Search PubMed⌕ Search

Biomedical subjects

D S Mulder

Publications and source records attributed to D S Mulder.

At least 37 records · Page 2Linked to original sources

Double-lung transplantation in mechanically ventilated patients with cystic fibrosis.

Many lung transplant programs consider ventilator dependence as a contraindication for transplantation. Among 54 patients in whom bilateral lung transplantations for cystic fibrosis were performed by the Joint Marseille-Montreal Lung Transplant Program, 10 were ventilator dependent. Three of them died in the early postoperative period (30%): 2 as a result of cerebral anoxia and sepsis, 1 of Pseudomonas cepacia pneumonia. Two patients died at 15 and 19 months after transplantation of obliterative bronchiolitis and secondary bacterial pneumonitis. Another 2 patients in whom obliterative bronchiolitis developed underwent retransplantation with a heart-lung block; 1 of those was operated on at 12 months and is well at 29 months after his initial transplantation; the second was operated on at 34 months and died of primary graft failure. Three other patients are alive and well at 3, 11, and 14 months after transplantation. Actuarial survival at 1 year was 70%. The postoperative course and the infectious and rejection complications were no different from those in patients who underwent transplantation while spontaneously breathing. Obliterative bronchiolitis developed in 66% of patients at risk (2 of 6 patients surviving more than 6 months). We conclude that transplantation in mechanically ventilated patients with cystic fibrosis is not associated with an increase in morbidity or mortality after bilateral lung transplantation. Long-term survival, as in patients who undergo transplantation while spontaneously breathing, is limited by the development of obliterative bronchiolitis.

Adolescent↗

Pain management principles and anesthesia techniques for thoracoscopy.

Thoracic surgeons have recently pursued innovative techniques that can help minimize postoperative pain. These have taken two basic directions. The first consists of a modification of the operative procedure itself, such that the surgical insult and hence the resulting pain are minimized. Modifications of the conventional thoracotomy technique have led to the development of the muscle-sparing thoracotomy and the linear or small transaxillary thoracotomy. The ultimate modification has been video-assisted thoracic surgery techniques, which are associated with a marked reduction in postoperative pain. The second approach centers on techniques that improve postoperative pain control. The recently published Agency Health Care Policy and Research guidelines provide a comprehensive review of the therapeutic options for postoperative pain control. These guidelines emphasize the value of nonsteroidal antiinflammatory drugs in conjunction with opioids as the preferred form of analgesia. Many authors have advocated the induction of spinal analgesia after thoracotomy, using either epidural opioids or local anesthesia, or both. Patient-controlled analgesia and multiple intercostal nerve blocks are other methods for managing postthoracotomy pain. The potential benefits conferred by aggressive pain control after thoracotomy are enormous for the patients, the surgeons, and the entire health-care system.

Analgesia↗

Thoracoscopy in Europe: views from North America.

A 4-month "minisabbatical" (June through September 1992) provided me with a selected view of the current status of thoracoscopic surgery as it is being performed in Europe. This experience comprised visits to three countries and a total of five clinical units doing endoscopic surgery. Observations are grouped into five categories: (1) the clinical spectrum of thoracoscopic procedures, (2) operating room design, (3) the evolution of instrumentation and imaging, (4) educational programs, and (5) strategies for testing innovative technologies. This short visit convinced me of the need for greater communication with our European colleagues.

Canada↗

Video-assisted thoracoscopic wedge resection of T1 lung cancer in high-risk patients.

