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Biomedical subjects

J R Roberts

Publications and source records attributed to J R Roberts.

At least 55 records · Page 3Linked to original sources

The effects of cortisol and testosterone on renal function in male Antechinus stuartii (Marsupialia).

Seasonal changes in the physiology of Antechinus stuartii result in complete male mortality after mating. The most important endocrine changes in males are large rises in plasma testosterone and cortisol concentrations. Glomerular filtration rate (GFR) in males declines coincident with high plasma testosterone and cortisol. In the present study GFRs were measured in males captured in May (when endogenous plasma testosterone and cortisol levels are low) and given depot injections of either saline, testosterone-only, cortisol-only or testosterone plus cortisol at doses designed to mimic plasma levels during the mating period. GFR decreased significantly with testosterone injection, independent of cortisol treatment. Urinary concentrations of sodium and chloride, and osmolality decreased significantly with cortisol treatment, although the addition of testosterone reversed the effect. Total urinary excretion of electrolytes was similar between groups. Plasma potassium levels significantly increased in testosterone plus cortisol treated males. Plasma sodium levels significantly increased and plasma chloride significantly decreased in all groups treated with cortisol. Water consumption significantly increased in all cortisol-treated males and food consumption significantly increased in all testosterone-treated males. The seasonal renal functional changes observed in A. stuartii were mimicked by testosterone administration.

Animals↗

The effect of infusion of hypertonic saline on glomerular filtration rate and arginine vasotocin, prolactin and aldosterone in the domestic chicken.

Domestic fowl were infused for 60 min with isotonic saline followed by 90 min with hypertonic saline. Plasma electrolyte concentrations, osmolality and haematocrit were measured. Urine electrolyte excretion rates, osmolar output and urine flow rates were also monitored. From these results fractional excretions of electrolytes were calculated. The renal function markers inulin and rho-amino hippuric acid were infused to enable the measurement of glomerular filtration rate and plasma clearance of rho-amino hippuric acid, respectively. Plasma samples were also taken to assay for the hormones prolactin, aldosterone and arginine vasotocin. Plasma electrolytes and osmolality, fractional excretion of electrolytes and osmolar output all increased, while haematocrit decreased, throughout the experiment. However, no significant change was found in urine flow rate and little change was seen in glomerular filtration rate. The clearance of rho-amino hippuric acid, which provides an indication of renal plasma flow, increased during hypertonic saline infusion. Plasma concentrations of aldosterone and prolactin decreased during the experiment and plasma concentrations of arginine vasotocin increased. Infusion of hypertonic saline had no consistent effect on glomerular filtration rate, which may be due to conflicting influences of expansion of the extracellular fluid volume and increased plasma osmolality.

Aldosterone↗

Resection of a pulmonary malignancy invading the intrapericardial inferior vena cava.

Resection of extensive lung cancers invading thoracic vascular structures (T4 lesions) can yield long-term survival provided the margins and nodes are free of tumor. We report the resection of the suprahepatic inferior vena cava for direct tumor involvement by a pulmonary malignancy. The resection was performed without bypass, and the cava was subsequently reconstructed with a 22-mm-diameter Dacron graft. Patency was documented on postoperative magnetic resonance angiograms. The patient was discharged home on postoperative day 10 without complications and remains well 8 months after the operation. Potentially curative resections and reconstructions of suprahepatic inferior vena cava involved with pulmonary malignancies are possible and can be done without cardiopulmonary bypass.

Carcinoma, Squamous Cell↗

Comparison of open and thoracoscopic bilateral volume reduction surgery: complications analysis.

BACKGROUND: The effectiveness of lung volume reduction for the treatment of patients with emphysema is well established, but data about the surgical approach, the postoperative management, and complications are limited. We report a comparison of patients undergoing bilateral lung volume reduction (BLVRS) via median sternotomy and thoracoscopic techniques with emphasis on hospital course and complications. METHODS: All patients undergoing BLVRS at Hospital of University of Pennsylvania were analyzed for mortality and morbidity, using a combination of prospective data analysis and retrospective chart review. RESULTS: Patients undergoing BLVRS via median sternotomy were older than those undergoing video-assisted thoracoscopic surgery (VATS) procedures (63.9+/-6.89 vs 59.3+/-9.4 years, p = 0.005). Operating time was longer for the VATS procedure (147 versus 129 minutes, p = 0.006) while estimated blood less was greater for median sternotomy (209 versus 82 L, p = 0.0000017). Significant differences were found in intensive care unit stay, days intubated, life-threatening complications, respiratory complications, requirement for tracheostomy, and death that favored VATS BLVRS. When only later cohorts of patients were compared, more life-threatening complications and deaths were found in patients undergoing BLVRS by median sternotomy. There were no differences between early and late median sternotomy BLVRS patients. Twenty-six percent of the lethal complications in median sternotomy BLVRS patients were bowel perforations, equally divided between duodenal ulcers and colons. CONCLUSIONS: Managing patients after BLVRS remains complex. Bilateral video-assisted volume reduction offers equivalent functional outcome with potentially decreased morbidity and mortality. Gastrointestinal perforations can complicate the management of these patients.

