Severe muscle trauma triggers heightened and prolonged local musculoskeletal inflammation and impairs adjacent tibia fracture healing.

OBJECTIVES: Complicated fracture healing is often associated with the severity of surrounding muscle tissue trauma. Since inflammation is a primary determinant of musculoskeletal health and regeneration, it is plausible that delayed healing and non-unions are partly caused by compounding local inflammation in response to concomitant muscle trauma. METHODS AND RESULTS: To investigate this possibility, a Lewis rat open fracture model [tibia osteotomy with adjacent tibialis anterior (TA) muscle volumetric muscle loss (VML) injury] was interrogated. We observed that VML injury impaired tibia healing, as indicated by diminished mechanical strength and decreased mineralized bone within the fracture callus, as well as continued presence of cartilage instead of woven bone 28 days post-injury. The VML injured muscle presented innate and adaptive immune responses that were atypical of canonical muscle injury healing. Additionally, the VML injury resulted in a perturbation of the inflammatory phase of fracture healing, as indicated by elevations of CD3(+) lymphocytes and CD68+ macrophages in the fracture callus at 3 and 14d post-injury, respectively. CONCLUSIONS: These data indicate that heightened and sustained innate and adaptive immune responses to traumatized muscle are associated with impaired fracture healing and may be targeted for the prevention of delayed and non-union following musculoskeletal trauma.

Suturable mesh better resists early laparotomy failure in a cyclic ball-burst model.

PURPOSE: The small bites surgical technique supported by the STITCH trial has been touted as a strategy for preventing early laparotomy dehiscence through greater force distribution at the suture-tissue interface. However, this hernia prevention strategy requires an alteration in the standard closure technique that has not been widely adopted in the USA. This study seeks to determine whether incorporating a mid-weight polypropylene mesh material into a hollow-bore surgical suture material will effectively increase the force distribution at the suture-tissue interface and potentially help prevent early laparotomy dehiscence in an ex vivo model. METHODS: A cyclic stress ball-burst model was used to compare suturable mesh (0 DuraMesh™) to conventional suture. After midline laparotomy, 28 porcine abdominal wall specimens were closed with either 0 DuraMesh™ or #1 polydioxanone double-loop suture. A custom 3D-printed ball-burst test apparatus was used to fatigue the repair on a MTS Bionix Load Frame. The tissue was repetitively stressed at a physiological force of 15-120 N cycled at a rate of 0.25 Hz for a total of 1000 repetitions, followed by a load to failure, and the maximal force was recorded. RESULTS: The mean maximal force at suture pull-through was significantly higher (p < 0.0095) in the 0 DuraMesh suture group (mean: 850.1 N) compared to the 1 PDS group (mean: 714.7 N). CONCLUSION: This ex vivo study suggests that using rational suture design to improve force distribution at the suture-tissue interface may be a viable strategy for preventing the suture pull-through that drives incisional hernia.

Effects of renal clearance on plasma concentrations of homovanillic acid. Methodologic cautions.

Recently, there has been considerable interest in plasma concentrations of homovanillic acid (HVA) in various psychiatric disorders. Homovanillic acid is a weak organic acid, and its excretion probably resembles that of other organic acids (eg, p-aminohippuric acid) that are actively secreted by the kidney. Alterations in renal plasma flow can affect clearance of organic acids, resulting in changes in plasma concentrations. In our study, concentrations of plasma HVA and urinary HVA (from 24-hour urine collections) were measured in 20 prepubescent boys who received 3 weeks of placebo, dextroamphetamine sulfate, and fenfluramine hydrochloride in a randomized, double-blind, counterbalanced study of the treatment of attention-deficit disorder. Plasma HVA concentrations were significantly lower during fenfluramine treatment than during amphetamine treatment. This difference, however, seemed to be caused by alterations in renal clearance of HVA rather than changes in production. Whole-body production of HVA, as indexed by total urinary HVA excretion, was unaffected by the different treatments, while renal clearance of HVA did differ significantly between amphetamine and fenfluramine treatment. It seems that alterations in renal clearance can affect plasma HVA concentrations, which should be taken into account when plasma HVA is studied.

