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Biomedical subjects

J McDonald

Publications and source records attributed to J McDonald.

At least 109 records · Page 6Linked to original sources

Three dimensional planning target volumes: a model and a software tool.

PURPOSE: Three dimensional (3D) target volumes are an essential component of conformal therapy because the goal is to shape the treatment volume to the target volume. The planning target volume (PTV) is defined by ICRU 50 as the clinical target volume (CTV) plus a margin to ensure that the CTV receives the prescribed dose. The margin must include all interfractional and intrafractional treatment variations. This paper describes a software tool that automatically generates 3D PTVs from CTVs for lung cancers and immobile head and neck cancers. METHODS AND MATERIALS: Values for the interfractional and intrafractional treatment variations were determined by a literature review and by targeted interviews with physicians. The software tool is written in Common LISP and conforms to the specifications for shareable software of the Radiotherapy Treatment Planning Tools Collaborative Working Group. RESULTS: The tool is a rule-based expert system in which the inputs are the CTV contours, critical structure contours, and qualitative information about the specific patient. The output is PTV contours, which are a cylindrical expansion of the CTV. A model for creating PTVs from CTVs is embedded in the tool. The interfractional variation of setup uncertainty and the intrafractional variations of movement of the CTV (e.g., respiration) and patient motion are included in the model. Measured data for the component variations is consistent with modeling the components as independent samples from 3D Gaussian distributions. The components are combined using multivariate normal statistics to yield the cylindrical expansion factors. Rules are used to represent the values of the components for certain patient conditions (e.g., setup uncertainty for a head and neck patient immobilized in a mask). The tool uses a rule interpreter to combine qualitative information about a specific patient with rules representing the value of the components and to enter the appropriate component values for that patient into the cylindrical expansion formula. CONCLUSION: The portable software tool allows the rapid, consistent, and automatic generation of 3D PTVs from CTVs.

Head and Neck Neoplasms↗

Management of parapneumonic effusions. An analysis of physician practice patterns.

OBJECTIVE: To evaluate physician practices in managing patients with parapneumonic effusions and the impact of practice patterns on clinical outcome. DESIGN: Case series. SETTING: Private, tertiary care medical center. PATIENTS: Thirty-nine hospitalized patients with complicated parapneumonic effusions and a separate group of 191 patients admitted with community-acquired pneumonia. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Evaluation of physician practice patterns in managing complicated parapneumonic effusion and the impact of delaying thoracentesis (> or = 2 days after pleural fluid detection) or pleural drainage (> or = 2 days after pleural fluid criteria for drainage fulfilled) on duration of hospitalization, cost of hospitalization, and need for thoracotomy. RESULTS: Thirty-eight of the 39 patients with complicated parapneumonic effusions underwent thoracentesis that was "delayed" (5.7 +/- 3.1 days) in 16 patients. Delays in thoracentesis were associated with longer hospitalizations (P = .02). Laboratory tests ordered on nonpurulent pleural fluid were incomplete for 16 of 38 patients. Chest tube or surgical pleural drainage was delayed (4.2 +/- 3.5 days) in 10 of 38 patients who underwent thoracentesis. Delays in initiating drainage were associated with prolonged hospitalization (P = .04). Delaying interventions accounted for a mean cost increment per patient of $8462 for delayed thoracentesis and $9332 for delayed drainage. Of the 191 patients with community-acquired pneumonia, 99 (52%) had pleural effusions but only 15 (15%) underwent thoracentesis. CONCLUSIONS: Physicians commonly delay thoracentesis and chest tube drainage to observe parapneumonic effusions for improvement. This practice pattern is associated with longer and more costly hospitalizations.

Adult↗

Modifying role of trace elements on the mutagenicity of benzo[a]pyrene.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon that is found in tobacco smoke and various environmental contaminants and has been shown to be carcinogenic and mutagenic in animal and cell culture studies, respectively. Research studies suggest that various nutritional factors such as the antioxidant vitamins and selenium are very promising as potential anticarcinogenic agents. Moreover, some evidence exists showing that both iron and germanium, at specific dosage levels, may possess antimutagenic potential. This study examined the influence of ferrous sulfate and germanium oxide, independently, upon the mutagenic potential of BaP in the Ames test. Four test strains of Salmonella typhimurium were exposed to BaP (15 micrograms/plate) in the presence of different dosage levels of iron (0-1000 micrograms/plate) and germanium (0-600 micrograms/plate). In the case of iron, it was observed that, depending upon the strain tested, iron reduced BaP's mutagenicity. In strain TA98, this was a significant effect at 100 micrograms/plate and higher. In strains TA97a and TA100, iron concentrations had to reach 250 micrograms/plate or higher to produce significant effects. Iron was much less effective in reducing BaP mutagenicity in strain TA102. In general, germanium was not as effective in reducing the mutagenic potential of BaP. Only in the case of the highest concentrations tested (400 and 600 micrograms/plate) was any effect noted, and this in only three of the four strains evaluated.