Blood Loss, Surgical↗

Effect of volume reduction on lung transplant timing and selection for chronic obstructive pulmonary disease.

BACKGROUND: End-stage chronic obstructive pulmonary disease has traditionally been treated with lung transplantation. For 2 years, our lung transplantation program has placed patients with appropriate criteria for lung transplantation and volume reduction into a prospective management algorithm. These patients are offered the lung volume reduction option as a "bridge" to "extend" the eventual time to transplantation. We examine the results of this pilot program. METHODS: From October 11, 1993, to April 17, 1997, 31 patients were evaluated for lung transplantation who also had physiologic criteria for volume reduction (forced expiratory volume in 1 second < or = 25%; residual volume > 200%; significant ventilation/perfusion heterogeneity). All patients completed 6 weeks of pulmonary rehabilitation and then had baseline pulmonary function and 6-minute walk tests. These patients were then offered volume reduction as a "bridge" and were simultaneously listed for transplantation. Postoperatively, these 31 patients were then divided into two groups: Those with satisfactory results at 4 to 6 months after volume reduction and those with unsatisfactory results. Volume reduction was performed through a video thoracic approach in 87% of the patients and bilateral median sternotomy in the remaining 13%. The condition of the patients was monitored after the operation with repeated pulmonary function tests and 6-minute walk tests at 3-month intervals. RESULTS: Twenty-four of 31 patients (77.4%) had primary success (at 4 to 6 months) results after lung volume reduction and 7 patients (22.6%) had primary failure, including 1 patient who died in the perioperative period (3.2%). Four patients (16.7%) from the primary success cohort had significant deterioration in their pulmonary function during intermediate-term follow-up and were then reconsidered for lung transplantation. Two of them have subsequently undergone transplantation with good postoperative pulmonary function results. Interestingly, three patients had alpha 1-antitrypsin deficiency; two had a poor outcome of lung volume reduction and primary failure. CONCLUSIONS: Lung volume reduction in these patients is safe. Seventy-seven percent of otherwise suitable candidates for lung transplantation achieved initial good results from volume reduction and were deactivated from the list (placed on status 7). Most patients entering our prospective management algorithm have either significantly delayed or completely avoided lung transplantation after volume reduction. Lung volume reduction has substantially affected the practice, timing, and selection of patients for lung transplantation. Our waiting list now has a reduced percentage of patients with a diagnosis of chronic obstructive pulmonary disease compared with 3 years ago. Our experience suggests that lung volume reduction may be limited as a "bridge" in alpha 1-antitrypsin deficiency.

Algorithms↗

Epinephrine absorption in children with a history of anaphylaxis.

BACKGROUND: Prompt injection of epinephrine is the cornerstone of systemic anaphylaxis treatment. The rate of epinephrine absorption has not been reported previously in allergic children. OBJECTIVE: Our objective was to study the clinical pharmacology of epinephrine in this population. METHODS: We performed a prospective, randomized, blinded, parallel-group study in 17 children with a history of anaphylaxis to food, Hymenoptera venom, or other substances. We injected 0.01 ml/kg epinephrine solution (maximum 0.3 ml [0.3 mg]) subcutaneously, or 0.3 mg epinephrine intramuscularly from an autoinjector. Plasma epinephrine concentrations, heart rate, blood pressure, and adverse effects were monitored. RESULTS: In nine children who received epinephrine subcutaneously, the mean maximum plasma epinephrine concentration (+/- SEM) was 1802 +/- 214 pg/ml, achieved at a mean time of 34 +/- 14 minutes (range, 5 to 120 minutes). Only two of the nine children achieved maximum plasma concentrations by 5 minutes. In eight children who received epinephrine intramuscularly, the mean maximum plasma concentration was 2136 +/- 351 pg/ml, achieved at a mean time of 8 +/- 2 minutes, which was significantly faster than the mean time at which maximum plasma concentrations were achieved after subcutaneous epinephrine injection (p < 0.05). Six of the eight children achieved maximum plasma concentrations by 5 minutes. The terminal elimination half-life was 43 +/- 15 minutes. No serious adverse effects were noted in any child. CONCLUSIONS: In children, recommendations for subcutaneous epinephrine injection are based on anecdotal experience, and should be reevaluated in view of our finding of delayed epinephrine absorption when this route is used. This delay might have important clinical implications during an episode of systemic anaphylaxis. The intramuscular route of injection is preferable.