Essential tremor in twins: an assessment of genetic vs environmental determinants of etiology.

OBJECTIVE: To determine the relative contribution of genetics and environment to essential tremor using a twin study method. METHODS: Twins with postural or kinetic tremor were identified by movement disorders specialists during the conduct of a study investigating PD in members of the National Academy of Sciences and National Research Council World War II Veteran Twins Registry. The diagnosis of essential tremor was made by consensus using established diagnostic criteria. RESULTS: A total of 196 twins had postural or kinetic tremor on examination. Of these, 137 had PD or had a twin with PD and were excluded from this study. Thirty-three others were excluded because of incomplete data for their twin. Sixteen twin pairs were identified in which at least one twin had essential tremor. Pairwise concordance in monozygotic twins was approximately two times that in dizygotic twins (0.60 monozygotic, 0.27 dizygotic). CONCLUSION: This pattern is consistent with a genetic cause of essential tremor. Because monozygotic concordance is not 100%, environmental factors may also play a role in the cause of the disease.

Smoking and Parkinson's disease in twins.

OBJECTIVE: To test the hypothesis that cigarette smoking protects against the development of PD. BACKGROUND: Smoking has been inversely associated with PD in many studies, but whether this reflects a biologic effect on the underlying disease process or merely confounding or selection bias remains uncertain. METHODS: The authors compared smoking histories in male twin pairs identified from the National Academy of Sciences--National Research Council World War II Veteran Twins Cohort. The amount of cigarettes smoked (in pack-years) was collected until the time of PD onset in the affected twin or until the time of death for the unaffected twin, whichever came first. Differences in pack-years smoked until PD onset and until 10 and 20 years before onset were compared using paired t-tests. Comparisons were made overall and stratified by zygosity and concordance for PD. To assess the role of shared environment, correlation for smoking behaviors was compared between pairs concordant and discordant for PD. RESULTS: Detailed smoking histories were available for 113 twin pairs in which at least one twin had PD (discordant pairs: 43 monozygotic [MZ], 50 dizygotic [DZ]; concordant pairs: 10 MZ, 10 DZ). Within-pair correlation for ever smoking was high in MZ pairs (phi = 0.47, p = 0.001) but not in DZ pairs (phi = 0.007, p = 0.96). In 33 discordant MZ pairs and 39 discordant DZ pairs in which at least one twin had smoked, the twins without PD smoked more than their brothers smoked (32.5 vs. 22.7 pack-years, p = 0.026). This was more marked in the MZ pairs (37.1 vs. 25.3 pack-years, p = 0.077) than in the DZ pairs (28.6 vs. 20.5 pack-years, p = 0.17). A similar relationship was seen when smoking dose was calculated only until 10 years before PD onset, suggesting that the lower dose of smoking in the twin with PD was not the result of early, undiagnosed disease. CONCLUSION: Within twin pairs, risk of PD is inversely correlated with the dose (in pack-years) of cigarette smoking. This effect is most pronounced in MZ twins, despite the high correlation for smoking. Because MZ twins are genetically identical and are similar behaviorally, this difference is unlikely to result from either genetic factors or environmental confounders. These results are compatible with a true biologic protective effect of cigarette smoking.

Hypervascular presentation of multiple myeloma involving the skull, demonstrated on encephaloscintigraphy.

We present two cases of myelomatous involvement of the skull. Correlative studies with routine radiography, angiography, and encephaloscintigraphy were performed. The areas of involvement of the skull were confirmed as autopsy. A mixed pattern of photon-deficient and photon-abundant lesions was noted. The clinician should be aware of such mixed patterns.

The relative buffering power of cardioplegic solutions.

Those factors that prolong myocardial tolerance to global ischemia constitute an important prerequisite for effective cardioplegia. This study contrasts the relative buffering power of bicarbonate-based and tromethamine-based hyperkalemic crystalloid cardioplegic solution with histidine protein-type buffer (Bretschneider) solution. In addition, the solutions were compared with titration of whole blood and myocardial muscle homogenate.

Prophylactic tranexamic acid decreases bleeding after cardiac operations.

