogen and measuring cortical concentrations of ATP, creatine phosphate (CP), and lactate. Immediately postimpact there was a rise in mean arterial pressure with a 38% increase of highly oxygenated blood and a shift toward oxidation in the cytochrome a, a3 redox state. By 4 hours postimpact, cytochrome a, a3 was becoming progressively reduced despite the persistence of hyperemia. This was associated with a significant (p less than 0.01) decrease in ATP and CP concentration. Additional studies in which a 0.5-sec, 100-v electrical seizure was induced before and after fluid percussion demonstrated significant differences in seizure response, indicating a failure of autoregulation.     

Magnetic resonance imaging in planning limb-salvage surgery for primary malignant tumors of bone

In defining the linear extent of a malignant tumor in a long bone, radiographs, computerized tomography, and scintigraphy are routinely employed, especially when non-ablative surgery is being considered. The drawbacks of these modalities in defining the true intracompartmental extent of disease within a bone can largely be overcome with the use of magnetic resonance imaging. We did a prospective analysis of magnetic resonance imaging in sixteen consecutive patients with a primary malignant tumor of a long bone, and it showed that this modality has clinical promise of being more precise than the other modalities in defining the true proximal and distal extent of a tumor in a long bone. Coronal images permit easier planning of surgical techniques for salvage of a limb using an allograft than do a multiplicity of transverse images.     

Suprapubic prostatectomy for benign prostatic hyperplasia in rural Asia: 200 consecutive cases

Objectives. To assess the safety and efficacy of a suprapubic prostatectomy technique performed in a rural hospital in Asia.Methods. A retrospective study of 200 consecutive suprapubic transvesical prostatectomies with a removable bladder neck partition suture for benign prostatic hyperplasia from 1995 to 1998 in a rural mission hospital in northern Pakistan was performed.Results. Despite preoperative comorbidities in 28% of patients, the postoperative morbidity (14%) and mortality (1%) was low. The partition suture is credited with a very low transfusion rate (1%) and a lower intensity of nursing care in the postoperative period. Patient satisfaction was high with regard to both relief of symptoms and cost.Conclusions. This study demonstrated that suprapubic prostatectomy with a routine bladder neck partition suture for benign prostatic hyperplasia can be carried out with a high degree of safety and efficacy in a rural setting with limited facilities in a developing country.     

Apolipoprotein(A) expression in intracranial aneurysms

OBJECTIVE: Elevated serum levels of lipoprotein(a), a risk factor for atherosclerosis (AS), are also associated with the presence of asymptomatic intracranial aneurysms. AS is present in some aneurysms, but its contribution to aneurysm formation and growth is unclear. Apolipoprotein(a) [apo(a)], the active moiety of lipoprotein(a), is present in atherosclerotic circle of Willis vessels but not in normal circle of Willis vessels. We wished to determine whether apo(a) is present in intracranial aneurysms independently of AS. METHODS: With a purified anti-apo(a) monoclonal antibody, aneurysms (n = 25) and feeding vessels (n = 23) were examined for apo(a) expression by immunohistochemical analysis. Circle of Willis arteries with and without AS (n = 19), cavernous angiomas (n = 5), and arteriovenous malformations (n = 6) acted as control samples. RESULTS: AS was present in 32% of aneurysms, and all of those aneurysms demonstrated mural immunopositivity for apo(a). However, aneurysms devoid of AS also demonstrated apo(a) immunopositivity. Apo(a) was demonstrated in 86% of available feeding vessels. Apo(a) deposition was not observed in cavernous angiomas but was present in arteriovenous malformations. Eleven Circle of Willis arteries (57.9%) were devoid of AS and demonstrated no apo(a) immunostaining, whereas the eight (42.1%) with AS were immunopositive for apo(a). CONCLUSION: Apo(a) expression in intracranial aneurysms may occur independently of AS. Apo(a) in feeding vessels suggests a possible role for apo(a) in early events leading to aneurysm formation. Multilayered transmural apo(a) deposition in established aneurysms suggests apo(a) involvement in aneurysm growth, possibly via cycles of injury and repair. The absence of apo(a) in cavernous angiomas suggests that such injury might be pressure-mediated.     

Transient simultaneous sciatic and femoral nerve palsy secondary to iliacus and gluteal hematomas following heparinization for pulmonary embolus in a patient with posterior hip dislocation

Sciatic nerve palsy as a result of a posterior hip dislocation has been reported in the literature. Femoral nerve palsy as a result of a iliacus hematoma has also been documented. However, a simultaneous sciatic and femoral nerve palsy occurring after heparinization for a pulmonary embolus in a patient with a posterior hip dislocation has not been reported. This combined nerve palsy was found in a 64-year-old white woman who had been involved in a motor vehicle accident and sustained a posterior hip dislocation. This patient subsequently had a pulmonary embolism, was heparinized, and then developed a large iliacus and gluteal hematoma, resulting in a simultaneous sciatic and femoral nerve palsy. Without treatment, the patient regained motor and sensory of the sciatic nerve in a few days, and a gradual improvement of function of her femoral nerve was evident over several months.     

The effect of the syndesmotic screw on the extension capacity of the ankle joint

To investigate whether, when inserting a syndesmotic screw, the foot position effects the range of motion in dorsal extention, 16 osteoligamentous lower-leg preparations were studied. The specimens were placed in a test frame where a constant dorsal extention force could be applied to the foot. The dorsal extention capacity was recorded with a syndesmotic screw inserted by a standardized technique in various plantar flexion positions. The dorsal extension capacity decreased by an average of 0.1 degree for every degree of increase in plantar flexion when the screw was being inserted. There was a correlation between a large decrease in range of motion and a limited dorsal extension capacity to start with. No correlation could be found between a large decrease in range of motion and a large difference in width between the anterior and posterior edges of the talar trochlea. The results suggest that the foot should be in maximal dorsal extension when a syndesmotic screw is inserted in order to decrease the risk of stiffness.