Absorption↗

An analysis of training activities in the use of critical care equipment within hospitals in the United Kingdom.

We investigated how training in the use of electromedical devices in adult and neonatal intensive care departments is organised, designed and delivered. Forty-one departments within two Regional Health Authorities in the United Kingdom returned a detailed questionnaire, from which several nonlinear models were developed using fuzzy logic analysis. The results clearly indicate that training in the use of equipment is a very minor activity, with less than 1% of departmental time spent on providing or receiving such training. Departments that had a higher level of expertise required less assistance from technical personnel. Critical care equipment can be utilised more fully, cost effectively and safely if a formal and regular training programme is implemented.

Adult↗

Effective long-term palliation of symptomatic, incurable metastatic medullary thyroid cancer by operative resection.

OBJECTIVE: To evaluate the short- and long-term consequences of palliative reresection of specific symptomatic lesions in patients with widely disseminated (incurable) medullary thyroid cancer (MTC). SUMMARY BACKGROUND DATA: Although reoperative neck microdissections can normalize calcitonin levels in patients with metastatic MTC confined to regional lymph nodes, there is no curative therapy for widely metastatic disease. However, these patients frequently have prolonged survival, but often with debilitating symptoms. METHODS: Between October 1981 and January 1997, 16 patients (mean age, 46 +/- 3 years; 10/16 female) underwent 21 palliative reoperations for unresectable MTC at the Johns Hopkins Hospital. All patients had significant symptom(s) or impending compromise of vital structures by a discrete lesion and had unequivocal preoperative evidence of a total disease burden that was unresectable. RESULTS: The mean interval from initial thyroidectomy to palliative surgery was 5.8 +/- 1.5 years. All patients had significant tumor burdens as evidenced by preoperative calcitonin values ranging from 900 to 222,500 pg/mL (nL < or = 17 pg/mL). The palliative operations consisted of reoperative neck dissection/mass excision (11), mediastinal mass resection (4), esophagectomy (1), liver trisegmentectomy (1), sigmoidectomy (1), bilateral simple mastectomies (1), pituitary resection (1), and subcutaneous mass excisions (1). All but two of the operative specimens contained MTC. There was no perioperative mortality. The long-term morbidity rate was limited to one recurrent laryngeal nerve injury. All patients had initial relief of the index symptom(s) after the palliative surgery, followed by a median actuarial symptom-free survival rate of 8.2 years. CONCLUSIONS: Patients with widely metastatic MTC often live for years, but many develop symptoms secondary to tumor persistence or progression. Judicious palliative, reoperative resection of discrete, symptomatic lesions can provide significant long-term relief of symptoms with minimal operative mortality and morbidity. In selected patients with metastatic MTC lesions causing significant symptoms or physical compromise, palliative reoperative resection should be considered despite the presence of widespread incurable metastatic disease.

Adult↗

Diffuse airway narrowing from carcinoma metastatic to the bronchial submucosa: identification by chest CT.

The differential diagnosis of dyspnea in patients with prior malignancy and nondiagnostic chest radiographs is broad. We report a case of breast carcinoma diffusely metastatic to the bronchial submucosa presenting as obstructive airway disease. Chest radiographs failed to suggest metastatic disease as the cause of dyspnea. CT, however, revealed the unusual finding of diffusely thickened and narrowed airways. Carcinoma confined to airway submucosa was identified using bronchial biopsy. We suggest that diffuse airway narrowing from submucosal metastasis can be demonstrated by CT and should be added to the differential diagnosis of dyspnea in cancer patients with nondiagnostic chest radiographs and evidence of airflow obstruction.

Adenocarcinoma↗

Evidence supporting a role for histidine-235 in cation binding to human 3-hydroxy-3-methyglutaryl-CoA lyase.

