Biomedical subjects
Publications and source records attributed to W Wheeler.
Three methods of nucleotide character analysis are discussed. Their implications for molecular sequence homology and phylogenetic analysis are compared. The criterion of inter-data set congruence, both character based and topological, are applied to two data sets to elucidate and potentially discriminate among these parsimony-based ideas.
Multiple sequence alignment is discussed in light of homology assessments in phylogenetic research. Pairwise and multiple alignment methods are reviewed as exact and heuristic procedures. Since the object of alignment is to create the most efficient statement of initial homology, methods that minimize nonhomology are to be favored. Therefore, among all possible alignments, the one that satisfies the phylogenetic optimality criterion the best should be considered the best alignment. Since all homology statements are subject to testing and explanation this way, consistency of optimality criteria is desirable. This consistency is based on the treatment of alignment gaps as character information and the consistent use of a cost function (e.g., insertion-deletion, transversion, and transition) through analysis from alignment to phylogeny reconstruction. Cost functions are not subject to testing via inspection; hence the assumptions they make should be examined by varying the assumed values in a sensitivity analysis context to test for the robustness of results. Agreement among data may be used to choose an optimal solution set from all of those examined through parameter variation. This idea of consistency between assumption and analysis through alignment and cladogram reconstruction is not limited to parsimony analysis and could and should be applied to other forms of analysis such as maximum likelihood.
Issues concerning transformational and taxic comparisons are central to understanding the impact of the recent proliferation of molecular developmental data on evolutionary biology. More importantly, an understanding of taxism and transformationalism in comparative biology is critical to assessing the impact of the recent developmental data on systematic theory and practice. We examine the philosophical and practical aspects of the transformational approach and the relevance of this approach to recent molecular-based developmental data. We also examine the theoretical basis of the taxic approach to molecular developmental data and suggest that developmental data are perfectly amenable to the taxic approach. Two recent examples from the molecular developmental biology literature--the evolution of insect wings and the evolution of dorsal ventral inversion in vertebrates and invertebrates--are used to compare the taxic and transformational approaches. We conclude that the transformational approach is entirely appropriate for ontogenetic studies and furthermore can serve as an excellent source of hypotheses about the evolution of characters. However, the taxic approach is the ultimate arbiter of these hypotheses.
This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death.
The description of sphero-cylinder lenses is approached from the viewpoint of Fourier analysis of the power profile. It is shown that the familiar sine-squared law leads naturally to a Fourier series representation with exactly three Fourier coefficients, representing the natural parameters of a thin lens. The constant term corresponds to the mean spherical equivalent (MSE) power, whereas the amplitude and phase of the harmonic correspond to the power and axis of a Jackson cross-cylinder (JCC) lens, respectively. Expressing the Fourier series in rectangular form leads to the representation of an arbitrary sphero-cylinder lens as the sum of a spherical lens and two cross-cylinders, one at axis 0 degree and the other at axis 45 degrees. The power of these three component lenses may be interpreted as (x,y,z) coordinates of a vector representation of the power profile. Advantages of this power vector representation of a sphero-cylinder lens for numerical and graphical analysis of optometric data are described for problems involving lens combinations, comparison of different lenses, and the statistical distribution of refractive errors.
We retrospectively studied the relation between corticasteroid therapy, hypogammaglobulinemia (HG), and recurrent infections in 37 infants with moderate to severe bronchopulmonary dysplasia (BPD). Nineteen of the 37 patients had tracheostomies because of chronic respiratory failure. We hypothesized that recurrent infections were most prevalent in infants whose IgG levels remained low at one year of age (persistent HG) and in infants receiving high doses of corticosteroids during the first year of life. We further hypothesized that the duration of HG was strongly correlated with the cumulative first year steroid dose. We also studied the response to intravenous gammaglobulin (IVIG) replacement therapy in this population of BPD infants. Our results showed an association between first year corticosteroid dose, duration of HG (r = 0.49, p < 0.003), and frequency of infections (r = 0.51, p < 0.001). We noted a relatively strong correlation between frequency of infections and duration of HG (r = 0.84, p < 0.0001). Twenty-four of 37 (65%) infants showed persistent HG and 49% had evidence of abnormal specific antibody production. Sixty-four percent of infants studied had reduced lymphocyte responsiveness to mitogen stimulation. Nineteen of 37 (51%) infants required IVIG for an average duration of 17.9 months due to recurrent infections. The average number of infections per year decreased from 10.6 to 2.8 (t = 12.32, p < 0.0001). There were no complications associated with IVIG therapy, but one infant died of bronchiolitis obliterans following heart-lung transplantation. Eight of 37 (22%) infants have persistent immunologic dysfunction requiring ongoing IVIG at four years or more of follow-up. We conclude that a substantial number of ill infants with BPD will have immune dysfunction characterized by persistently low IgG levels and reduced specific antibody responsiveness to protein antigens. We speculate that these findings are related to the cumulative dose of corticosteroids received in the first year of life and to the severity of underlying disease.
Forty-seven preterm infants, who were previously enrolled in a prospective, randomized, blinded study at birth to assess the effects of multiple doses of exogenous bovine surfactant to prevent respiratory distress syndrome, underwent lung function evaluation and review of their medical histories at 2 1/2 years of age. During their initial hospitalization there were no differences between the 17 control infants and the 30 surfactant-treated infants in the duration of ventilator or oxygen therapy and the incidence of bronchopulmonary dysplasia. At the follow-up both groups were similar in chronological and corrected ages, weights, lengths, and sex ratios and there were no differences in the occurrence of allergy, asthma, bronchiolitis, eczema, pneumonia, and wheezing. In addition, there was no significant difference regarding the incidence of chest illnesses lasting either 3 or 7 days and in the total number of required rehospitalizations. Functional residual capacity (FRC), tidal volume (VT/kg), compliance (Crs/kg), resistance (Rrs), and time constant of the respiratory system were not significantly different between the two groups at 2 1/2 years of age. We conclude that bovine surfactant, when given during the neonatal period, has little long-term effect on lung function. Neonatal bovine surfactant therapy neither improves nor produces any adverse effects on the developing respiratory system.
