Biomedical subjects

Jeffrey L Johnson

Publications and source records attributed to Jeffrey L Johnson.

At least 19 recordsLinked to original sources

PubMed2006

Prolonged follow-up after initial therapy with 2-chlorodeoxyadenosine in patients with indolent non-Hodgkin lymphoma: results of Cancer and Leukemia Group B Study 9153.

BACKGROUND: The objective of this study was to determine the efficacy and toxicity of 2-chlorodeoxyadenosine (2-CdA) in patients with untreated, indolent non-Hodgkin lymphoma (NHL). METHODS: For this multicenter, single-arm, Phase II study, 44 patients with treatment-naive, stage III or IV, indolent NHL (International Working Formulation subtypes A, B, and C) were enrolled. Patients received 0.14 mg/kg per day of 2-CdA as a 2-hour bolus infusion for 5 consecutive days every 28 days until maximal response or a total of 6 cycles. RESULTS: Thirty-eight patients were eligible for response evaluation. The overall response rate was 100% (95% confidence interval [95% CI], 90.8-100%), and the complete response rate was 31.6% (95% CI, 17.5-48.7%). In the intent-to-treat population, the median failure-free survival was 2.0 years (95% CI, 1.3-3.4 years), and the overall survival rate was 7.0 years (95% CI, 4.3-9.4 years). Six patients had sustained remissions that lasted a median of 8.7 years (range, from 5.9 years to > or =11 years). Although 68% of patients experienced at least 1 grade 3 or 4 event, consisting primarily of myelosuppression, severe infections were rare, with only 8 grade 3 infections. Four late malignancies (prostate adenocarcinoma, ductal carcinoma in situ, and myelodysplasia) and 4 patients with large cell transformation were reported. CONCLUSIONS: 2-CdA is an active, well-tolerated therapy for patients with untreated, indolent NHL.

Adolescent↗

PubMed2006

Normal mesenteric lymph blunts the pulmonary inflammatory response to endotoxin.

BACKGROUND: Mesenteric lymph may provide the mechanistic link between gut ischemia and acute lung injury after hemorrhagic shock (HS). Studies have focused on the toxic mediators that develop in the post-shock mesenteric lymph (PSML). However, a complementary possibility is that there is loss of protective mediators found in pre-shock normal mesenteric lymph (NML) after HS. We hypothesize that NML protects against inflammatory insults to the pulmonary endothelium and that this effect is lost in PSML. MATERIALS AND METHODS: Primary human pulmonary endothelial cells (HMVECs) were incubated with NML or PSML collected from rats subjected to HS and resuscitation and then stimulated with 20 ng/mL LPS. ICAM-1 surface expression was measured by flow cytometry. In subsequent experiments, lipoproteins were extracted from NML before incubation and LPS-induced ICAM-1 expression determined. RESULTS: Mean fluorescent intensity (MFI) of LPS-induced ICAM-1 in NML and PSML treated HMVECs were 10.1 +/- 2.3 versus 27.7 +/- 0.83, respectively (P < 0.05). This represented at 71% decrease in ICAM-1 expression by NML compared to ICAM-1 expression in LPS-induced controls (MFI: 34.6 +/- 6.9). Lipoprotein extraction from NML abolished this protective effect (MFI: 31.2 +/- 5.3 versus Control + LPS: 33.5 +/- 3.6, P > 0.05). Baseline ICAM-1 levels were not significantly different among control, NML, and PSML groups. CONCLUSION: Lipoproteins in NML contain anti-inflammatory properties that decrease ICAM-1 expression induced by LPS in pulmonary endothelium. Decreased protective lipoproteins after HS and resuscitation may contribute to the toxicity associated with PSML from the ischemic gut.

Albumins↗

PubMed2006

Decreased progression of postinjury lung dysfunction to the acute respiratory distress syndrome and multiple organ failure.