Histidine-235 of human 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase is the second basic residue in a conserved HXH motif. This residue is solvent accessible, readily reacting with the group specific reagent diethyl pyrocarbonate. Site-directed mutagenesis has been employed to substitute alanine or aspartate for H235. Characterization of the isolated H235A and H235D lyase mutants indicates that their tertiary structure is substantially intact. The mutant proteins, like the wild-type enzyme, are stoichiometrically modified by the affinity label, 2-butynoyl-CoA. Catalytic activity of the mutants is diminished by 15-fold and Km for HMG-CoA elevated approximately 4-fold in comparison with the values for wild-type enzyme. The function of H235 is suggested by investigation of the interaction of these enzymes with the dissociable divalent cation (e.g. Mg2+ or Mn2+) that is required for activity. ESR experiments show that wild-type enzyme forms a stable binary E*M complex. In contrast, H235A and H235D proteins do not efficiently form a binary complex. Significant interaction with cation (Mn2+) only occurs in the presence of the substrate analog, 3-hydroxyglutaryl-CoA. Similarly, when cation interaction is estimated in the presence of substrate using steady-state kinetic approaches, activator constants (Ka) and divalent cation Km values are measurable but are elevated by 15-90-fold over comparable estimates for the wild-type enzyme. The data confirm our earlier suggestion that both protein and substrate contribute ligands to HMG-CoA lyase's divalent cation activator. More specifically, the current observations suggest that H235 has an important function in cation binding.

Alanine↗

Pediatric Internet resources. Creation and growth of the PEDINFO index.

OBJECTIVE: To illustrate the growth of pediatric-related material on the Internet as demonstrated by the growth and use of an index of pediatric Internet resources. DESIGN: Descriptive analysis. METHODS: The log files of the computer systems on which the PEDINFO index was implemented were examined. File size of the index was measured, and a record of Internet hosts that connected to the server each day was produced. A proportion of Internet sites (n = 300) were examined for author reliability and practice enhancement value. RESULTS: In a period of 14 months, the file size grew from 7 kilobytes (KB) to more than 80 KB. By November 1995, usage exceeded 250 individuals per day and has since then leveled off to about 180 users per day. Analysis of the domains of the users showed a shift from equal proportion of "com" (commercially obtained Internet addresses) and "edu" (educational institution) addresses to an increase in com addresses with a stable proportion of edu addresses. One hundred twenty-seven sites contained patient or parent information, and 62 sites contained reference material. There was a wide range of author reliability ratings. CONCLUSIONS: From the growth of PEDINFO, we conclude that an increase in pediatric-related information available on the Internet is steady, much of which is patient or parent educational material. We anticipate further growth and use of the Internet in the exchange of information and cell for further education regarding its use so that pediatricians can more easily direct their patients to the most medically relevant sources.

Computer Communication Networks↗

Effects of testosterone and cortisol on the renal morphology of male Antechinus stuartii (Marsupialia).

The life cycle of the marsupial Antechinus stuartii includes postmating mortality of all males. A previous study found that renal morphology changes during the yearly cycle when endogenous concentrations of testosterone and cortisol are elevated in males. The present study determined whether administration of testosterone only, cortisol only, or testosterone plus cortisol affects renal structure in males at a time of year when endogenous hormones are low (May). Saline administration was used as the control. Gross morphometrics of the kidney did not show significant differences between groups. However, some pathological changes were observed in distal tubules and collecting ducts from cortisol-treated groups, and in the glomeruli of testosterone-treated males. Hypertrophy of the proximal tubules, distal straight tubules, and the cells of the cortical collecting duct occurred with the administration of testosterone. Distension of the distal convoluted tubules, cortical collecting ducts, and outer medullary collecting ducts occurred with the administration of cortisol, and there was some interaction with testosterone. Glomerular volumes increased with cortisol administration, although cortisol interacted with testosterone in the superficial glomeruli. Many of these changes mimicked those seen in the seasonal study, with the kidneys of the testosterone plus cortisol group closely resembling those of males in August, just prior to male mortality. The present study demonstrates that testosterone administration causes hypertrophy of renal tissue, whereas cortisol administration can cause tubular disruption in male A. stuartii.

Animals↗

Bilateral versus single lung transplantation for chronic obstructive pulmonary disease.