OBJECTIVE: This study assessed the reliability and safety of VATR for treatment of peripheral T1 lung cancer in high-risk patients. SUMMARY BACKGROUND DATA: Surgical resection is the best therapy for stage I lung cancer. Patients with poor cardiopulmonary status or those who are elderly (> 75 years of age) are considered to be at high risk from thoracotomy and are frequently referred for radiation therapy or expectant palliative management. Data from previous studies suggest that survival with wedge resection is similar to that with lobectomy. The authors propose VATR, which is minimally invasive, as a therapeutic option in patients considered to be at high risk for resection by thoracotomy. METHODS: Between November 1990 and November 1992, more than 400 thoracoscopic lung resections were performed. Thirty patients with poor pulmonary function (forced expiratory volume FEV1] < 1 L or < 35% predicted; arterial oxygen tension [PaO2] < 60 mmHg on room air; diffusion capacity [DCO] < 40%) underwent 31 VATRs (1 patient had a staged procedure for bilateral synchronous lung cancers). All patients had T1 peripheral lesions with no bronchoscopically visible lesions. Computed tomography of the chest revealed no evidence of mediastinal disease in all patients. RESULTS: Patients had a mean FEV1 value of 0.9 L (38% predicted) and a mean age of 71 years. Tumors were located in left upper lobe (LUL) in 13 patients, in right lower lobe (RLL) in 7 patients, in right upper lobe (RUL) in 6 patients, in left lower lobe (LLL) in 4 patients, and in right middle lobe (RML) in 1 patient. Computed tomography-guided wire localization, methylene blue surface injection, and intraoperative ultrasonography were used to assist in defining difficult lesions. All lesions were successfully resected without converting to thoracotomy. One patient died on the 34th postoperative day of myocardial infarction (operative mortality rate of 3%). Five patients had prolonged air leaks (< 5 days), with a median chest tube time of 3 days. Two patients experienced pneumonia. CONCLUSION: The authors concluded that VATR is a safe and reliable procedure for treatment of peripheral T1 lung cancer in high-risk patients. Long-term follow-up will be required to determine the efficacy of this procedure regarding survival and locoregional recurrence.

Aged↗

Impact of on-site care, prehospital time, and level of in-hospital care on survival in severely injured patients.

A sample of 360 severely injured patients was selected from a cohort of 8007 trauma victims followed prospectively from the time of injury to death or discharge. A case referent study was used to test the association between on-site care, total prehospital time, and level of care at the receiving hospital with short-term survival. Multiple logistic regression analyses showed that use of Advanced Life Support (ALS) at the scene was not associated with survival, whereas treatment at a level I compatible hospital was associated with a 38% reduction in the odds of dying, which approached statistical significance. Total prehospital time over 60 minutes was associated with a statistically significant adjusted relative odds of dying (OR = 3.0). The results of this study support the need for regionalization of trauma care and fail to show a benefit associated with ALS.

Adult↗

Lectin-dependent cell-mediated cytotoxicity and natural killer function in rejecting and infected lung allografts.

Differentiation between rejection and infection of lung allografts remains difficult. The effects of these two pathologic entities on the cytolytic activity of bronchoalveolar lavage (BAL) and PBL were investigated. Left lung allotransplantation was performed on 16 mongrel dogs of which 12 were available for complete studies. All animals received CA, AZA, and PRED for 2 weeks. Four grafts developed left lower lobe Gram negative pneumonia. The eight remaining recipients progressed gradually to severe rejection after acute reduction of immunosuppression. Cytolytic activity of blood and left lung BAL lymphocytes was quantitated by the natural killer (NK) and lectin-dependent cell-mediated cytotoxicity (LDCMC) assays. Two additional groups serving as controls were either given a 10-day course of immunosuppressants or had right lower lobe pneumonia induced by transbronchial inoculation of gram negative bacteria. Immunosuppressed control animals showed significant depression of PBL and BAL lymphocyte LDCMC and NK activity. Similarly, BAL lymphocytes expressed very low LDCMC in normal allografts (2.8 +/- 0.8%). Once rejection developed and progressed, LDCMC became significantly higher (15.6 +/- 2.2 and 52.7 +/- 2.8% in mild and severe rejection, respectively). There was no detectable NK activity in rejecting lung allografts. BAL lymphocytes from infected allografts, on the other hand, showed an elevation of both NK and LDCMC activity (9.1 +/- 1.1 and 14.6 +/- 1.0%, respectively). Similarly, bacterial pneumonia in control animals manifested an increase in NK and LDCMC activity in lung and blood. PBL lymphocytes of lung allograft recipients, however, had increased NK and LDCMC activity in both rejection and infection. LDCMC/NK activity ratio (LM/NK index) of lung lymphocytes was significantly higher in rejecting allografts (11.2 +/- 1.0 and 12.4 +/- 1.6 for mild and severe rejection, respectively) than in infected ones (1.2 +/- 0.3, P < 0.0001). It appears, from this study, that rejection of the lung allograft results in alterations in BAL lymphocyte phenotypes and functions that differ from those associated with bacterial infection. Such differences may be useful in distinguishing episodes of acute allograft rejection from bacterial infection.