Thirty-eight patients undergoing a cardiac operation randomly received either tranexamic acid, a potent inhibitor of plasminogen, or placebo in an effort to determine whether prophylactic antifibrinolytic therapy reduces chest tube drainage. Twelve-hour blood loss was 750 +/- 314 (standard deviation) ml in the placebo group and 496 +/- 228 ml in the drug group (p = 0.0057). Fibrin split products were present more frequently in patients in the placebo group (17 of 20 compared with four of 18 in the drug group; p = 0.0002). Tranexamic acid markedly decreased plasminogen availability (112 +/- 104 units in the placebo group versus 36 +/- 18 units in the drug group, p = 0.0058). Plasma fibrinogen concentrations were similar in the placebo and drug groups. Patients in the placebo group received more fresh-frozen plasma and more mediastinal shed blood than those in the drug group. No coagulation-related complication occurred in the group receiving tranexamic acid. We conclude that prophylactic tranexamic acid can be administered safely to inhibit fibrinolysis during cardiac operations, decrease postoperative bleeding, and possibly decrease the frequency of blood product transfusion.

Development of a computer-assisted instructional tool for evaluation and treatment of renal masses. An experiment in hypermedia.

RATIONALE AND OBJECTIVES: Using a personal computer and a commercially available "authoring" application, the authors constructed an interactive hypermedia teaching tool for the evaluation and management of renal masses. METHODS AND RESULTS: Through a series of questions, images, illustrations, hypertext, and graphical flow charts, the user reviews the spectrum of renal masses, including neoplasms, inflammatory disease, cysts, and "pseudomasses." The various imaging modalities (computed tomography [CT], ultrasound [US], magnetic resonance imaging [MRI], and angiography) are illustrated, with selective advantages and disadvantages to each technique highlighted. Selected algorithms for evaluation and treatment of masses are provided. Text, questions, a teaching file, and algorithms form the major sections of the program. Numerous links within and between the major sections of the program, a capacity unique to hypermedia, allow for nonlinear entry into the program, tailored to the individual user. CONCLUSIONS: Preliminarily, medical students and residents have responded positively to this hypermedia project. Furthermore, their comments and criticism have provided important feedback for future updates and enhancements.

Blood flow to experimental renal tumors.

Radiolabeled microsphere techniques were used to measure renal blood flow (RBF) in rabbit kidneys with 14- to 16-day-old experimentally induced renal tumors. VX-2 carcinoma cells (25 microliters) harvested from carrier animal intramuscular tumors were injected supraselectively into an intralobar artery using fluoroscopically guided transcatheter techniques. Within 2 to 3 weeks, all animals developed localized 10 to 25 mm diameter renal tumors. Renal blood flow was calculated after left ventricular injection of 113Sn-labeled 15 mu diameter microspheres. Blood flow (ml/minute) in tumor-bearing kidneys (26.91 +/- 1.86) was significantly lower (P = less than .05) than in normal controls (49.79 +/- 7.71). The tumor-bearing kidneys were also significantly larger (15.21 +/- 1.27 gm) than control animal kidneys (10.89 +/- 0.071 gm). Analysis of the tumor kidneys showed flow (ml/minute/g) in the tumor-containing sections (1.82 +/- 0.15) and in the actual tumor tissue (0.62 +/- 0.07) to be significantly lower (P = less than .05) than (1) in the nontumor portions of the same kidneys (2.58 +/- 0.28), and (2) in the tumor animals' contralateral nontumor-bearing kidneys (3.22 +/- 0.16), and (3) in normal control animal kidneys (4.54 +/- 0.29). The reduced flow in tumor-bearing kidneys was not an artifact due to arteriovenous shunting, as demonstrated by 99mTc-microsphere studies in four additional tumor-bearing animals. This study has shown that blood flow to the tumor is extremely low compared with nontumor-containing ipsilateral, contralateral, and normal control renal tissue. These results provide important information relative to possible experimental therapeutic research involving embolization or pharmacologic manipulation of the blood supply to potentiate intra-arterial chemotherapy.

Renal cell carcinoma in pregnancy: report of three cases and review of the literature.