OBJECTIVE: Traditionally, despite ventilation/perfusion mismatch, single lung transplantation has been the mainstay for end-stage chronic obstructive pulmonary disease. We tested the hypothesis that bilateral sequential lung transplantation has better short- and intermediate-term results than single lung transplantation for chronic obstructive pulmonary disease. METHODS: One hundred twenty-six consecutive lung transplants have been performed from November 1991 to March 1996. Seventy-six have been for chronic obstructive pulmonary disease. The diagnosis of this disease includes emphysema (80.3%), alpha 1-antitrypsin deficiency (9.2%), lymphangioleiomyomatosis (7.9%), and obliterative bronchiolitis (2.6%). Twenty-nine transplants have been bilateral and 47 have been single. Mean age was 55.3 for patients having single lung transplantation and 48.8 for those having bilateral lung transplantation (p = 0.001). The distribution of the diagnoses was similar between the two groups. At 6 months, there were 29 survivors of single lung transplantation and 20 survivors of bilateral lung transplantation, with complete data for evaluation. Pulmonary function tests and 6-minute walk tests were evaluated at a mean of 15.4 and 12.8 months after transplantation, respectively. RESULTS: Sixty-day mortality was 21.3% for single lung transplantation versus only 3.45% for bilateral lung transplantation (p = 0.03). Additionally, Kaplan-Meier analysis revealed 1- and 2-year survivals of 71.1% and 63.3% for single lung transplantation versus 90% and 90% for bilateral lung transplantation, respectively. Multiple major morbidities were analyzed. Primary graft failure was significantly reduced in the bilateral group (p = 0.049). Both 6-minute walk tests and forced expiratory volume in 1 second were improved from baseline by both single and bilateral lung transplantation (p = 0.001). CONCLUSIONS: Bilateral lung transplantation improves forced expiratory volume in 1 second and 6-minute walk tests significantly over single lung transplantation (p < 0.0001). Both perioperative mortality and Kaplan-Meier survival (to 3 years) are significantly improved when bilateral rather than single lung transplantation is used for chronic obstructive pulmonary disease in our series (p < 0.05). This is probably the result of significantly reduced primary graft failure.

Aged↗

Advantage of high-surface-area charcoal for gastrointestinal decontamination in a human acetaminophen ingestion model.

OBJECTIVE: To compare the abilities of low-surface-area (LSA) vs 2 types of high-surface-area (HSA) activated charcoal given orally to adsorb acetaminophen in the gastrointestinal (GI) tract, as demonstrated by the impact of these agents on the serum levels and area under the curve (AUC) in a simulated human overdose model. METHODS: The main arm of the study was a prospective double-blind crossover trial in which 6 volunteers, serving as their own controls, ingested acetaminophen (50 mg/kg), followed randomly in 10 minutes by either powdered LSA charcoal (950 m2/g) or powdered HSA charcoal (2,000 m2/g) in a charcoal:drug ratio of 8:1. In a second arm of the study, 3 subjects additionally ingested an equal dose of a granular preparation of the HSA charcoal. Serial serum acetaminophen levels were analyzed at various intervals (30, 60, 90, 120, 180, 240, and 300 minutes postingestion), and a 5-hour AUC was calculated. The subjects also rated the charcoal preparations for palatability. RESULTS: Serum acetaminophen levels were lower at all measured times in the groups receiving both forms of the HSA charcoal vs the LSA product. With the powdered HSA charcoal, comparison serum levels were significantly lower at 120 minutes postingestion and all times thereafter (p < 0.05), reaching high significance at 4 and 5 hours (p < 0.001). The subjects receiving the granular HSA charcoal also had consistently lower serum acetaminophen levels than did those receiving the LSA product, and the difference in mean serum levels was significant at the 4- and 5-hour sample (p = 0.012). Compared with the LSA charcoal, at the 4-hour postingestion sample, serum acetaminophen levels were reduced by 44% to 85% by the powdered HSA charcoal. The total AUC for the 5-hour study period was also significantly reduced by the powdered HSA product (p = 0.005) and the granular HSA product (p = 0.043). All the subjects rated the powdered HSA charcoal to be more palatable and easier to drink than the powdered LSA charcoal. CONCLUSION: The surface area of oral activated charcoal is a major determining factor in its ability to limit acetaminophen absorption and to fulfill its adsorptive role in GI decontamination. In a human acetaminophen overdose model, 2 types of HSA charcoal, when compared with equal doses of LSA charcoal, significantly reduced serum levels and total acetaminophen absorption as measured by the AUC.

Absorption↗

Thoracoscopic management of descending necrotizing mediastinitis.

Descending necrotizing mediastinitis (DNM) is a lethal process originating from odontogenic, pharyngeal, or cervical infectious sources that descends along fascial planes into the mediastinum. Despite earlier use of antibiotics and surgical drainage, the mortality (>50%) has changed little since the first large series reported in the preantibiotic era. The surgical management remains controversial, with support ranging from cervical drainage alone to cervical drainage and routine thoracotomy. We report a case of thoracoscopic drainage and debridement of a mediastinal abscess resulting from descending necrotizing mediastinitis. The decreased morbidity of this approach compared with posterolateral thoracotomy and the improved drainage of the mediastinum compared with cervical drainage support this method as an attractive management of patients with DNM.

Abscess↗