Animals↗

Effect of cardiopulmonary bypass on circulating lymphocyte function.

Extracorporeal cardiopulmonary bypass (CPB) has been associated with a wide variety of immunological derangements, including a transient postoperative impairment of lymphocyte function. We examined changes in phenotypic and nonspecific cytotoxicity of peripheral blood mononuclear cells after extracorporeal CPB. The peripheral blood samples obtained from 10 patients were subjected to natural killer and cytotoxic T lymphocyte activity assay before and at intervals after CPB. Phenotypic analysis of peripheral blood lymphocytes was performed in 5 patients before and immediately after CPB. We observed a significant increase in peripheral blood CD8+ cells (cytotoxic/suppressor T lymphocytes) (16.1% +/- 2.5% versus 22.5% +/- 2.1%; p less than .005) and a decrease in CD4+ cells (helper/inducer T lymphocytes) (46.1% +/- 3.5% versus 36.1% +/- 3.5%; p less than 0.02) immediately after extracorporeal circulation. The CD8/CD4 ratio in peripheral blood was significantly increased immediately after bypass (0.53 versus 0.80; p less than 0.001). No significant changes in percentages of other leukocyte subsets in peripheral blood were noted. The activity of cytotoxic T lymphocytes and natural killer cells in peripheral blood was impaired on postoperative days 1 and 3 but was restored to preoperative values by removal of mononuclear phagocytes from these cells. The decrease in natural killer cell and cytotoxic T lymphocyte activity in peripheral blood may signify a temporary impairment of the effector arm of the cell-mediated immunity in the post-operative period. The observed changes in peripheral blood phenotype and function may be involved in early organ injury and infectious complications after CPB.

Adult↗

Double-lung transplantation for cystic fibrosis. The Cystic Fibrosis Transplant Study Group.

One hundred twenty cystic fibrosis patients were accepted for transplantation. Twenty-five patients underwent double-lung transplantation. Twenty-five patients died awaiting transplantation (20.6%). There were 13 female and 12 male patients. Their mean age was 28 years (range, 7 to 34 years), and mean percentage ideal body weight was 76% (range, 58.5% to 91.9%). Most patients were hypoxic and hypercarbic. Two patients underwent tracheal anastomosis, 15 had en bloc bronchial anastomoses, and 8 had sequential single-lung transplants. Operative mortality was 16%; all deaths were related to bleeding from extensive adhesions. Actuarial survival at 1 year was 64%. Rejection and infection were frequent during the first month and decreased thereafter. Airway complications occurred in 5 patients but were amenable to laser therapy and stenting. We conclude that double-lung transplantation is an acceptable modality for the treatment of cystic fibrosis patients with end-stage lung disease. It may be a better alternative to heart-lung transplantation considering the paucity of thoracic organ donors.

Adolescent↗

Standardized mortality ratio analysis on a sample of severely injured patients from a large Canadian city without regionalized trauma care.

Flora's Z statistic and standardized mortality ratios (SMRs) as indicators of excess mortality were calculated for a sample of 355 patients with major trauma. A statistically significant overall excess mortality was observed in this sample (Z = 6.77, SMR = 1.81, p less than 0.05). Advanced life support provided by physicians at the scene (MD-ALS) was not associated with reduced excess mortality. A significant trend toward lower excess mortality was associated with a higher level of trauma care at the receiving hospital (p less than 0.05). Total prehospital time over 60 minutes was associated with a significant increase in excess mortality (p less than 0.001). These results support regionalization of trauma care and failed to show any benefit associated with MD-ALS.

