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Biomedical subjects

J D Miller

Publications and source records attributed to J D Miller.

At least 199 records · Page 11Linked to original sources

Isolated lung transplantation.

A clinical reality since 1981, lung transplantation is now generally accepted as a useful procedure for patients with end-stage lung disease. Early attempts at lung transplantation were marked by infection, rejection, and, in particular, bronchial dehiscence. Obliterative bronchiolitis, an airway-targeted form of chronic rejection, continues to be a problem. It is associated with all types of lung transplantation and is an important cause of late death. In the past few years advances in surgical technique, organ preservation and postoperative management have all contributed to improved survival and preservation of lung function. The shortage of suitable organ donors remains the limiting factor in clinical programs worldwide and curtails more widespread application of lung transplantation.

Humans↗

Respiratory complications of renal infection.

We present a case report of pleural effusion and hypoxia developing in a nonpregnant woman with a renal abscess. Our review of the literature reveals that the other reported cases of respiratory complications of renal infections have all occurred in pregnant women.

Abscess↗

Unilateral donor lung dysfunction does not preclude successful contralateral single lung transplantation.

Single lung transplantation remains limited by a severe shortage of suitable donor lungs. Potential lung donors are often deemed unsuitable because accepted criteria (both lungs clear on the chest roentgenogram, arterial oxygen tension greater than 300 mm Hg with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 5 cm H2O, and no purulent secretions) do not distinguish between unilateral and bilateral pulmonary disease. Many adequate single lung grafts may be discarded as a result of contralateral aspiration or pulmonary trauma. We have recently used intraoperative unilateral ventilation and perfusion to assess single lung function in potential donors with contralateral lung disease. In the 11-month period ending October 1, 1990, we performed 18 single lung transplants. In four of these cases (22%), the donor chest roentgenogram or bronchoscopic examination demonstrated significant unilateral lung injury. Donor arterial oxygen tension, (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) was below the accepted level in each case (246 +/- 47 mm Hg, mean +/- standard deviation). Through the sternotomy used for multiple organ harvest, the pulmonary artery to the injured lung was clamped. A double-lumen endotracheal tube or endobronchial balloon occlusion catheter was used to permit ventilation of the uninjured lung alone. A second measurement of arterial oxygen tension (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) revealed excellent unilateral lung function in all four cases (499.5 +/- 43 mm Hg; p less than 0.0004). These single lung grafts (three right, one left) were transplanted uneventfully into four recipients (three with pulmonary fibrosis and one with primary pulmonary hypertension). Lung function early after transplantation was adequate in all patients. Two patients were extubated within 24 hours. There were two late deaths, one caused by rejection and Aspergillus infection and the other caused by cytomegalovirus 6 months after transplantation. Two patients are alive and doing well. We conclude that assessment of unilateral lung function in potential lung donors is indicated in selected cases, may be quickly and easily performed, and may significantly increase the availability of single lung grafts.

Brain Death↗

The significance of posttraumatic increase in cerebral blood flow velocity: a transcranial Doppler ultrasound study.

Using transcranial doppler ultrasonography, cerebral blood flow velocity was measured daily from both middle cerebral arteries in 121 patients who had suffered minor (n = 55), moderate (n = 16), or severe (n = 50) brain injury. Serial computed tomographic scans were performed to identify noncontusion-related infarction (NCI). Cerebral perfusion pressure was monitored continuously in 41 patients who had severe head injury; of these, 22 had continuous measurement of arterial and jugular bulb venous oxygen (SJO2) saturation. Abnormally high mean flow velocity (greater than 100 cm/s) was observed in 23 patients (minor injury, n = 3; moderate injury, n = 3; severe injury, n = 17), but was recorded only when cerebral perfusion pressure exceeded 60 mm Hg (P less than 0.0001). Fourteen patients who underwent SJO2 monitoring developed increased mean flow velocity (MFV). In 6, the arterial-jugular venous oxygen content difference (AVDO2) was below 4 ml/dl, indicating global cerebral hyperemia. All had bilateral elevation of MFV, and 6 of the 8 nonhyperemic patients (AVDO2, 4-9 ml/dl) had a unilateral increase of MFV (P = 0.018). Four of the 23 patients with increased MFV developed NCI, as compared with none of the patients without elevated MFV (P = 0.015). All patients with NCI had suffered severe brain injury, had unilateral elevation of MFV in the terriory of the relevant cerebral vessel, and had received therapy to correct reduced cerebral perfusion pressure (P = 0.008). NCI did not occur in any patient with increased MFV that was associated with global hyperemia.