BACKGROUND: Postinjury organ dysfunction is a result of unbridled systemic hyperinflammation. According to the two-event construct, patients are resuscitated into an early vulnerable window of systemic hyperinflammation (primed) in which a second otherwise innocuous event precipitates uncontrolled hyperinflammation, leading to secondary organ damage and dysfunction (activated). Recent efforts to decrease postinjury morbidity have focused on limiting the potential of second events and systemic inflammation. We hypothesized that the collective effects of recently implemented therapeutic strategies have resulted in decreased activation of the systemic inflammatory response relative to priming in recent years. METHODS: Data were collected prospectively on trauma patients at risk for postinjury multiple organ failure (MOF). Inclusion criteria were age >15 years, trauma intensive care unit admission, Injury Severity Score >15 and survival >48 hours. Isolated head injuries and head injuries with an extracranial abbreviated injury score <2 were excluded. Daily physiologic and laboratory data were collected through surgical intensive care unit day 28, and clinical events were recorded thereafter until death or hospital discharge. Organ failure was characterized with the use of the Denver MOF Scale. Acute respiratory distress syndrome (ARDS) was defined according to the consensus definition. RESULTS: Over a 6.5-year period 897 patients were studied; 271 (31%) developed ARDS, and 226 (25%) developed MOF. Early lung dysfunction, as a measure of systemic priming, did not change over the study period. In contrast, the incidence of ARDS and MOF decreased from 43% to 25% and 33% to 12%, respectively. The incidence of early MOF decreased from 22% to 7% over the study period. CONCLUSIONS: Priming of the postinjury inflammatory response is an early event and is primarily influenced by the injury itself. Recent advances in postinjury care such as judicious blood transfusion, lung protective ventilation, treatment of adrenal insufficiency, and tight glucose control are known to attenuate systemic inflammation. Step-wise adoption of these therapies is coincident with a decrease in the destructive processes resulting in ARDS and MOF. The global effect is a decrease in activation of the systemic inflammatory response over recent years.

Adult↗

PubMed2006

Cervical spine fracture patterns mandating screening to rule out blunt cerebrovascular injury.

BACKGROUND: Aggressive screening for blunt cerebrovascular injury (BCVI) and prompt anticoagulation for documented injuries has resulted in a significant reduction in ischemic neurologic events. An association between vertebral artery injuries (VAIs) and specific cervical spine fracture patterns has been suggested; however, current screening guidelines would subject all patients with cervical spine fractures to imaging because no distinction has been made for carotid artery injuries (CAIs). We hypothesized that specific cervical spine fracture patterns that warrant screening evaluation exist, hence limiting unwarranted diagnostic imaging. METHODS: Patients undergoing screening for BCVI on the basis of injury patterns and mechanism have been prospectively followed at our regional trauma center since January 1996. RESULTS: During the study period from January 1996 to January 2005, there were 17,007 blunt trauma admissions. Twenty-three patients presented with symptoms of BCVI. Screening angiography was performed in 766 patients (4.5%), and diagnosed 258 (34%) patients with BCVI. One hundred twenty-five patients with BCVI had cervical spine fractures; 18 patients had isolated CAI; 84 had isolated VAI, and 23 had combined CAI and VAI. Eight patients with VAI had minor cervical fractures but underwent screening for other injury patterns. Fractures in the remaining patients with BCVI were 1 of 3 patterns. Subluxations in 56 (48%) patients, C1 to C3 cervical spine fractures in 42 (36%), or extension of the fracture through the foramen transversarium in 19 (16%). Cervical spine fractures were the sole indication for screening in 90% of the study population. Screening yield of all patients admitted with 1 of these 3 fracture patterns was 37%. CONCLUSIONS: Blunt cerebrovascular injury is associated with complex cervical spine fractures that include subluxation, extension into the foramen transversarium, or upper C1 to C3 fractures. Patients sustaining such cervical fractures should undergo prompt screening.