Benzopyrenes↗

Recurrent pneumothoraces in ventilated patients despite ipsilateral chest tubes.

The incidence of recurrent pneumothoraces was analyzed in mechanically ventilated patients with the adult respiratory distress syndrome (ARDS) or non-ARDS causes of respiratory failure who had ipsilateral chest tubes in place. The radiographs of 39 consecutive patients with 47 initial pneumothoraces were evaluated for pneumothorax recurrence and chest tube positioning, which was prospectively defined as having a "vertical" or "horizontal" orientation. "Horizontal" positioning indicated that the chest tube may have been placed into a major fissure or the posterior hemithorax. Sixteen of the 47 pneumothoraces in all study patients, 14 of the 21 pneumothoraces in patients with ARDS, and 2 of the 26 pneumothoraces in patients without ARDS recurred (p < 0.0001) despite an ipsilateral chest tube; 9 of the 14 ARDS pneumothorax recurrences were tension types. "Horizontal" chest tube positioning in patients with ARDS had a positive predictive value of 86% and 64% for recurrences of pneumothoraces and tension pneumothoraces, respectively. Recurrent pneumothoraces occur commonly in mechanically ventilated patients with ARDS despite ipsilateral chest tubes. Because pneumothorax recurrences appear to be related to horizontal chest tube placement, imaging studies should verify that chest tubes are placed in optimally in the anterior hemithorax away from interlobar fissures in this patient population.

Adult↗

Phosphorylation and activity of Na+/H+ exchanger isoform 1 of immortalized lymphoblasts in diabetic nephropathy.

In both essential hypertension and diabetic nephropathy (DN), the ubiquitous cellular Na+/H+ exchanger (NHE) exhibits altered kinetics with increased transport activity. The mechanism for this phenotype and its dependence on the presence of serum are unknown, but increased lymphoblast NHE activity in DN has been attributed to a defect in post-translational processing of NHE-1 rather than an increased cellular exchanger number. Phosphorylation of NHE-1 has been proposed to play a role in its activation in a variety of cell models. We have examined, therefore, the role of NHE-1 phosphorylation and the effect of serum in determining the increased NHE-1 activity in lymphoblasts from patients with DN. Cells from these patients exhibited increased NHE activity in the presence and absence of fetal calf serum (range 42-59%, P < 0.005, analysis of variance) and an increased proliferation rate (P < 0.01) when compared with cells from both normoalbuminuric diabetic patients and non-diabetic control subjects. However, NHE-1 abundance was very similar among all groups in the presence and absence of serum, indicating that increased NHE activity in cells of nephropathy patients was due to an increased turnover number. This nephropathy phenotype was not accompanied by an increased net phosphorylation of NHE-1 in the presence or absence of serum. Our findings suggest that increased NHE-1 activity in cells of DN patients is independent of the presence of serum and is not attributable to altered NHE-1 phosphorylation. Additional post-translational mechanisms for activation of NHE-1, therefore, may be involved.

Adult↗

Treatment of porcine cysticercosis with albendazole.

In a randomized, controlled study, the efficacy and safety of two different schemes of albendazole therapy for treatment of porcine cysticercosis were tested. Seventeen naturally infected pigs were divided into three groups and treated per os with albendazole (50 mg/kg single dose), albendazole (30 mg/kg every day for three days), or given no treatment, respectively. Serologic responses were monitored with the enzyme-linked electroimmunotransfer blot assay. Pigs were humanely killed 12 weeks after treatment, necropsied, and the number of parasites was recorded. Scolex evagination was used to assess viability of the cysts. Both albendazole-treated groups had significant side effects (anorexia, lethargy). Only a single viable cyst was recovered from the brain of one animal after therapy in the multiple-dose group, and the single-dose therapy left 11% of the cysts viable. In contrast, more than 90% of muscle cysts were found to be viable in the untreated group. Although albendazole therapy for three days was found to be highly effective, side effects and the need for multiple doses would still prevent its widespread use.

Albendazole↗

Liver transplantation. When is it indicated and what can be expected afterwards?

Orthotopic liver transplantation is an established form of therapy for selected patients who have chronic parenchymal liver disease with cirrhosis, a chronic cholestatic syndrome, fulminant hepatic failure, or unresectable hepatic malignant disease. In most centers with experienced staff, 5-year survival rates exceed 70%. For a good outcome, it is essential that the patient be referred to a transplant center early, before overt clinical deterioration occurs. Following transplantation, lifelong immunosuppression is required to prevent allograft rejection, and extensive follow-up is necessary for early reversal of complications. The primary care physician plays a critical role in identifying organ donors.

Humans↗

Alosetron does not affect the visceral perception of gastric distension in healthy subjects.