Adolescent↗

Control of intracranial pressure in patients with severe head injury.

Raised intracranial pressure (ICP) occurs at some time in 50-75% of severely head injured patients. Measurement of ICP alone is not sufficient. Arterial pressure must also be monitored: the important physiological variable is cerebral perfusion pressure. Detailed analysis of the ICP recording yields valuable information on the nature and cause of ICP, with implications for appropriate therapy. Additional measurements of importance include brain electrical activity, arterial and jugular venous oxygen saturation, and blood flow velocity in major intracranial arteries measured by transcranial Doppler sonography. These assessments not only add information about the cause of intracranial hypertension (vascular vs. nonvascular) but also help to regulate therapy, providing early warning that a treatment for reducing the ICP is actually producing global brain ischemia. In the management of raised ICP, all correctable factors must first of all be dealt with, then a choice made between hypnotic drugs and osmotic therapy according to whether the cause of raised ICP is, respectively, vascular or nonvascular.

Blood Volume↗

Retransplantation following isolated lung transplantation.

The results of retransplantation for early allograft failure are discouraging. Fortunately, with recent technical advances and improved postoperative immunosuppression, airway complications have been significantly reduced. It is now unusual to see patients with airway complications following lung transplantation. This group of patients is not likely to represent a large population in need of retransplantation in the future. However, rejection-mediated OB remains a persistent problem seen in all transplant centers. The group of patients who deteriorate despite augmented immunosuppression will put increasing pressure on transplant programs to provide the only known solution for survival: retransplantation. In the Toronto experience, only 1 patient survived early retransplantation. Three of the 5 recipients retransplanted late in their course have survived and 2 are presently alive and well. Yet this is in sharp contrast to the current 80% 1-year survival for initial transplant recipients. As the demand for donor lungs increases with the growing need for first-time procedures, the use of donor lungs for retransplantation becomes a significant problem. The decision whether to allocate a donor lung (and commit significant hospital resources) to a retransplant recipient or to a first-time recipient is difficult. A patient with early graft failure has a dismal prognosis and a decision not to retransplant may be straightforward. However, the decision to retransplant a patient who has developed OB late following their initial transplant is much more difficult. It is still our responsibility to manage this limited resource and provide donor lungs to those who have the optimal chance of survival.

Adolescent↗

Staging: the key to rational management of lung cancer.

Staging is the quantitative assessment of malignant disease and allows logical groupings of patients with a similar extent of disease for prognostic, therapeutic, and analytic purposes. In bronchogenic carcinoma a stage is assigned based on size, location, and the extent of invasion of the primary tumor, as well as the presence of any regional or metastatic disease. Selecting the most appropriate treatment for a patient with bronchogenic carcinoma depends on precise staging. The extent of local invasion and presence of metastatic disease will determine the likelihood of complete resection and possible cure. Careful assessment of the history, blood chemistry, radiographic studies, bronchoscopy, mediastinoscopy, and exploration (thoracotomy) are all important staging tools. Routine radionuclide scans have no useful role when there is no clinical or laboratory evidence of metastases. The T status of a tumor is best judged by bronchoscopy and at thoracotomy. Thoracic surgeons must be familiar with the techniques available to determine T status intraoperatively and use this information when planning resection. Computed tomography of the chest has fallen short in predicting direct invasion of the mediastinum and chest wall. Cervical and anterior mediastinoscopy remain important tools in determining operability. Intraoperative assessment of node involvement determines the extent of resection and likelihood of cure.

Humans↗

Bilateral lung transplantation for cystic fibrosis. The Toronto Lung Transplant Group.

