Biomedical subjects
Publications and source records attributed to D Long.
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Our study aimed to determine the least number of samples that are required to obtain accurate pharmacokinetic parameters in neonates. Patients treated with either netilmicin or ceftazidime had between five and eight samples drawn for drug concentration measurement after the first or the last dose of the drug. Pharmacokinetic parameters were calculated using all the available points as a reference and then recalculated with 2, 3, or 4 points. Systemic clearance and volume of distribution were significantly different from the reference value when 2 points were used for netilmicin after the first dose and ceftazidime after the last dose. Had parameters obtained from 2 points been used, mean dosage would have been underestimated by 15% for ceftazidime and 11% for netilmicin, and some patients would have received only 65% of the dose calculated from all available points. When 3 points were used, dosage would have been underestimated by a mean of only 1% for ceftazidime and 5% for netilmicin when compared with the dosage estimated from the reference parameters. We conclude that 3 concentration time points may be all that are required for estimation of pharmacokinetic parameters sufficiently accurate for practical purposes in neonates.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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We have studied the effects of supervised caloric restriction and exercise on mononuclear leukocyte lipid composition, membrane fluidity, and insulin receptors in ten nondiabetic obese adults, (175 +/- 9.3% of ideal body weight) and ten normal adult subjects. In a second study, we examined the effects of caloric restriction alone using a very low calorie liquid diet in the treatment of another ten obese adults. In both groups of obese adults, fasting insulin levels were elevated and fell to normal levels following treatment. Insulin binding to monocytes, which was reduced in obese subjects, increased toward normal after short-term treatment; this was due to the restoration of total insulin binding capacity to levels one half of that seen in the normal adult group. Obese subjects undergoing either treatment had elevated membrane cholesterol/phospholipid ratios prior to treatment (0.499 +/- 0.050 and 0.446 +/- 0.011 v 0.400 +/- 0.025 mol/mol in normal adults P less than 0.005 by ANOVA). Prior to treatment, for all subjects there was a significant inverse correlation between insulin tracer binding and membrane cholesterol/phospholipid ratios (r = .484, n = 34, P less than 0.005). This relationship did not change significantly in obese subjects in either treatment group. Cell membrane microviscosity was determined by fluorescence polarization (FP) using DPH (2 X 10(-6) mol/L). Prior to weight loss, obese subjects had significantly higher FP values than controls (0.304 +/- 0.006 and 0.319 v 0.259 +/- 0.009, P less than 0.005, by ANOVA) indicating greater microviscosity.(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence of pneumocephalus and factors contributing to its occurrence were studied retrospectively in 100 consecutive patients who underwent posterior fossa or cervical cord surgery in the sitting, park-bench, and prone positions. Supine skull x-ray films taken immediately postoperatively were used to determine the presence of intracranial air. Surgery in the sitting position uniformly resulted in pneumocephalus (32/32 patients). Pneumocephalus also occurred frequently among patients in the park-bench (29/40) and prone positions (16/28). Intraventricular air occurred more frequently when patients were in the sitting position (25/32) than in the two other surgical positions (3/29 and 4/16, respectively, P less than 0.001). The high incidence of pneumocephalus and of intraventricular air that occurred when patients were in the sitting position is attributed to the large amount of cerebrospinal fluid drained due to gravitational effect. When surgical position is considered one of the contributing factors, only positions significantly affected the frequencies of pneumocephalus and intraventricular air accumulation. None of the 77 patients with pneumocephalus suffered neurologic change related to the presence of intracranial air. We conclude the following: pneumocephalus commonly occurs after posterior fossa or cervical cord surgeries, particularly when the surgery is performed in the sitting position; neurologic change caused by pneumocephalus is a rare complication after posterior fossa craniotomy; when a patient with coexisting hydrocephalus undergoes surgery, if the patient is in the sitting position, there is an increased risk of trapping a large amount of intracranial air.
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In a double-masked, randomized, comparison titration study to determine the effective dose of topically applied levobunolol, three concentrations of levobunolol (0.25%, 0.5%, and 1%) and of timolol (0.125%, 0.25%, and 0.5%) were evaluated in patients with mild open-angle glaucoma or ocular hypertension. Following a washout of ocular hypotensive medication, twice-daily treatment in both eyes was initiated with the lowest of the three doses of either drug. The concentration was increased if intraocular pressure remained uncontrolled. Intraocular pressure was controlled in 63% (15 of 24) of the patients tested with the lowest concentration of levobunolol and 69% (18 of 26) with the lowest concentration of timolol. Overall, 75% (18 of 24) of the patients in the levobunolol group and 73% (19 of 26) of the patients in the timolol group had adequately controlled intraocular pressure. At the lowest concentrations tested, mean decreases from baseline in intraocular pressure ranged from 6 to 8 mm Hg in both treatment groups.
The gene for hereditary retinoblastoma (Rb), an autosomal dominant trait localized to the long arm of chromosome 13, is linked to the locus for the enzyme esterase D (EsD). We analyzed a three-generation family that demonstrates cosegregation of alleles at the EsD locus and the Rb locus. This kindred yields a logarithm of the odds ratio (LOD) score of 2.46 at a recombination fraction (0) of 0.0. When combined with five other recently reported families, the resulting maximum score was 11.08 at 0 = 0.0. This combined LOD score and the lack of demonstrable crossovers in more than 65 individuals indicate that predictions of the Rb gene carrier state based on EsD genotyping are at least 90% accurate.