Adult↗

PubMed2006

Histopathologic characteristics, recurrence patterns, and survival of 129 patients with desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma (DM) has been associated with higher local recurrence rates than other types of cutaneous melanoma. Current controversies regarding locoregional treatment strategies warrant further investigation. METHODS: Retrospective review of a prospectively maintained melanoma database identified 129 patients with DM out of >12,500 melanoma patients referred for treatment from 1980 to 2003. Clinical and histopathologic characteristics, recurrence, and survival were analyzed. RESULTS: The median follow-up was 4.0 years. Of the 129 patients identified, 82 (63.6%) were male, and the median age was 55.2 years. American Joint Committee on Cancer staging was I, II, and III in 25.6%, 68.0%, and 6.4% of patients, respectively, and the mean tumor thickness was 4.42 mm. Overall survival was 76% at 5 years and 64% at 10 years; median survival was 13.0 years. A total of 51 patients (39.5%) experienced disease recurrence, with a median time to recurrence of 1.3 years. The first recurrence was local in 18 patients (14.0%), nodal in 18 patients (14.0%), and distant in 15 patients (11.6%), with median survivals of 6.7, 7.8, and 1.8 years, respectively. Statistically significant predictors of recurrence were a final positive margin status and stage, and predictors of overall survival were patient age and stage. CONCLUSIONS: Compared with other types of melanoma, DMs do demonstrate a tendency toward local recurrence, thus suggesting that narrower excision margins may not be appropriate in this population. Scrutiny of final surgical margins is critical to the local management of DM. In addition, the potential for regional nodal involvement must be considered at the time of diagnosis and during surveillance for disease recurrence.

Adult↗

PubMed2006

Hemoglobin-based oxygen carriers in trauma care: scientific rationale for the US multicenter prehosptial trial.

BACKGROUND: The greatest need for blood substitutes worldwide is in patients with unanticipated acute blood loss, and trauma is the most likely scenario. The blood substitutes reaching advanced clinical trials today are red blood cell (RBC) substitutes derived from hemoglobin. The hemoglobin-based oxygen carriers (HBOCs) tested currently in advanced clinical trials are polymerized hemoglobin solutions. METHODS: In the USA, the standard approach to restoring oxygen delivery for hemorrhagic shock has been crystalloid administration to expand intravascular volume, followed by stored RBCs for critical anemia. Allogeneic RBCs, however, may have adverse immunoinflammatory effects that increase the risk of postinjury multiple organ failure (MOF). Phase II in hospital clinical trials, as well as in vitro and in vivo work, suggest that resuscitation with an HBOC--in lieu of stored RBCs--attenuates the systemic inflammatory response invoked in the pathogenesis of MOF. Specifically, an HBOC has been shown to obviate stored RBC-provoked polymorphonuclear neutrophil (PMN) priming, endothelial activation, and systemic release of interleukins (IL) 6, 8, and 10. In a 2-event rodent study of shock-induced PMN-mediated acute respiratory distress syndrome (ARDS), the simulated prehospital administration of an HBOC markedly attenuated lung injury. RESULTS: Based on this background and work by others, we have initiated a US multicenter prehospital trial in which severely injured patients with major blood loss [systolic blood pressure (SBP) 500 injured patients have been enrolled in this multicenter trial, and the final interim analyses support the original target of 720.

Blood Substitutes↗

PubMed2006

One hundred percent fascial approximation with sequential abdominal closure of the open abdomen.

