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.     

Communication between functional and denervated muscles using radiofrequency.

OBJECTIVE: This article focuses on establishing communication between a functional muscle and a denervated muscle using a radiofrequency communications link. The ultimate objective of the project is to restore the eye blink in patients with facial nerve paralysis. STUDY DESIGN AND SETTING: Two sets of experiments were conducted using the gastrocnemius leg muscles of Sprague-Dawley rats. In the initial tests, varying magnitudes of voltages ranging from 0.85 to 2.5 V were applied directly to a denervated muscle to determine the voltage required to produce visible contraction. The second set of experiments was then conducted to determine the voltage output from an in vivo muscle contraction that could be sensed and used to coordinate a signal for actuation of a muscle in a separate limb. After designing the appropriate external communication circuitry, a third experiment was performed to verify that a signal between a functional and a denervated muscle can be generated and used as a stimulus. RESULTS: Voltages below 2 V at a 10-millisecond pulse width elicited a gentle, controlled contraction of the denervated muscle in vivo. It was also observed that with longer pulse widths, higher stimulation voltages were required to produce sufficient contractions. CONCLUSION: It is possible to detect contraction of a muscle, use this to generate a signal to an external base station, and subsequently cause a separate, denervated muscle to contract in response to the signal. SIGNIFICANCE: This demonstration in vivo of a signaling system for pacing of electrical stimulation of 1 muscle to spontaneous contraction of another, separate muscle, using radiofrequency communication without direct connection, may be used in numerous ways to overcome nerve damage.     

Applied cardiovascular physiology

The cardiovascular responses to exercise, haemorrhage, Valsalva manoeuvre, postural changes and exposure to microgravity are complex patterns made up of a number of common physiological ‘building blocks’. The main cardiovascular response to isotonic exercise is an increase in cardiac output to elevate oxygen delivery to exercising muscle. This is largely mediated via an increase in heart rate and facilitated by an increase in venous return. By contrast, in haemorrhage a reduced venous return leads to a reduction in cardiac output, a fall in arterial pulse pressure and unloading of the arterial baroreceptors. The baroreceptor reflex response is designed to maintain arterial blood pressure by increasing peripheral vascular resistance and limiting the fall in cardiac output via a positive inotropic effect and tachycardia. But, because venous return falls in haemorrhage, the tachycardia is relatively ineffective in sustaining cardiac output (in contrast to the situation in exercise). As the haemorrhage becomes severe, a second reflex, causing a profound vagally mediated bradycardia and hypotension, becomes apparent. This ‘depressor’ reflex is blocked by the response to musculoskeletal injury, hence the biphasic response to ‘simple’ haemorrhage is often not seen in trauma patients. Changing posture and performing the Valsalva manoeuvre also reduce venous return and lead to a reflex tachycardia, an increase in peripheral resistance, and maintenance of arterial blood pressure by mechanisms similar to those seen in the early response to blood loss. By recording the responses to a Valsalva manoeuvre or postural changes, aspects of the reflex control of the cardiovascular system can be assessed and quantified. Finally, movement from supine to standing and exposure to microgravity lead to a movement of fluid from the vascular space to the interstitium because of a disturbance in Starling’s forces, leading to hypovolaemia. By contrast, after haemorrhage an alteration in Starling’s forces result in the movement of fluid from the interstitium to the vasculature to aid an early restoration of intravascular volume.     

Delayed diagnosis of injuries to the diaphragm after penetrating wounds

During a 9-year period, 16 patients with a delay in diagnosis of an injury to the diaphragm after a penetrating wound were treated. The left hemidiaphragm was involved in 15 of 16 patients, and the delay in diagnosis from the time of arrival in the emergency center immediately after injury ranged from 16 hours to 14 years. In the patients in the Acute Group (delay of hours to days), three patients had diaphragmatic defects missed at the time of laparotomy, three patients had chest X-rays not immediately suggestive of diaphragmatic defects, two patients had false-negative lavages, and one patient treated elsewhere did not have a chest X-ray in the emergency room. In the patients in the Chronic Group (hernias presenting months to years after injury), four of seven patients had misreading of a recent chest X-ray or failure to have a chest X-ray performed during numerous return visits to the emergency center. Despite a variety of diagnostic maneuvers, these defects and hernias continue to be diagnosed after a delay. Careful review of early and late followup chest X-rays appears to be the easiest mechanism to avoid significant delays in diagnosis.     

