The impact of diaphragm management on prolonged ventilator support after thoracoabdominal aortic repair

PURPOSE: The relationship of the division of the diaphragm during thoracoabdominal aortic repair to prolonged ventilator support has not been studied. The purpose of this study was (1) to determine whether preservation of diaphragm integrity has a significant effect on postoperative ventilator duration and (2) to elucidate other pulmonary risk factors related to thoracoabdominal aortic surgery and to study the relationship of these factors to the intact diaphragm technique. METHODS:Between February 1991 and January 1997, we repaired 397 descending and thoracoabdominal aortic aneurysms. Descending thoracic aneurysms were not included in the study because their repair does not include the diaphragm. A total of 256 patients participated in this study. The diaphragm was divided in 150 patients and left intact in 106 patients. Examined as potential risk factors were patient demographics, history and physical findings, aneurysm extent, urgency of the procedure, acute dissection, cross-clamp time, homologous and autologous blood product consumption, and adjunctive operative techniques. FEV1 also was considered in the 197 patients for whom preoperative spirometry was available. Prolonged mechanical ventilation was defined as ventilator support for >72 hours. Data were analyzed by univariate contingency table and multiple logistic regression methods. RESULTS: Increasing age (odds ratio [OR], 1.02/y; P <.02), current smoking (OR, 2.6; P <.0008), total cross-clamp time (OR, 1.0/min; P <.008), units packed red blood cells transfused (OR, 1.06/unit; P <.008), and division of the diaphragm (OR, 2.03; P <.02) were significant, independent predictors of prolonged ventilation. Sixty-seven percent of patients (71 of 106) whose diaphragms were preserved were extubated in <72 hours compared with 52% of patients (78 of 150) who underwent diaphragm division (OR, 0.53; P <.02). CONCLUSION: Independently of well known pulmonary risk factors, an intact diaphragm during thoracoabdominal aortic repair results in a higher probability of early ventilator weaning.     

Chronic inhibition of NOS does not prevent plasticity of rat somatosensory (S1) cortex following deafferentation

Nitric oxide (NO) has been proposed as an intercellular messenger mediating postsynaptic to presynaptic information transfer in the induction of long-term potentiation. A number of studies support the possible involvement of NO in synaptic plasticity. NO may have a role in synaptogenesis and synaptic plasticity in developing rat brain and may play a fundamental part in the process of regeneration, plasticity, and retargeting of axons following injury. We examined the possible role of NO on plasticity in the rat first somatosensory cortex with [14C]2-deoxyglucose (2-DG) autoradiography in rats treated daily with l-nitroarginine (l-NA) following neonatal unilateral vibrissae deafferentation. After 6 weeks of l-NA treatment, the local cerebral glucose utilization (LCGU) and the spatial extent of the metabolic activation following stimulation of the spared whisker was measured. NOS catalytic activity exhibited significant inhibition throughout the treatment period. Vibrissae deafferentation produced a small but not statistically significant increase of LCGU in the vibrissa activated C3 barrel, and l-NA treatment did not alter the activation of LCGU in the deafferented cortex following whisker stimulation. Additionally, l-NA treatment did not alter the area of metabolic activation on either the non-deafferented side or the deafferented side. Deafferentation produced a 298% increase in the metabolic representation of the spared C3 barrel following stimulation in the saline treated animals, a 257% increase in the chronically l-NA treated animals, and a 256% increase in the short-term treated animals, all with respect to the response in the non-deafferented cortex. Metabolic plasticity in the barrel cortex was not attenuated by l-NA treatment. These results show that nitric oxide does not play a major role on developmental cortical plasticity induced by vibrissae deafferentation in the rat.     

Kalirin inhibition of inducible nitric-oxide synthase

Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity.     

Polo-like kinase 1 as a target for human cytomegalovirus pp65 lower matrix protein

Human cytomegalovirus (HCMV) pp65 protein is the major constituent of viral dense bodies but is dispensable for viral growth in vitro. pp65 copurifies with a S/T kinase activity and has been implicated in phosphorylation of HCMV IE1 immediate-early protein and its escape from major histocompatibility complex 1 presentation. Furthermore, the presence of pp65 correlates with a virion-associated kinase activity. To clarify the role of pp65, yeast two-hybrid system (THS) screening was performed to identify pp65 cellular partners. A total of 18 out of 48 yeast clones harboring cDNAs for putative pp65 binding proteins encoded the Polo-like kinase 1 (Plk1) C-terminal domain. Plk1 behaved as a bona fide pp65 partner in THS control crosses, and the interaction was confirmed by in vitro binding experiments. Endogenous Plk1 was coimmunoprecipitated with pp65 from transiently transfected COS7 cells. In infected fibroblasts, Plk1 was coimmunoprecipitated with pp65 at late infection stages. Furthermore, Plk1 was detected within wild-type HCMV particles but not within the particles of a pp65-negative mutant (RVAd65). The hydrophilic region of pp65 was phosphorylated in vitro by Plk1. These results suggest that one function of pp65 may be to capture a cell kinase, perhaps in order to alter its activity, nucleotide preference, substrate specificity, or subcellular localization to the advantage of HCMV.     