Adolescent↗

The 1991 Fraser Gurd Lecture: evolution of airway control in the management of injured patients.

The evolution of methods for airway control has been an important factor in improving overall trauma care. Many important advances have been made in technique, tubes, and timing. Current methods of airway control are listed in Table 2 and are categorized as emergency or elective. It is always assumed that basic life support techniques will be in place before this hierarchic scheme for airway control is used. Unfortunately, hypoxemia continues to be a factor in preventable trauma deaths. There is much to be done in the future to further improve airway management in injured patients. There is an immediate need to assess methods of airway control in the pre-hospital phase using a randomized clinical trial. The ideal tube for cricothyroidotomy, tracheostomy, or endotracheal intubation remains to be designed. There is a need for further multicenter trials on the timing of tracheostomy in the critical care unit. The role of differential ventilators in the management of unilateral pulmonary parenchymal injury requires clinical validation. Intravascular membrane oxygenators have been proposed in advanced pulmonary insufficiency in a ventilated patient. Thus, while many important strides have been made in airway management following trauma, there remain great challenges in addressing the persistent problem of systemic hypoxemia after multiple injuries.

Emergencies↗

Phenotypic expression of bronchoalveolar lavage cells in lung rejection and infection.

The differentiation of episodes of lung allograft rejection from infection continues to be a problem. Bronchoalveolar lavage (BAL) has recently gained some success in the diagnosis and management of interstitial lung disease. To assess the usefulness of BAL in differentiating between lung allograft rejection and infection, we examined the differences in cellular subsets of BAL and peripheral blood (PBL) samples in a controlled canine model of rejection or pneumonia. Single-lung allotransplants were allowed to undergo rejection by withdrawing immunosuppressive agents (n = 6). In another group of dogs (n = 5), pneumonia was induced by transbronchial injection of Pseudomonas aeruginosa and melted agar followed by bronchial fulguration. Cells obtained from bronchoscopic BAL and PBL samples were labeled with functionally characterized cross-reactive murine monoclonal antibodies. Transthoracic needle biopsies and transbronchial biopsies were done to assess their adequacy in examining the rejecting or infected lungs and were compared with open lung biopsies. We found the following: (1) the percentage of DT2-labeled cells was significantly higher (p less than 0.05) in BAL samples from rejecting lungs compared with infected lungs; (2) the PBL/BAL ratio of DT2-labeled cell percentages was significantly higher in pneumonia (1.7 +/- 0.3) than rejection (0.5 +/- 0.2) (p less than 0.004); (3) the percentage of E11-labeled cells in PBL samples was significantly higher (p less than 0.02) in rejection than in infection; and (4) the ratio of WIG4 to DT2 cellular subset percentages in BAL samples from rejection (26.8 +/- 9.9) was significantly lower than from infection (61.0 +/- 22.9) (p less than 0.03). Transthoracic and transbronchial biopsies did not always yield representative specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Altered cellular immune function in the atelectatic lung.