BACKGROUND: Damage-control surgery and the recognition of the abdominal compartment syndrome have improved patient outcomes but at the cost of an open abdomen. Multiple techniques have been introduced to obtain fascial closure for the open abdomen to minimize morbidity and cost of care. We performed a modification of the vacuum-assisted closure (VAC) technique that provided constant fascial tension, hypothesizing this would result in a higher rate of primary fascial closure. METHODS: After initial temporary closure of the abdomen after post-injury damage control or decompressive laparotomy for abdominal compartment syndrome, we began the sequential closure technique. The technique begins by covering the bowel with the multiple white sponges overlapped like patchwork, and the fascia is placed under moderate tension over the white sponges with #1-PDS sutures. Large black VAC sponges are placed on top of the white sponges and affixed with an occlusive dressing and standard suction tubing is placed. Patients are returned to the operating room for sequential fascial closure and replacement of the sponge sandwich every 2 days, with a resulting decrease in the fascial defect. RESULTS: Fourteen patients underwent sequential abdominal closure during the study period: 9 owing to damage control surgery and 5 owing to secondary abdominal compartment syndrome. Average time to closure was 7.5 +/- 1.0 days (range 4-16) and average number of laparotomies to closure was 4.6 +/- 0.5 (range 3-8). All patients attained primary fascial closure. CONCLUSION: We propose a modification of the previously described vacuum-assisted closure technique that achieves 100% fascial approximation in our limited experience. Further application and refinement of this technique may eliminate the need for delayed complex and costly reconstructive abdominal wall procedures for the open abdomen.

Abdominal Injuries↗

PubMed2006

Streptococcus milleri infections of the pleural space: operative management predominates.

BACKGROUND: Management of patients with thoracic empyema ranges from tube thoracostomy drainage, with or without fibrinolytics, to operative intervention, with the optimal intervention remaining uncertain. Streptococcus milleri, typically a benign bacterium colonizing the oropharynx, has recently been reported as a potential pathogen in pneumonia and pleural space disease. Our initial experience indicated this infection, when in the pleural space, was particularly tenacious and often required major operative intervention to eradicate. Therefore, we hypothesized that patients with S milleri pleural space infections often require operative intervention as definitive treatment. METHODS: We reviewed all patients from June 17, 1999 to April 15, 2005 with S milleri infections at our level I academic trauma/acute care surgery department at a safety-net hospital. S milleri infections were diagnosed by thoracentesis, bronchoalveolar lavage, tube thoracostomy fluid, or intraoperative culture. RESULTS: Over the 70-month period evaluated, of 697 patients with S milleri infections, 39 patients had S milleri infections of the pleural space; 26 (67%) patients underwent operative intervention. The majority (72%) were men with a mean age of 46 (range 22 to 63); the underlying etiology in those patients requiring operation was pneumonia (26 patients; 67%), trauma (9 patients; 23%), postoperative infection (2 patients), foreign body ingestion (1 patient), and malignancy (1 patient). The vast majority of patients in the operative group were treated preoperatively with tube thoracostomy (88%) and antibiotics (96%). The average duration of chest tube drainage prior to operation was 4.4 days (95% confidence interval [CI] 2.6 to 6.2) and antibiotic treatment was 6.0 days (95% CI 3.8 to 8.2). Thirteen patients (50%) underwent video-assisted thoracoscopic surgery (VATS) and 13 patients required thoracotomy. VATS was performed more often when operative intervention occurred early (average hospital day 6.2) compared to initial thoracotomy or conversion from VATS to thoracotomy (average hospital day 9.8). Hospital length of stay was less in the operative group (average 24 days; 95% CI 17 to 31) than in the nonoperative group (34 days; 95% CI 19 to 49), discharge to home was greater in the operative group (77% vs. 16%), and mortality was less in operative group (0% vs. 23%). CONCLUSIONS: Despite attempts at nonoperative management, the majority of patients with a S milleri pleural space infection require operative intervention for definitive therapy. Patients diagnosed with S milleri empyema should be considered for early operative intervention due to the unrelenting nature of their infection. Operative treatment is associated with a shorter hospital length of stay, increased discharge to home, and decreased mortality.

Adult↗

PubMed2006

Emergency department resuscitative thoracotomy for nontorso injuries.