Identification of seven Treponema species in health- and disease-associated dental plaque by nested PCR

Species-specific nested PCR was used to detect Treponema amylovorum, Treponema denticola, Treponema maltophilum, Treponema medium, Treponema pectinovorum, Treponema socranskii, and Treponema vincentii in dental plaque. Subjects with periodontitis harbored all species, but T. pectinovorum and T. vincentii were not found in plaque from disease-free subjects.     

Endotoxin temporarily impairs canine jejunal absorption of water, electrolytes, and glucose

OBJECTIVE: To evaluate the usefulness of a portable, computer-based, oscillometric, noninvasive blood pressure monitor for the automatic surveillance of postoperative infrainguinal bypasses. DESIGN: Prospective unblinded study. SETTING: Regional tertiary care Veterans Affairs medical center. PATIENTS: A total of 60 limbs were examined in 3 groups (n = 20 in each group): normal, asymptomatic volunteers; older patients with symptomatic peripheral vascular disease; and patients who had undergone infrainguinal bypass procedures. INTERVENTIONS: Noninvasive blood pressure monitor pressures, complete lower extremity arterial studies with Doppler ankle-brachial index (ABI), segmental pressures, and pulse volume recordings were performed in all groups. The patients who had undergone surgery also had hourly noninvasive blood pressure measurements taken. MAIN OUTCOME MEASURES: Ankle-brachial indices obtained with the noninvasive blood pressure monitor were compared with simultaneous manual Doppler ABIs and pulse volume recordings. RESULTS: There was a significant overall correlation between the Doppler-derived ABIs and automatic oscillometric values (r = 0.89, P < .001). Although there was a slight difference in absolute values (+/-SEM) (0.90 +/- 0.03 vs 0.84 +/- 0.03, respectively), an excellent correlation was found between the 2 methods in the clinically relevant range of ABI values between 0.60 and 1.10. The oscillometric method, however, overestimated the ABI when it was less than 0.60 by the Doppler method (0.61 +/- 0.02 vs 0.44 +/- 0.03, P < .001) and underestimated it when it was more than 1.10 (1.05 +/- 0.02 vs 1.16 +/- 0.01, P < .001). (All values given as +/-SEM.) Oscillometric overestimation correlated with depressed pulse volume recording waveforms (P < .001) or diminished pulse volume recording amplitudes of less than 10 mm (P < .001). CONCLUSION: The automatic oscillometric monitor provides a useful, accurate, objective, and quantitative method for postoperative bypass graft surveillance.     

Rehabilitation of dogs with surgically treated cranial cruciate ligament-deficient stifles by use of electrical stimulation of muscles

OBJECTIVE: To determine effect of electrical muscle stimulation (EMS) on rate and degree of return to function of the limb and development of degenerative joint disease (DJD) after surgical creation and subsequent stabilization of the cranial cruciate ligament (CrCL)-deficient stifle. ANIMALS: 12 clinically normal adult large (19.5 to 31.5 kg) dogs. PROCEDURE: Dogs were anesthetized, and the right CrCL was severed via arthrotomy, destabilizing the stifle. After 3 weeks, the stifle was surgically stabilized. Three weeks later, 6 dogs were subjected to an EMS treatment protocol for the thigh muscles. At 5, 9, 13, and 19 weeks after stifle destabilization, treated (n = 6) and control (n = 6) dogs were evaluated for return of stifle function. Gross and histologic evaluations of the stifles were performed at 19 weeks after stifle destabilization. RESULTS: Treated dogs had significantly (P = 0.001) better lameness score than did control dogs. There was less palpable crepitation of the stifle in treated dogs (P = 0.06); treated dogs also had significantly (P = 0.01) fewer radiographic signs of bone changes. Thigh circumference was significantly (P = 0.02) larger in treated dogs. There was less gross cartilage damage (P = 0.07) in the EMS-treated dogs, but more medial meniscal damage (P = 0.058, cranial pole; P = 0.051, caudal pole). CONCLUSIONS: Improved lameness scores, larger thigh circumference, and decreased radiographically apparent bony changes observed for the treated group of dogs support the hypothesis that dogs treated by EMS after surgical stabilization of the CrCL-deficient stifle had improved limb function, with less DJD, than did dogs treated with the currently accepted clinical protocol of cage rest and slow return to normal activity. However, results of force plate evaluation did not support the hypothesis. Increased meniscal damage in dogs treated by EMS may be cause for concern.