Simultaneous bilateral pneumothorax. Case report

A case report of a 44 year-old white man admitted to the surgical unit for a bilateral simultaneous pneumothorax is presented. The pneumothorax occurred on day one after a surgical operation for discal hernia; in the past the patient already presented a right spontaneous pneumothorax at 32 years of age and a left pneumothorax at 37 years of age, both treated with a pleural drainage. A thoracic drain was bilaterally positioned with a good result only in the right side. The persistence of the left pneumothorax induced the authors to perform a postero-lateral thoracotomy bullae excision and pleurectomy with a good postoperative course. After a few months a new right pneumothorax occurred and the patient was treated with a right postero-lateral thoracotomy, bullae resection and pleurectomy. On the basis of the case reported, the authors consider the different opportunities in the treatment of spontaneous pneumothorax in relation to the present knowledges and technologies. Surgical procedure is to be preferred in case of persistence of pneumothorax despite a pleural drain and in case of pneumothorax in high risk subjects. Even if thoracoscopy seems to give better results regarding postoperative pain, it is not always possible with such a method to perform a careful pleurectomy neither to obtain it in all cases (above all in secondary pneumothorax). Every case must then be carefully studied to choose the best treatment at present available.     

Applied cardiovascular physiology

The cardiovascular responses to exercise, haemorrhage, a Valsalva manoeuvre, postural changes and exposure to microgravity are complex patterns made up of a number of common physiological ‘building blocks’. The main cardiovascular response to isotonic exercise is an increase in cardiac output to elevate oxygen delivery to exercising muscle. This is largely mediated via an increase in heart rate and facilitated by an increase in venous return. By contrast, in haemorrhage a reduced venous return leads to a reduction in cardiac output, a fall in arterial pulse pressure and unloading of the arterial baroreceptors. The baroreceptor reflex response is designed to maintain arterial blood pressure by increasing peripheral vascular resistance and limiting the fall in cardiac output via a positive inotropic effect and tachycardia. But, because venous return falls in haemorrhage, the tachycardia is relatively ineffective in sustaining cardiac output (in contrast to the situation in exercise). As the haemorrhage becomes severe, a second reflex, causing a profound vagally mediated bradycardia and hypotension, becomes apparent. This ‘depressor’ reflex is blocked by the response to musculoskeletal injury, hence the biphasic response to ‘simple’ haemorrhage is often not seen in trauma patients. Changing posture and performing the Valsalva manoeuvre also reduce venous return and lead to a reflex tachycardia, an increase in peripheral resistance, and maintenance of arterial blood pressure by mechanisms similar to those seen in the early response to blood loss. By recording the responses to a Valsalva manoeuvre or postural changes, aspects of the reflex control of the cardiovascular system can be assessed and quantified. Finally, movement from supine to standing and exposure to microgravity lead to a movement of fluid from the vascular space to the interstitium because of a disturbance in Starling’s forces, leading to hypovolaemia. By contrast, after haemorrhage an alteration in Starling’s forces results in the movement of fluid from the interstitium to the vasculature to aid an early restoration of intravascular volume.     

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.     

Changes in emergency surgery between 1973 and 1982: audit of the workload of one surgical team

The emergency surgical workload of a consultant in general surgery has been studied by comparing two prospectively collected audits of 6-month periods 9 years apart. There have been a number of changes in the pattern and intensity of general surgical admissions (excluding trauma) with a decline in the total number per day from 14.1 to 12.4 and a reduction in the number of days on call for general surgery from 30 to 14 over the 6-month period. There was a similar fall in days on call for trauma from 60 to 23 days and a decline in total emergency surgical operations from 6.6 to 5.2 operations per night on call. These changes have mainly been produced by an increase in the number of consultants in the hospital from five to eight and specialisation with the establishment of an area urology unit. The results of this study suggest that as consultant numbers increase in a particular area there will be diminished exposure of surgical trainees to emergency cases both in quantity and in quality, and this loss of experience will prove deleterious to the trainee surgeon.     

A note on the early history of renal transplantation: Emerich (Imre) Ullmann

In January 1902 at the Vienna Medical Society Meeting, the surgeon Emerich Ullmann reported the first case of renal autotransplantation performed in the neck of a dog. In the same year, he presented the first xenotransplantation of the kidney (a goat with a dog's kidney). These publications immediately had a great impact on the medical word. After his failed attempt to transplant a pig's kidney into a young uraemic woman he stopped his research in this field in order to devote himself to other lines of surgical research. However, his idea survived him, because, nowadays, nearly 100 years later, pigs appear to be the most suitable donors for human renal xenotransplantation. Ullmann was born in Pécs, Hungary, on February 23, 1861. After a distinguished undergraduate career in 1878 his father (being also a medical doctor) sent him to study medicine at the world-famous Vienna Medical School. He graduated in 1884 and was immediately invited to the Surgical Department where Billroth worked. Next year, because of his interest in bacteriology he visited Pasteur in Paris and successfully volunteered to serve as a healthy subject to prove the effectiveness of Pasteur's antisera against rabies. Although Ullmann did not succeed in doing a human transplantation he gave birth to the era of the organ transplantation, stimulated vascular surgery and the development of transplantation immunology.     