BACKGROUND: The effect of alosetron, a new specific 5-HT3 receptor antagonist, on the visceral perception in response to gastric distension was assessed in 12 healthy male subjects in a randomized, double-blind, placebo controlled crossover trial. METHODS: Each subject was given orally either alosetron 1 mg b.d. or placebo b.d. for 6 days (wash-out period 7-28 days). At the end of each dosing period, both isobarometric and isovolumetric gastric distensions were performed using an electronic barostat. RESULTS: Alosetron did not modify the gastric wall compliance (pressure-volume relationship). Alosetron had an effect similar to placebo on the visceral perception scores in both isobarometric and isovolumetric distensions. The mean (+/- SEM) thresholds for abdominal discomfort were, respectively, 16.8 +/- 0.7 mmHg and 825 +/- 61 mL with alosetron, 16.7 +/- 0.6 mmHg and 883 +/- 45 mL with Placebo (P = NS). CONCLUSIONS: 5-HT3 receptors do not appear to be involved in the visceral perception of gastric distension in healthy subjects.

Administration, Oral↗

Relationship between neuropeptide Y and luteinizing-hormone-releasing hormone immunoreactivities in the hypothalamus and preoptic region.

The purpose of this study was to examine the anatomical relationships of perikarya and fibers containing neuropeptide Y (NPY) and luteinizing-hormone-releasing hormone (LHRH) in the hypothalamus and preoptic region of female rats. In view of our previous report of stimulatory effects of estrogen on LHRH and NPY levels in the median eminence, animals were bilaterally ovariectomized and subsequently implanted subcutaneously with capsules containing estradiol benzoate in oil or vehicle. Following intracerebroventricular injection of colchicine, rats were perfused with fixative and their brains sectioned and processed for immunohistochemical visualization of NPY and LHRH in the same section and in consecutive sections. Estrogen treatment had no discernible effect on the distribution or relationship of these peptides. NPY-immunoreactive fibers were intimately associated with LHRH-labeled primary dendrites and perikarya in the medial preoptic region and horizontal limb of the diagonal band of Broca. Fibers containing NPY or LHRH overlapped extensively in the lateral palisade region of the median eminence and also in the subependymal and internal zones. The external zone of the median eminence displayed relatively less overlap of these peptide systems. LHRH-immunoreactive axons coursed among NPY-labeled perikarya in the arcuate nucleus and appeared to contact these cells. These results suggest that NPY-containing axons may influence LHRH-positive neurons at the cell body and also at the site of axon termination in the median eminence. LHRH-containing axons appear to contact NPY-immunoreactive perikarya in the arcuate nucleus and may interact with terminals in the median eminence. This arrangement may provide a mechanism for communication between NPY and LHRH neurons and for the neuroendocrine coordination of hypothalamic NPY and LHRH secretion before ovulation.

Animals↗

Use of sentinel pigs to monitor environmental Taenia solium contamination. The Cysticercosis Working Group in Peru (CWG).

We tested a novel approach to assay Taenia solium prevalence using the enzyme-linked immunoelectrotransfer blot assay in sentinel piglets to determine environmental contamination with T. solium eggs in a disease-endemic zone in Peru. Twelve sentinel piglets from an area where the disease is not present were tested at two months of age, moved to an area where the disease is endemic, and retested at the of age nine months. Sentinel piglets native from this T. solium-endemic area were also tested concurrently at two and nine months of age. Of the non-native pigs, 33% (4 of 12) acquired new infection. Of the 28 native pigs tested, 64% (18 of 28) acquired the infection. In a subset of the native piglets from seronegative sows, 44% (4 of 9) were infected at five months of age. Serodiagnosis of sentinel piglets is a practical method to detect T. solium eggs in the environment. Furthermore, it permits indirect assessment of human risk, which may be useful for monitoring the efficacy of intervention programs.

Animals↗

The feasibility and efficacy of early discharge planning initiated by the admitting department in two acute care hospitals.

To determine the feasibility and efficacy of early discharge planning, initiated by admitting department personnel, a randomized, controlled trial was undertaken in 2 acute care, university-affiliated hospitals. The intervention tested was referral of patients by admitting personnel to nursing, social work, physiotherapy, occupational therapy, or dietary services for potential discharge planning. A 1-page, 65-item questionnaire was designed to identify patients for referral to the various allied health services. A copy of this was sent to the appropriate service, according to predefined criteria. The questionnaire took an average of 4 min to complete. The criteria used were highly predictive of length of stay, the most important being age, followed by living outside St. John's, admission within the previous 3 months, emergency admission, and being in need of community services. In Hospital A, the cases (n = 421) referred for early discharge planning had significantly shorter length of stay (Mantel-Cox, p = 0.03) than controls (n = 420), who were identical for all factors predictive of prolonged length of stay. The reduction in length of stay amounted to a mean of 0.8 d. In Hospital B (n = 758), the intervention was less effective because of a lower proportion of patients with factors associated with prolonged hospital stay and, perhaps, because of inadequate implementation of the program. We conclude that identification, by admitting department personnel, of patients who may benefit from early discharge planning is feasible. This process will reduce length of hospital stay, but its effectiveness is dependent on case mix variables and enthusiastic implementation of the program.

Acute Disease↗