BACKGROUND: Resuscitative thoracotomy performed in the emergency department (EDT) continues to have clear indications in patients sustaining trauma to the torso, particularly penetrating injuries. However, adjunctive use of aortic cross-clamping during EDT for hemorrhagic shock also may be useful in the acute resuscitation of patient with nontorso injuries (NTI). We questioned the utility of EDT in patients with nontorso trauma. METHODS: Patients undergoing EDT have been prospectively followed since 1977 at our regional level I trauma center. RESULTS: During the 26-year study period, 959 patients underwent EDT; 27 (3%) of these patients underwent EDT for penetrating NTI. Three (11%) of these patients survived to leave the hospital, with only 1 patient sustaining mild neurologic deficit. The mechanism of injury in the survivors was stab wound to the neck (1), gunshot wound to the neck (1), and extremity vascular injury (1). All survivors of EDT for NTI underwent prehospital cardiopulmonary resuscitation and successful endotracheal intubation in the field. There were no survivors of EDT for penetrating injury to the head. CONCLUSIONS: Resuscitative EDT with aortic cross-clamping is a potential adjunct in the acute resuscitation of NTI involving penetrating neck or extremity vascular injuries.

Colorado↗

PubMed2006

Sequential doxorubicin and topotecan in relapsed/refractory aggressive non-Hodgkin's lymphoma: results of CALGB 59906.

Topoisomerase enzymes are critical components of genomic replication and function to minimize torsional stress on DNA. Sequential administration of a topoisomerase II inhibitor followed by a topoisomerase I inhibitor is potentially synergistic due to increased target enzyme levels. Patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL) were eligible for this phase II study of doxorubicin 25 mg/m2 intravenous (IV) on day 1 and topotecan 1.75 mg/m2/day IV on days 3 - 5, every 21 days. The trial objectives included the overall response rate, progression-free survival, and toxicity. Twenty-six patients were enrolled and 25 patients are assessable for toxicity and response. The median age was 58 (range 23 - 74) years. The patients had received a median of two (range one to five) prior regimens, including five patients with a prior stem cell transplant. Five patients (20%, 95% confidence interval 0.07, 0.42) responded with two (8%) complete remissions and three (12%) partial remissions; an additional four (16%) patients had stable disease. Both patients achieving a complete remission had Burkitt's lymphoma. There were no treatment-related deaths. In conclusion, the combination of doxorubicin and topotecan is well tolerated and has modest activity in relapsed/refractory NHL, with occasional patients having a prolonged remission. The activity in Burkitt's lymphoma should be investigated further.

Adult↗

PubMed2006

The role of the surgeon as intensivist: an international perspective.

PURPOSE OF REVIEW: Critical care is a young specialty. It emerged less than 50 years ago in response to new technologies that could prolong the survival of patients who previously would have died. The diseases that posed this threat to life were varied and the original practitioners of critical care came from a variety of medical backgrounds, and created a multidisciplinary specialty. As it continues to evolve, however, the participation and influence of surgeons is waning. CONTENT: We have sought the perspectives of an international group of intensivists on the role of surgeons in the future of critical care. These perspectives are varied. Surgeons play the largest role in North American critical care, although even here that role is diminishing, and new models of practice are needed. Surgical involvement is even less in Japan, Europe, and South America. The important role of the surgical perspective in differentiating heroic from futile intervention is underlined by Alsanea from Saudi Arabia. CONCLUSIONS: Surgical involvement in the practice of critical care is declining around the world. The reasons are complex, and include competing clinical imperatives, economics, and the demands of training programs. New models are needed to revitalize critical care as a multidisciplinary specialty.

Argentina↗

PubMed2006

Minor depression and physical outcome trajectories in heart failure and pulmonary disease.