Clinical fracture of the carpal scaphoid—An illusionary diagnosis

The management of patients with clinical evidence of a fracture of the carpal scaphoid bone but without radiological evidence of a fracture is based on dogma emphasizing the need to immobilize the wrist in all cases. Because of the apparently high proportion of patients who spend up to six weeks in a plaster cast and in whom no fracture is ever demonstrated radiologically, a study was undertaken to determine the fate of those wrist injuries diagnosed as clinical fractures of the scaphoid. All patients who presented with clinical or radiological evidence of fractures of the scaphoid over a one year period were reviewed. Of the 108 patients in whom the diagnosis of clinical fracture of the scaphoid was made at the time of presentation none was proved radiologically to have a fracture of the scaphoid subsequently after a period of mobilization. These patients spent an average time of 21.9 days in a plaster cast which represents a significant loss of productivity to the community and inconvenience to the patient.     

Repair of Dural Defects in Awkward Areas-Technical Note

Summary  Dural tears located at the base of the skull are difficult to repair due to the difficulties in the appropriate access and the fragility of the dura in such areas.  In our experience the biggest problem when attempting to perform a dural repair in a deep narrow field is not to place the stitches, but rather to set the knots. A newly designed, easy-to-learn technique has been developed for dural closure in these situations. We present here a new technique for dural suturing of special interest when the space available is limited.  In our hands it is possible to obtain a watertight dural closure in most microsurgical operations performed through a small hole and/or into a narrow, deep surgical field. These techniques can also be applied during a secondary procedure following development of a postoperative CSF leak. While simple and easy to learn, these techniques require practice in the laboratory setting before clinical application.     

The coexistence of lobular carcinoma in a fibroadenoma with a malignant phyllodes tumor in the opposite breast: Report of a case

It is very unusual for a carcinoma of the breast to coexist with a phyllodes tumor, or for a carcinoma to arise within a fibroadenoma. We present herein an extremely rare case of lobular carcinoma in situ arising in a fibroadenoma, associated with a malignant phyllodes tumor in the opposite breast. A 49-year-old woman was admitted to our hospital with a large mass in the right breast and a small mass in the left breast. Microscopic examination of biopsy materials revealed a malignant phyllodes tumor in the right breast and a fibroadenoma in the left breast, for which a right standard radical mastectomy and left lumpectomy were performed. Microscopic findings of the material excised from the left breast showed the presence of multiple lobular carcinoma in situ within the tumor mass of the fibroadenoma. However, histological examination did not detect any metastasis to the bilateral axillary lymph nodes. To our knowledge this is the only such case ever to be reported in Japan.     

Breast cancer control: signs of progress, but more work required

Breast cancer represents 10% of the global cancer burden and there is no population, or population sub-group, which has yet been identified to be at a truly low risk of developing the disease. Mortality rates have been steadily growing for nearly a century in many countries and it is only during the past decade that there have been signs of a sustainable decrease in mortality rates in a number of western-lifestyle countries. This represents considerable progress in breast cancer control and, although different factors contribute to different degrees in different countries, is mainly due to increased breast awareness, earlier detection and the delivery of the most appropriate therapy to women with the disease. The failure to prevent the incidence from continuing to rise represents to a great extent the failure to understand the precise mechanisms of breast carcinogenesis and the role of risk determinants whose alteration in society could lead to a reduced risk of developing the disease. The declines seen in mortality represent a considerable success, but there is no room for complacency until research can impact positively on reducing incidence.     

Bayesian methodology: an alternative to regular medical practice

The Bayes theorem provides a formula to calculate the probability of an event to occur conditioned by the occurrence of an anterior one (conditioned probability). In medicine it has been applied to calculate the probability of suffering a disease when having a positive result in a given test. This formula emphasizes the importance of prevalence of a disease (or a priori probability of the positive predictive value of a diagnostic test). The novelty of applying the bayesian methodology in clinical practice results from taking into consideration previous external information (or "a priori probability"), and to calculate how it is modified by the evidence (or "verisimilitude") provided by certain empirical tests, to obtain a new probability conditioned by the empirical evidence (or "a posteriori probability"). It also allows to perform sequential analysis (repeated observation of a given event a number of times not fixed in advance) and to incorporate the subjective probabilities to the reasoning. Some authors have proposed the use of bayesian methodology in research studies, such as clinical trials. Nevertheless, this methodology does not adapt well to this kind of reasoning which is hypothetical-deductive.     