BACKGROUND: Renal cell carcinoma is a potentially fatal tumor that occasionally presents during pregnancy. Based on our experience with three patients and a review of the recent cases in the literature, we believe there has been a change in presentation of this lesion over that described in previous reviews. CASES: Two of three women with renal cell carcinoma found during pregnancy had symptoms suggesting recurrent urinary tract infection. The renal tumors were all discovered by ultrasound. In addition, magnetic resonance imaging was used for preoperative, intragestational staging of one patient. CONCLUSION: Renal cell carcinoma should be considered in women of childbearing age who present with recurrent or refractory urinary tract symptoms, flank pain, or a palpable flank mass. Ultrasound appears to be the imaging procedure of choice for evaluating the urinary system in pregnant women.

Prevention of retrograde cardioplegia catheter displacement.

The most frequent catheter-related complication of retrograde cardioplegia, in our experience, has been catheter displacement. An easily placed coronary sinus snare that maintains proper retrograde catheter position is described.

Coronary artery bypass grafting in patients who require long-term dialysis.

BACKGROUND: Should coronary artery bypass grafting (CABG) be performed in patients on long-term dialysis? This subject has been debated for several years. We retrospectively reviewed the charts of all patients who had CABG from August 1989 to October 1997. METHODS: We identified 70 patients who were on long-term dialysis and had CABG during that time period. Patients were evaluated by chart review and telephone survey. Forty-nine patients (70%) had unstable angina and 37 patients (52%) had triple vessel disease. Patient risk factors included 60 patients with hypertension (85%), 40 patients with diabetes mellitus (57%), 35 patients who had congestive heart failure (50%), 35 patients who had a previous myocardial infarction (50%), and 31 smokers (44%). Operative procedures included 49 patients who had CABG only and 21 patients who had concomitant CABG with valve replacement or repair. During the postoperative period, complications developed in 50% of patients. RESULTS: Review of these complications showed that 25% of patients required prolonged mechanical ventilation, and 10% of patients had septicemia. Operative mortality was high, with 10 patient deaths (14.3%) within 30 days of the procedure. Six (60%) of these deaths occurred in patients who had CABG and valve repair or replacement. Long-term follow up at 50.3 months showed no improvement in survival in patients who had CABG compared with the known mortality rate of 22% per year in dialysis patients regardless of comorbid conditions. Quality of life subjectively improved in only 41% of patients in follow-up telephone survey. CONCLUSIONS: Patients requiring long-term dialysis with coexistent severe cardiac disease should be thoroughly evaluated preoperatively. One must weigh the high morbidity and mortality risk against the limited long-term resolution of angina and ultimate survival.

Axillary artery cannulation in acute ascending aortic dissections.

BACKGROUND: Standard cannulation of the femoral artery in preparation for repair of a dissection involving the ascending aorta carries a high risk of malperfusion. Arterial perfusion through the right axillary artery is more likely to perfuse the true lumen and should be advantageous in acute dissections involving the ascending aorta. METHODS: Thirteen patients underwent repair of acute ascending aortic dissections and were perfused through the right axillary artery. All had deep hypothermic circulatory arrest. RESULTS: There was one mild intraoperative cerebrovascular accident with complete recovery and one operative death secondary to low cardiac output. There were no intraoperative problems with perfusion through the axillary artery, and there were no postoperative problems or complications involving the axillary artery, axillary vein, or brachial plexus. CONCLUSIONS: Arterial perfusion through the right axillary artery is a safe and effective means of more reliably perfusing the true lumen. In this regard, it may be superior to femoral artery perfusion and could lead to improved outcomes with repair of acute deBakey type I and II aortic dissections.

Augmented femoral venous return.

We present a technique of femoral cardiopulmonary bypass that allows excellent venous drainage. This is accomplished by augmenting the venous return with a centrifugal pump.

Combined cardiac operation and carotid endarterectomy during aortic cross-clamping.