Pulmonary atelectasis is common and may predispose the lung to infection. We have previously shown that atelectasis impairs alveolar macrophage antibacterial function. This study examines the effect of atelectasis on the cytotoxic function of lymphocytes harvested from the bronchoalveolar space of atelectatic lung segments by bronchoalveolar lavage. Specifically, we studied natural killer and lectin-dependent cell-mediated cytotoxicity in peripheral blood and bronchoalveolar lavage lymphocytes from the atelectatic lower lobes and contralateral normal lobes in a group of 8 dogs. We observed a decline of natural killer and lectin-dependent cell-mediated cytotoxicity to 62.7% and 61.5%, respectively, of preatelectasis control values in the affected lung lobes (p less than 0.01). Simultaneous measurements of cytotoxic activity of bronchoalveolar lavage lymphocytes harvested from the unaffected contralateral normal lungs were comparable with control values. On the other hand, natural killer and lectin-dependent cell-mediated cytotoxicity activities in peripheral blood lymphocytes were significantly increased in animals having right lower lobe atelectasis (166.7% and 154.7% of pretreated normal control, respectively, p less than 0.01). Atelectasis was also associated with an influx of polymorphonuclear leukocytes into the bronchoalveolar compartment. These findings confirm the presence of natural killer cells and cytotoxic lymphocytes in the bronchoalveolar compartment and demonstrate an atelectasis-induced impairment of local bronchoalveolar lymphocyte function. Such a dysfunction of local lung cellular host defenses may render the atelectatic lung susceptible to infection.

Animals↗

The reversibility of impaired mucociliary function after lung transplantation.

Impairment of mucociliary function occurs after lung transplantation and may predispose patients to repeated pulmonary infections. The purpose of this study is to determine whether and how soon such mucociliary function may recover. Ten dogs underwent left lung autotransplantation. Within 3 weeks five of these dogs underwent study for proximal airway clearance by observation through a bronchoscope of the movement of carbon particles placed at different locations on the tracheobronchial mucosa. The mechanical properties of collected mucus from specific sites were determined by magnetic rheometry. The right lung, which was not operated on, served as a paired control. Similar studies were conducted in the remaining five dogs at 12 weeks after autotransplantation. Lung autotransplantation caused significant depression of proximal airway clearance and a 35% increase in mucous rigidity (p = 0.05) soon after operation. At 12 weeks after operation, there was a partial recovery of proximal airway clearance. Mucous changes were no longer consistent. Histologic and electron microscopic examinations initially revealed focal denudation of ciliated cells and loss of the bronchial glands. At 12 weeks there was a regeneration of cilia and a reappearance of the bronchial glands. We conclude that the mucociliary function, observed to be depressed early after lung autotransplantation, recovers partially during the late postoperative period. Thus the mucociliary functional recovery should be attributed to revascularization rather than to reinnervation, since the latter is unlikely to occur during this period.

Anastomosis, Surgical↗

Warm ischemia induces alteration in lung immune cell functions.

Warm ischemia is an important factor in early allograft dysfunction. To elucidate cellular events involved in such lung injury, we examined the effects of warm ischemia on the cytotoxic function of lymphocytes retrieved by bronchoalveolar lavage as compared with peripheral blood lymphocytes. Warm ischemia of the lung was induced in eight dogs by crossclamping left hilar structures for 1 hour. Bronchoalveolar cells from ischemia left and unaffected right lungs, as well as blood lymphocytes, were isolated before operation and 2 hours, 72 hours, and 7 days after operation. Lung and blood lymphocytes were assayed for natural killer and lectin-dependent cell-mediated cytotoxicity. Warm ischemia resulted in a significant impairment of natural killer activity within 2 hours of reperfusion (49% of preoperative control cytolysis, p less than 0.01). There was a significant increase in natural killer activity in bronchoalveolar lavage mononuclear cells 72 hours after reperfusion injury (178.4% of preoperative value, p less than 0.01). Interestingly, these functional alterations were not paralleled with changes seen in the peripheral blood lymphocytes or the opposite nonaffected lungs, where the natural killer activity appeared significantly depressed at 72 hours. Similarly, lectin-dependent cell-mediated cytotoxicity was noted to be increased in the bronchoalveolar lavage from the ischemic lung (179.5%, p less than 0.01) but decreased in the bronchoalveolar lavage from the nonaffected lung and peripheral blood lymphocytes at 72 hours after injury. We conclude that warm ischemia is associated with a functional alteration of the local lung immune cells. Such alteration is not observed in cells from the opposite lung or peripheral blood. The observed increase in nonspecific cytotoxicity of bronchoalveolar lymphocytes can be causative in the early damage seen in poorly preserved lung allografts.