Between March 1988 and March 1991, 17 patients underwent bilateral lung transplantation for end-stage lung disease caused by cystic fibrosis. There were 11 male and six female patients. Ages ranged from 19 to 41 years (mean age 28 years). Preoperative mean arterial oxygen tension with the patient breathing room air was 54 +/- 6 mm Hg; forced vital capacity, 1.8 +/- 0.7 L; forced expiratory volume in 1 second, 0.9 +/- 0.3 L; and 6-minute walk test, 506 +/- 44 m. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone. Induction immunosuppression was obtained with Minnesota antilymphocyte globulin. All patients received perioperative antibiotics according to sputum cultures and sensitivities. There were six operative deaths, four of which resulted from bacterial infection. Two patients required a second transplantation, one receiving a single lung and one undergoing bilateral lung replacement. Significant functional improvement was observed in all survivors. At 3 months follow-up, mean arterial oxygen tension on room air was 95 +/- 6 mm Hg (p less than 0.01); forced vital capacity, 3 +/- 0.8 L (p less than 0.01); forced expiratory volume in 1 second, 2.6 +/- 0.9 L (p less than 0.01); and 6-minute walk test, 678 +/- 47 m (p less than 0.01). The actuarial survival rate was 66% at 3 months and 58% at 6, 12, and 24 months. The most frequent cause of morbidity and mortality was acute pneumonia resulting from Pseudomonas cepacia. For patients with respiratory failure caused by cystic fibrosis, bilateral lung transplantation is an effective treatment option associated with significant functional improvement.

Adult↗

Pulmonary transplantation. Early and late results. The Toronto Lung Transplant Group.

Between November 1983 and March 1991, we performed 50 single and 40 double lung transplants in 82 recipients. Early deaths occurred in six (13%) single and in eight (21%) double lung transplant recipients. Late deaths occurred in 11 (28%) single and in one (3%) double lung recipients. Twenty-three of 37 (62%) single and 17 of 24 (71%) double lung transplant recipients have survived at least 1 year after the operation. In patients surviving at least 3 months after the operation (36 of 47 single lung transplant [77%] and 28 of 37 double lung transplant recipients [76%]), significant improvement occurred in arterial blood gases, pulmonary function tests, and exercise capacity. During our initial experience, airway anastomotic complications were the main cause of early morbidity and mortality. With newer surgical techniques and improved perioperative care, airway complications are now uncommon. Infectious complications, either bacterial (Pseudomonas cepacia) or viral (cytomegalovirus), are now the main cause of early mortality. Chronic rejection in the form of obliterative bronchiolitis has become a frequent cause of late morbidity.

Adult↗

Laminin-like immunoreactivity in the snail Helisoma: involvement of approximately 300 kD extracellular matrix protein in promoting outgrowth from identified neurons.

Polyclonal antibodies directed against laminin (LM), and against the A and B chains of reduced LM were used to identify antigenically related proteins in the extracellular matrix (ECM) of the snail Helisoma trivolvis. Immunofluorescence of snail central ganglionic rings using either the anti-LM or anti-B chain antibodies labeled the ECM within ganglionic sheaths as well as basal laminae surrounding the ganglia. Both the anti-LM and anti-B chain antibodies recognized a prominent, approximately 300-kD protein on immunoblots of a snail central ganglion preparation enriched in ECM components. The anti-A chain antibody failed to label any structures in sections of snail ganglia or to recognize any proteins on immunoblots of ganglionic ECM. A polyclonal antibody was raised against the approximately 300-kD snail protein. Immunofluorescence of snail ganglia with the anti- approximately 300-kD antibody gave a distribution of labeled structures comparable to that obtained with the anti-LM antibody. Immunofluorescent labeling of sections of snail muscle and salivary gland with the anti- approximately 300-kD antibody revealed a distribution of reactive protein characteristic of an ECM component. Probing immunoblots of ganglionic ECM with the anti- approximately 300-kD antibody revealed the recognition of the same approximately 300-kD protein as identified by the anti-LM antibodies. Media conditioned by Helisoma central ganglionic rings (CM) contains an unidentified neurite outgrowth promoting factor (NOPF). Immunoblots of CM probed with the anti-B chain and anti- approximately 300-kD antibodies reveal the recognition of a soluble approximately 300-kD protein similar to the approximately 300-kD protein identified in snail ECM. The ganglionic ECM preparation containing the approximately 300-kD protein supported outgrowth from cultured snail buccal neurons B5, and addition of anti- approximately 300-kD Fab fragments to CM abolished its outgrowth promoting activity. These results suggest that the approximately 300-kD ECM protein may be the NOPF in CM and/or functions in promoting neurite outgrowth.