We present a surgical technique that we believe provides superior cerebral protection for simultaneous correction of carotid and cardiac pathology with low operative mortality and stroke rate. Our study population consists of 23 consecutive patients undergoing cardiac operation between August 1989 and April 1991 who also had associated critical (greater than 85%) carotid artery stenosis. Using 20 degrees C systemic hypothermia for cerebral protection, we performed simultaneous correction of both lesions during the aortic cross-clamp period, using continuous retrograde blood cardioplegia for myocardial protection. Mean patient age was 69.4 years; 83% were 65 years or older. Eighty-seven percent had angina, 35% had recent myocardial infarctions (within 30 days), and 52% had congestive heart failure. Asymptomatic bruit was found in 39%, and 61% had previous strokes, neurologic symptoms, or both. All had 85% or greater luminal narrowing on cerebral angiography, with 65% having severe or critical contralateral disease as well. Sixty-one percent had associated other vascular pathology, including peripheral vascular occlusive disease, renal artery stenosis, or abdominal aortic aneurysm. There were no postoperative strokes or neurologic events. One early vein graft occlusion resulted in postoperative myocardial infarction and subsequent death (4.3%).

Circumflex artery ventricular fistula and pseudoaneurysm after mitral reoperation.

Prosthetic mitral valve reoperation complicated by atrioventricular groove pseudoaneurysm and circumflex ventricular fistula is presented. Ligation of the circumflex artery during mitral valve replacement is implicated after review of a previous cardiac angiogram.

Simultaneous carotid endarterectomy and coronary revascularization.

BACKGROUND: Combined cardiac operation and carotid endarterectomy using our technique is an acceptable approach to simultaneous correction of both carotid and cardiac disease. METHODS: From August 1989 to March 1998, 121 consecutive patients underwent combined operations. Of these patients, 112 had coronary artery bypass grafting and carotid endarterectomy, and 9 had coronary artery bypass grafting, carotid endarterectomy, and valve repair or replacement. All patients had a critical stenosis of 85% or more of the carotid artery. Mean age of the patients was 69.2 years; 80 patients were 65 years old or older. There were 88 men and 33 women. Notable risk factors included chronic obstructive pulmonary disease (19.8%), congestive heart failure (28%), preoperative myocardial infarction and unstable angina (66.9%). Of the patients, 20.7% had a stenosis of greater than 50% of the left main coronary artery. The technique used was correction of both the carotid and coronary lesions during a single aortic cross-clamp period using retrograde continuous blood cardioplegia for myocardial protection. Systemic hypothermia to 25 degrees C was used for cerebral protection. RESULTS: Mean cross-clamp time was 118 minutes. Seven patients (5.8%) sustained perioperative cerebrovascular accidents. Two patients had transient ischemic attacks. The procedure-related mortality rate was 5.8%. CONCLUSIONS: The described technique is a good method for simultaneous repair of coronary and carotid lesions in a high-risk group of patients with concomitant disease. We will continue to use it.

Clinical outcomes after aortic valve replacement with the Toronto stentless porcine valve.

BACKGROUND: Hemodynamic benefits of the Toronto stentless porcine valve have been documented. Clinical well-being and freedom from major valve-related events have been less well defined. METHODS: A total of 447 patients were prospectively followed for up to 8 years (1,745.2 valve years total, 3.9 valve years/patient). The patient demographics included 66% men, mean age 65 years, New York Heart Association functional class III-IV 55%, concomitant coronary artery bypass grafting 41%. RESULTS: We found that 83.7% of patients were in New York Heart Association functional class I and 80.8% had 0 to 1+ aortic insufficiency. Mean gradient at 6 years (n = 75) was 4.4 mm Hg and mean effective orifice area (EOA) 2.4 cm2. Late adverse event rates per patient per year were: embolism 1.0%, endocarditis 0.4%, thrombosis 0%, structural deterioration 0.2%, explant 0.3%, and valve-related death 0.6%. Freedom from valve-related death at 6 years was 95.8%; from cardiac death 96.3%. Freedom from endocarditis was 98.4%, from embolism 93.9%, from structural deterioration 97.4%, and freedom from explant 98.1%. For patients older than 60 years, freedom from structural deterioration was 100%. CONCLUSIONS: These results confirm satisfactory clinical outcomes after aortic valve replacement with the Toronto stentless porcine valve, with a low incidence of valve-related adverse events as long as 96 months after valve replacement.