Molecular systematists generally rely on computer algorithms to establish the alignment of DNA sequences. However, when alignment regions are characterized by multiple insertions and deletions, these gap-filled stretches of DNA are often excised before phylogenetic reconstruction. This exclusion of systematic data is generally determined by subjective criteria. We explore a replicable methodology in which the comparison of several multiple sequence alignments can be used to eliminate regions of unstable sequence alignment. Using crocodilian and insect mitochondrial (mt) ribosomal (r) DNA as examples, we caution against the removal of sequence data prior to phylogenetic reconstruction.
We report here a patient who presented with locally advanced Jackson Stage IV penile squamous cell carcinoma who was managed with preoperative 5-fluorouracil, mitomycin C chemotherapy, and concurrent radiation therapy. He experienced an excellent partial response which allowed more limited surgery than would otherwise be indicated. He is still alive and well 5 years after completion of his treatment without side effects, local recurrence, or distant metastatic disease.
DNA was extracted from the fossil termite Mastotermes electrodominicus preserved in Oligo-Miocene amber (25 million to 30 million years old). Fragments of mitochondrial [16S ribosomal DNA (rDNA)] and nuclear (18S rDNA) genes were amplified by polymerase chain reaction. Phylogenetic analysis of fossil and extant 18S rDNA confirmed morphological cladistic analyses of living dictyopterans (termites, cockroaches, and mantids). The fossil termite shares several sequence attributes with Mastotermes darwiniensis. Addition of this fossil to living-species phylogeny is required to substantiate Mastotermes monophyly and affects molecular phylogenetic hypotheses of termites in this, the oldest DNA yet characterized.
Each year, 5% of all coronary artery bypass operations are repeat procedures, and 15%-30% of coronary artery vein grafts occlude within the first eighteen months postoperatively. To evaluate the macroscopic and histologic effects of G-lasing on vein grafts and their patency, femoral veins were used to bypass bilaterally induced stenoses of femoral arteries in 10 dogs. The left vein grafts were G-lased with a 1.5 mm, hot-tipped argon laser at 5 watts for ninety seconds, while the right grafts were used as the controls. Acutely, each vein graft demonstrated no evidence of charring or perforation. The percentage of endothelium present in the G-lased vein grafts was consistently less than 5%, whereas the control vein grafts had an average of 70%. After ten weeks, the animals were sacrificed, and the vein grafts were evaluated for histologic changes and patency. There were no significant microscopic differences between the G-lased and control vein grafts. A statistically significant difference in graft patency was not achieved between G-Lased and control vein grafts at 10 weeks, but only a small number of grafts were studied. Further studies will be needed to evaluate the effects of G-lasing on the long-term patency of vein grafts.
Seventy-five patients more than fifty years of age were admitted for treatment of burns from January 1, 1986, to December 31, 1987, to two community-hospital-based burn units. Patients were managed by a team of burn surgeons at each unit and early excision and grafting was used whenever possible in deep partial-thickness and full-thickness burns. The extent of burn was charted weekly during hospitalization and rate of wound healing was calculated using linear regression analysis. The mean total percent burn was 26.2 per cent (range, 4-85%). The overall mortality rate was 40 per cent. Mortality rate increased sharply by decade from 17.4 per cent for those aged 50-59 years to 100 per cent for the five patients age 90 and more. Excision and grafting were performed in 40 patients; 35 patients were not operated upon. Although hospitalization was somewhat longer in patients treated surgically, survival was better. Excision and grafting should be used when needed to achieve rapid wound closure in patients more than fifty years of age.
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Pancreatic ectasia (PE) is a common incidental finding in people dying from uremia. It has been described as dilatation of acini, inspissation of secretions, and proliferation of ductal cells. PE occurred in 17 macaques, 11 of which were known to have been uremic. The lesion was studied by light and electronmicroscopy and histochemistry and by construction of a three-dimensional model of a dilated acinar ductal system from serial semithick Epon sections. Atrophic acinar cells interspersed with clumps of centroacinar cells lined all portions of the system. There was no evidence of ductular proliferation. Fibrillar material was present in the dilated acinar lumens and associated with epithelial cells and leukocytes, but no blockage of the system was demonstrated. The lesion is similar to those induced by a variety of experimental procedures and to the pancreatic lesions of cystic fibrosis.
Phase I studies were conducted in 58 adult cancer patients with Baker's Antifol (BAF), a new active-site directed inhibitor of dihydrofolate reductase. Dose escalation ranged from 10 to 250 mg/m2/day X 5 days and courses of treatment were repeated every 2-3 weeks. Biologic effects were observed mostly at doses greater than 100 mg/m2/day X 5 days. The patients developed myelosuppression during 19% of the trials. Other types of toxicity were dermatitis in 12 to 30% and stomatitis in 7 to 38% of the trials. Toxicity was directly related to the impairment of the patient's liver function. Two partial responses (in a patient with adenocarcinoma of the lung and a patient with transitional cell carcinoma of the bladder) occurred. BAF is an active new chemotherapeutic agent which deserves further clinical trials in patients with various malignancies.
Five cases of painful bone resorption from the distal clavicle following shoulder trauma are reported to demonstrate that the lesion is generally benign. Surgical excision is curative. The multiplicity of circumstances leading to clavicular osteolysis suggest that the balance between bone accretion and resorption is precarious in this region of the skeleton.