Animals↗

Parametric imaging of cerebral vascular reserve. 2. Reproducibility, response to CO2 and correlation with middle cerebral artery velocities.

We report the reproducibility and response to change in end-tidal CO2 of a new method of quantifying regional mean cerebral transit time (MCTT) compared with the reproducibility and CO2 reactivity of middle cerebral artery (MCA) blood flow velocities measured using transcranial Doppler ultrasound. Within the range of end-tidal CO2 which could be achieved in conscious subjects breathing spontaneously, hemispheric MCTT, peak MCA velocity and mean MCA velocity showed a linear relationship with end-tidal CO2. After correction to a standardised end-tidal CO2, the coefficients of variation were 5.7% for hemispheric MCTT, 6.3% for peak MCA velocity and 6.8% for mean MCA velocity. Under the conditions of this study, MCA blood flow velocity was proportional to the reciprocal of MCTT, which in turn represents the ratio of blood flow to blood volume. Although the two methods appear to provide similar information, measurement of MCTT is quicker to perform, is less observer-dependent, provides regional information, uses conventional equipment present in most nuclear medicine departments and is less subject to problems associated with patient movement.

Adult↗

The contribution of arachidonic acid to the aetiology and pathophysiology of focal brain oedema; studies using an infusion oedema model.

Arachidonic acid solution (2 to 15 mg/ml) was infused into the right forebrain white matter of anaesthetised cats over three hours to evaluate its contribution to the genesis and pathophysiology of vasogenic brain oedema. The 0.6 ml infusion increased local white matter water content by a mean of 11.3 ml/100 g tissue but did not increase cortical water content. Histological studies revealed local expansion and trabeculation of the white matter with aggregations of granulocytic neutrophils in the venules and perivenular brain. The adjacent cortical cytoarchitecture was normal. The white matter around the infusion site was stained lightly and over a variable area (15-20 mm2) by intravenously administered Evans Blue dye 2%. Regional cerebral blood flow (rCBF) adjacent to the frontal infusion did not change significantly during the period of infusion and remained similar to rCBF in the contralateral hemisphere. Following the arachidonic acid infusion regional CBF CO2 reactivity was normal and three was no asymmetry of either cortical somatosensory evoked potential (SEP) or motor evoked potential (MEP) waveforms. The increase in brain water content and changes in the ICP and ICP related biodynamics (pressure-volume index, lumped craniospinal compliance and CSF outflow resistance) were similar to those seen following infusion of 0.6 ml saline. These studies suggest that free intraparenchymal arachidonic acid, at concentrations exceeding those occurring in most neuropathological conditions, can increase the normal brain parenchymal capillary permeability but does not disrupt focal cerebrovascular and electrophysiological function. The clinical implications of these findings are discussed.

Animals↗

Transcranial stab wounds: morbidity and medicolegal awareness.

In this series of eight patients with transcranial stab wounds, the importance of classifications of such wounds as a separate traumatic entity is stressed. The mechanisms of neuronal and vascular damage in these wounds are discussed and are found to be specific from other head injuries. Cerebral injury by stabbing is largely restricted to the wound tract. Frontal stabs (two cases) are accompanied by the least morbidity and mortality, while temporal stabs (four cases) are more commonly fatal. In transorbital stabs (two cases) carotid-cavernous fistulae resulted. Early recognition, administration of antitetanus serum and antibiotics, and debridement may minimize complications.

Adult↗

Jugular bulb cannulation: description of a cannulation technique and validation of a new continuous monitor.

We have compared in vivo oxygen saturation recordings obtained from the Oximetrix 3 with in vitro measurements using the Instrumentation Laboratories 282 Co-Oximeter. The small mean difference (0.85%) and close limits of agreement (-4% to 6%) are close enough for clinical purposes, provided in vivo calibration is performed after insertion of the fibreoptic catheter and repeated at least every 12 h. Continuous monitoring of jugular bulb oxygen saturation during intensive care of brain injured patients is now possible using fibreoptic technology. This technique may be of value in detecting global ischaemia, and as a predictor and monitor of cerebral perfusion pressure therapy.

Catheterization, Central Venous↗