Preparation of a skeletal muscle ventricle in sheep: severe damage to the Latissimus dorsi muscle due to mobilization before preconditioning

As part of a study examining the use of a skeletal muscle ventricle for cardiac assistance in sheep, a new concept of muscle preconditioning was put into practice. We aimed to produce a latissimus dorsi muscle (LDM) capable of performing chronic work immediately after the construction of a skeletal muscle ventricle. The left LDM was detached from the thoracic wall, divided longitudinally and reattached in situ to achieve vascular delay. The right LDM was left unaffected. Thereafter, preconditioning of both LDM was started according to the clinically approved stimulation protocol for cardiomyoplasty. Preconditioning of the unaffected right LDM in situ resulted in a complete muscle fiber transformation with no signs of degeneration or necrosis. Mobilization of the left LDM before preconditioning led to a distinct damage of the muscle. During conditioning, the increase in burst duration from 2 to 3 impulses in sheep A and from 3 to 5 impulses in sheep B resulted in a homogenous degeneration of the muscle fibers of the left LDM. Histomorphological analysis showed a dramatic increase in the percent perimysial and endomysial connective tissue. The applied concept of muscle prefabrication proved to be a failure. Muscle splitting and mobilization followed by vascular delay and in situ conditioning as a concept of muscle prefabrication should be strictly avoided.     

Pathogenesis of refractory secondary hyperparathyroidism

Calcitriol is currently used to reduce parathyroid hormone (PTH) levels in uremic patients. However, a significant number of patients fail to respond to calcitriol therapy. The data suggest that a poor response to calcitriol can be anticipated in patients with severe hyperparathyroidism (with a high basal PTH levels) and uncontrolled serum phosphate. The abnormal parathyroid response to calcitriol in uremic patients with severe parathyroid hyperplasia may be attributed, to a large extent, to the development of nodular hyperplasia as a result of clonal transformation from a diffuse polyclonal hyperplasia. The factors involved in the development of polyclonal parathyroid hyperplasia, at earlier stages of secondary hyperparathyroidism, appear to be the same factors that stimulate PTH secretion and synthesis: hypocalcemia, hyperphosphatemia and low serum calcitriol levels. Studies performed in vitro using parathyroid tissue from uremic patients who required parathyroidectomy demonstrate that in nodular hyperplasia there is an abnormal response to calcium and calcitriol, which suggests that there are factors intrinsic to the hyperplastic cell (such as decrease in calcium sensor receptors and vitamin D receptors) responsible for an abnormal regulation of parathyroid function. Accumulation of phosphate is a key factor in the pathogenesis of secondary hyperparathyroidism and a poor response to calcitriol treatment is associated with the failure to control the serum phosphorus. High phosphate stimulates PTH secretion as demonstrated by in vivo and in vitro studies. In addition, animal studies strongly suggest that phosphate increases parathyroid cell proliferation. There are growth-related genes potentially involved in uremic hyperparathyroidism; however, changes in the expression of these genes may be the consequence rather than the cause of parathyroid hyperplasia.     

Discharging to a nursing home: not a terminal event--a follow-up study of senior motor vehicle crash patients

Discharge to a nursing home (NH) because of chronic debilitating diseases or old age is generally a terminal event. The purpose of this study was to evaluate the NH outcome of senior citizens injured in motor vehicle crashes (MVC) discharged to a NH. From 2000 through 2004, 157 patients 75 years and older were admitted to the hospital for MVC. Of these, 32 patients were discharged to a NH, and these patients or their proxies were interviewed by telephone in June 2005 to request information as to driving status before and after the MVC, feeding, expression, and locomotion status, and/or date of death. After discharged from the NH, 72 per cent (23/32) of the patients lived at home, 52.2 per cent (12/23) among the drivers returned to drive, and those with functional impairments (excluding the five NH deaths and four still remaining in a NH) at the time of hospital discharge had 100 per cent or partial improvement in three functional independent measures at the time of the interview: 5 cases in feeding, 2 in expression, and 20 in locomotion. Eleven of the 20 individuals dependent or partially dependent in locomotion status were fully independent. The majority of the senior patients discharged to a NH after a MVC returned to a normal life by going back home, driving again, and regaining functional activities after NH discharge. Discharge to a NH for elderly MVC trauma patients may be regarded as a stepping-stone to independent living rather than a final resting place.     

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.     

Synovial osteochondromatosis of the elbow

We present 12 patients with synovial osteochondromatosis of the elbow treated by synovectomy. Histological review showed that seven cases were primary and five secondary osteochondromatosis. The patients with primary disease had a mean improvement in the flexion arc from a preoperative value of 40 degrees to 123 degrees to 5 degrees to 128 degrees when reviewed at a mean of nine years after operation. The secondary group had a mean improvement in the flexion arc from a preoperative value of 21 degrees to 98 degrees to 4 degrees to 131 degrees at a mean of 6.8 years after operation. There was recurrence in two of seven patients in the primary group and three of five in the secondary group. Osteoarthritis developed in six elbows in the primary and in three in the secondary group. Osteoarthritis secondary to synovial osteochondromatosis is progressive. In the established condition, the distinction between primary and secondary disease may be of greater histological than clinical relevance.