Animals↗

[Percutaneous endoscopic tracheostomy].

Between 6/88 and 8/89 61 critically ill patients (sepsis, ARDS, pneumonia, multiple trauma, etc.) underwent elective percutaneous endoscopic tracheostomy (PET). Following dilation up to 36 Fr. a number 6-10 tracheostomy tube was introduced. The patients were ventilated 17 (2-68 days) before and 28 (4-160) days after PET. One patient died from cardiac arrest, and in 4 patients, because of tube obstruction or cuff defect, reintubation was necessary. Additionally 2 significant infections and a minor bleeding and a emphysema occurred. Elective percutaneous tracheostomy performed in the ICU seems to be a simple and cost-effective procedure.

Coma↗

Endoscopic guided percutaneous tracheostomy: early results of a consecutive trial.

Percutaneous tracheostomy is increasingly being used for patients needing prolonged ventilatory support. The purpose of this study was to assess the feasibility of widespread application of endoscopic guided percutaneous tracheostomy. Sixty-one consecutive ICU patients requiring prolonged mechanical ventilation underwent bedside endoscopic guided percutaneous tracheostomy. Using a modified Ciaglia technique, a #6-10 tracheostomy tube was introduced between the second and third tracheal rings. Bronchoscopic transillumination facilitated identification of the appropriate tracheostomy site, and verified satisfactory placement of dilators and tracheostomy tube. There was one procedure-related death due to arrhythmia. Procedure-related complications included (n = 7): bleeding (controlled with local pressure), two infections, two cuff tears, and two obstructions of the tracheal tube. The tracheostomy was eventually removed in 13 patients. Bronchoscopic evaluation of three patients at 4 months post-tracheostomy removal was normal and there has been no clinical evidence suggestive of tracheal stenosis in the remaining ten extubated patients. There was a 50% reduction in cost when compared to operative tracheostomy. Percutaneous tracheostomy is a simple, safe, cost-effective bedside procedure for critically ill ventilator-dependent patients. Endoscopic guidance appears to increase the safety of this procedure and may prevent complications of pneumothorax, subcutaneous emphysema, and paratracheal false passage previously reported with blinded percutaneous methods.

Adult↗

Percutaneous endoscopic tracheostomy.

Bedside percutaneous tracheostomies are increasingly performed. This avoids patient transport to the operating room. Complications of this procedure are largely related to the blind nature of the technique. After laboratory studies, 4 patients underwent percutaneous endoscopic guided tracheostomy in a selective clinical trial. There were no procedure-related complications. Endoscopic guidance ensures precise low tracheostomy position, prevents paratracheal tube misplacement, and avoids inadvertent injuries.

Endoscopy↗

Does the surgical trauma of "exploratory thoracotomy" affect survival of patients with bronchogenic carcinoma?

A retrospective review was carried out to assess the possible adverse immunosuppressive effect of exploratory thoracotomy on the survival of patients with non-small cell carcinoma of the lung with N2 nodal metastases. Between 1960 and 1982, 48 patients with non-small cell bronchogenic carcinoma underwent exploratory thoracotomy; lung resection was not done because mediastinal lymph nodes were involved. The survival of these patients was compared with that of 64 patients in whom N2 disease was established by mediastinoscopy alone and who did not undergo thoracotomy. There were no significant differences with respect to age, sex, tumour type and adjunctive radiotherapy. There were slightly more T4 tumours in the thoracotomy group (50% versus 30%). The hospital stay was longer in the thoracotomy group (2.3 +/- 1.1 versus 1.5 +/- 0.9 months [mean +/- SD]). However, follow-up studies showed that, although these patients had a more traumatic procedure, the actuarial survival curves for the two groups were virtually identical, and the 12-month survival rates were less than 20% for both groups. The median survival was 6.0 months for the thoracotomy group and 7.0 months for the mediastinoscopy group. These findings failed to demonstrate an adverse immunosuppressive effect of thoracotomy on lung cancer patients.

Adult↗