We examined conjoint trajectories of depression-physical illness outcomes in elderly inpatients with minor depression and heart failure or pulmonary disease, and identified demographic, psychosocial, physical, and treatment predictors of trajectory. Consecutively admitted patients over age 50 with heart failure and/or chronic pulmonary disease were screened for minor depression using the Structured Clinical Interview for Depression. Follow-up evaluations were performed at 6 and 12 weeks using the Longitudinal Interview Follow-Up Evaluation, Hamilton Depression Scale, and Chronic Heart Failure-Chronic Respiratory Disease Questionnaire. Patients were placed into four depression-physical illness outcome trajectories: (T#1) depression better, illness better; (T#2) depression better, illness same; (T#3) depression same, illness better; and (T#4) depression same, illness same. Bivariate and multivariate predictors were examined. Minor depression was identified in 587 patients. Of these, 487 were evaluated at 6 weeks and 444 at 12 weeks. By 6 weeks, 39.4% of patients improved both on depression and physical illness (T#1), and 27.3% improved on neither (T#4). By 12 weeks, 49.6% had improved on both and 20.5% on neither. Race, admitting hospital, past psychiatric history, family psychiatric history, comorbid physical illnesses, and antidepressant drug treatment independently predicted outcome trajectory. Improvements in depression and physical illness track closely together in elderly inpatients with heart failure or pulmonary disease. Baseline patient characteristics predict which outcome trajectory they are likely to follow after hospital discharge, and may be useful in diagnosis and management.

Aged↗

PubMed2006

Major depression and physical illness trajectories in heart failure and pulmonary disease.

The purpose of this study was to examine conjoint trajectories of depression-physical illness in elderly medical inpatients with heart failure and/or chronic pulmonary disease and major depression (MDD), and to identify baseline predictors of trajectory. Consecutive medically hospitalized patients over age 50 with heart failure and/or chronic pulmonary disease were screened for MDD using the Structured Clinical Interview for Depression. Patients were re-evaluated at 6, 12, 18, and 24 weeks. Four depression-physical illness conjoint trajectories were examined: depression better, illness better; depression better, illness same; depression same, illness better; and depression same, illness same. Baseline predictors of trajectory were examined. MDD was identified in 413 patients; 352 had at least one follow-up. By 6 weeks, 22.3% improved on both depression and illness and 38.1% improved on neither. By 24 weeks, 45.0% had improved on both and 24.8% on neither. Short-term baseline predictors of trajectory (6 weeks) differed from long-term (12-24 weeks); past psychiatric history, overall medical illness severity, and education were short-term predictors, whereas past psychiatric history, depression treatments, and physical functioning were long-term. Improvements in MDD and physical illness track closely together. Characteristics during baseline hospitalization predict outcome trajectory after discharge, and may be useful in understanding etiology and directing treatment.

Adaptation, Psychological↗

PubMed2006

Melanoma of the ear: treatment and survival probabilities based on 199 patients.

BACKGROUND: In 2005, it is now estimated that one in 62 Americans have a lifetime risk of developing invasive melanoma. Melanoma of the ear accounts for 1% of all cases of melanoma and 14.5% of all head and neck melanomas. With this increase in incidence, plastic surgeons will likely have to treat and manage more of these patients in the future. METHODS: A retrospective chart review was performed on 199 patients diagnosed with primary melanoma of the ear. Specimens were reviewed by same center dermatopathologists (Duke University Medical Center, Durham, NC) for standardization of histologic criteria in all but 10 patients. Surgical treatment and outcomes were reviewed and survival rates based on thickness and stage were calculated. Metastases information, anatomic location on the ear, and histologic subtype were recorded and analyzed. RESULTS: The median length of follow up was 3.3 years with a range of 0.4 to 24.9 years. Eighty-six patients were known to be dead at the last known follow-up date. The median survival time among these patients was 7.9 years. The most common histologic classification of the lesions were superficial spreading type (45.2%) and were most likely to be localized to the anterior helix (49.3%). One hundred sixty-one of 199 (80.9%) patients underwent wide local excision with local recurrence rate of 10.6%. Overall, 43.2% of patients developed a local recurrence or metastatic spread. Ulceration, thickness, and stage all negatively affected survival. CONCLUSIONS: This is the largest review of primary ear melanoma cases reported to date. Survival probabilities at 2, 5, and 10 years for melanoma of the ear based on thickness and stage are presented. Ulceration adversely affected survival probability (P < 0.003). Lesion excision with confirmed negative margins on permanent section pathology should be the goal of initial surgical therapy, and there is no apparent role for elective lymph node dissection in treatment of melanoma of the ear.

Adolescent↗

PubMed2006