We previously defined eight groups of monoclonal antibodies which react with distinct epitopes of herpes simplex virus glycoprotein D (gD). One of these, group VII antibody, was shown to react with a type-common continuous epitope within residues 11 to 19 of the mature glycoprotein (residues 36 to 44 of the predicted sequence of gD). In the current investigation, we have localized the sites of binding of two additional antibody groups which recognize continuous epitopes of gD. The use of truncated forms of gD as well as computer predictions of secondary structure and hydrophilicity were instrumental in locating these epitopes and choosing synthetic peptides to mimic their reactivity. Group II antibodies, which are type common, react with an epitope within residues 268 to 287 of the mature glycoprotein (residues 293 to 312 of the predicted sequence). Group V antibodies, which are gD-1 specific, react with an epitope within residues 340 to 356 of the mature protein (residues 365 to 381 of the predicted sequence). Four additional groups of monoclonal antibodies appear to react with discontinuous epitopes of gD-1, since the reactivity of these antibodies was lost when the glycoprotein was denatured by reduction and alkylation. Truncated forms of gD were used to localize these four epitopes to the first 260 amino acids of the mature protein. Competition experiments were used to assess the relative positions of binding of various pairs of monoclonal antibodies. In several cases, when one antibody was bound, there was no interference with the binding of an antibody from another group, indicating that the epitopes were distinct. However, in other cases, there was competition, indicating that these epitopes might share some common amino acids.
Glycoprotein D (gD) of herpes simplex virus (HSV) protects mice from a lethal challenge by either HSV type 1 (HSV-1; oral) or HSV-2 (genital). We evaluated whether synthetic peptides representing residues 1 through 23 of gD (mature protein) can be used as a potential synthetic herpesvirus vaccine. The immunogenicity of the peptides was demonstrated by the biological reactivity of antipeptide sera in immunoprecipitation and neutralization assays. All sera which immunoprecipitated gD had neutralizing against both HSV-1 and HSV-2. The highest titers were found in animals immunized with the longest peptides. The region of residues 1 through 23 was immunogenic regardless of whether the type 1 or type 2 sequence was presented to the animal. Immunization of mice with gD or synthetic peptides conferred solid protection against a footpad challenge with HSV-2. However, the peptides were not as effective as gD in protection against an intraperitoneal challenge. The results suggested that synthetic vaccines based on gD show promise and should be more rigorously tested in a variety of animal models.
Two patients with Addison's disease related to urogenital tuberculosis had enlargement of one or both adrenal glands detected with computed tomographic scanning. Review of reports of adrenal size on computed tomographic examination suggests that adrenal enlargement in the presence of Addison's disease demands further investigation about the cause of the adrenal insufficiency.
Glycoprotein D is a virion envelope component of herpes simplex virus types 1 and 2. Sets of mice were immunized with purified gD-1 or gD-2 and were challenged with a lethal dose of herpes simple virus, either type 1 or type 2. All or virtually all of the immunized mice survived challenge with either agent, whereas challenge of sham-immunized mice was almost always fatal. Serum samples taken before challenge contained gD-specific antibodies which had 50% neutralization titers ranging from 1:16 to 1:512 against homologous and heterologous virus types. We conclude that either gD-1 or gD-2 is a potential candidate for a subunit vaccine against herpetic infections.
An antigenic determinant capable of inducing type-common herpes simplex virus (HSV)-neutralizing antibodies has been located on glycoprotein D (gD) of HSV type 1 (HSV-1). A peptide of 16 amino acids corresponding to residues 8 to 23 of the mature glycoprotein (residues 33 to 48 of the predicted gD-1 sequence) was synthesized. This peptide reacted with an anti-gD monoclonal antibody (group VII) previously shown to neutralize the infectivity of HSV-1 and HSV-2. The peptide was also recognized by polyclonal antibodies prepared against purified gD-1 but was less reactive with anti-gD-2 sera. Sera from animals immunized with the synthetic peptide reacted with native gD and neutralized both HSV-1 and HSV-2.
Glycoprotein D (gD) of herpes simplex virus is a structural component of the virion envelope which stimulates production of high titers of herpes simplex virus type-common neutralizing antibody. We carried out automated N-terminal amino acid sequencing studies on radiolabeled preparations of gD-1 (gD of herpes simplex virus type 1) and gD-2 (gD of herpes simplex virus type 2). Although some differences were noted, particularly in the methionine and alanine profiles for gD-1 and gD-2, the amino acid sequence of a number of the first 30 residues of the amino terminus of gD-1 and gD-2 appears to be quite similar. For both proteins, the first residue is a lysine. When we compared our sequence data for gD-1 with those predicted by nucleic acid sequencing, the two sequences could be aligned (with one exception) starting at residue 26 (lysine) of the predicted sequence. Thus, the first 25 amino acids of the predicted sequence are absent from the polypeptides isolated from infected cells.