The flood, The Hague and the mosquito.
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Biomedical subjects
Publications and source records attributed to E Gill.
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An extended-duration formulation of lambda-cyhalothrin (Demand CS) applied as either an ultra-low volume (ULV) or thermal fog spray from a new handheld sprayer (Terrier) against Aedes aegypti was evaluated in Honduras. Spray applications were made at the front door for 1 min or to each room for 15 sec, both for the ULV and thermal fog applications to houses in separate blocks for each treatment. The efficacy and duration of effectiveness of the spray was determined from sentinel caged mosquito mortality and collection of mosquitoes within houses with a backpack power aspirator. Sentinel caged mosquito mortality in both open and sequestered locations was 97-100% for all spray treatments, with control mortality less than 2%. Both ULV applications (front door and each room) provided 4 wk of significant control (P < 0.01) based on adult Ae. aegypti house collections.
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The polyglutamine tract, beginning at codon 75 in the N-terminal modulatory domain of rat glucocorticoid receptor (rGR), was analyzed in 61 inbred strains and 155 wild caught Rattus norvegicus. A discontinuous distribution of repeat lengths was found (7, 17-23 repeats). To investigate the possible significance of this distribution, full-length rGR cDNAs with 7, 18, 20, and 21 CAG repeats were expressed in CV-1 cells, and the resulting GR protein analyzed by Western blots and extensive Scatchard analyses. The quantity and steroid binding capacity of GR, together with the binding affinities for dexamethasone and corticosterone, were found to be indistinguishable for the four repeat alleles. From the sequencing of four inbred strains CAG repeat variants were found to be flanked by silent allelic substitutions at nucleotide positions 198, 531, and 711. The four variable sites extended over 471-519 bp of coding sequence, forming six Grl haplotypes. The results are discussed in the light of genetic studies on the Milan hypertensive and normotensive strains of rat. Codon sequence of rat GR required amendment at the following residues: D98, G226, D260, P600, and F602.
A Plasmodium lactate dehydrogenase dipstick designed to separately detect P. falciparum and P. vivax malaria was evaluated in two Honduran populations where both species are endemic. The dipstick was compared to thick film microscopy; the polymerase chain reaction (PCR) was used to analyze discordant results. The dipstick had a sensitivity of 100% and a specificity of 95% compared with microscopy in the diagnosis of Plasmodium infections in a hospital population; the mean parasite density was approximately 590/mm3. In a field sample of mostly asymptomatic volunteers, the sensitivity of the dipstick for Plasmodium infection varied with parasite density. Additionally, the sensitivity and specificity of the dipstick was similar to thick film microscopy in the diagnosis of vivax malaria compared with the PCR. The dipstick was unable to detect P. vivax in the presence of P. falciparum because of cross-reactivity in the pan-specific band. Accurate species identification in mixed infections remains a problem in malaria diagnosis.
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Cytochrome P450cam catalyzes the 5-exo-hydroxylation of camphor. Camphor analogues were designed to fill an empty region of the substrate binding pocket with the expectation that they would bind more tightly than camphor itself due to increased van der Waals interactions with the protein and the displacement of any solvent occupying this site. A series of compounds (endo-borneol methyl ether, endo-borneol propyl ether, endo-borneol allyl ether and endo-borneol dimethyl allyl ether) were synthesized with substituents at the camphor carbonyl oxygen. The spin conversion and thermodynamic properties of this series of compounds were measured for wild type and Y96F mutant cytochrome P450cam and were interpreted in the context of molecular dynamics simulations of the camphor analogues in the P450 binding site and in solution. Compounds with a 3-carbon chain substituent were predicted to match the size of the unoccupied region most optimally and thus bind best. Consistent with this prediction, the borneol allyl ether binds to cytochrome P450cam with highest affinity with a Kd = 0.6 +/- 0.1 microM (compared to a Kd = 1.7 +/- 0.2 microM for camphor under the same experimental conditions). Binding of the camphor analogues to the Y96F mutant is much enhanced over the binding of camphor, indicating that hydrogen bonding plays a less important role in binding of these analogues. Binding enthalpies calculated from the simulations, taking all solvent contributions into account, agree very well with experimental binding enthalpies. Binding affinity is not however correlated with the calculated binding enthalpy because the binding of the substrate analogues is characterized by enthalpy-entropy compensation. The new compounds are useful probes for further studies of the mechanism of cytochrome P450cam due to their high binding affinities and high spin properties.
Heart rate variations during sleep have been documented for infant and adult populations, but not for children and adolescents. To provide normative data for the preadolescent age group, this investigation used a combination of time-domain measures and nonlinear procedures (Poincare plots) to describe heart rate variations during two consecutive nights of undisturbed baseline sleep in 14 normal 8- to 10-year-old males. Heart rate variables, based on all-night analyses of computer-determined beat-to-beat (RR) intervals, were related to sleep stage and sleep cycle measures within and across nights. Time-domain summary statistics revealed a tendency for higher mean heart rates in rapid eye movement (REM) compared to slow-wave (SW) and stage 2 sleep, but the differences were not significant. Heart rate variability, as measured by average RR interval standard deviation, was greatest in stage 2 and least in SW sleep, but it did not vary significantly across sleep stages. Analyses of heart rate variables across the initial four sleep cycles showed a significant heart rate decrease (quadratic trend) and a significant increase (linear trend) for heart rate variability. All effects replicated across nights. Poincare plots revealed wide-ranging individual differences, generally characterized by greater dispersion at longer RR intervals and a remarkable night-to-night consistency in whole-night as well as stage-specific patterns. The sleep-stage plots uniformly indicated reduced overall range and variability in SW relative to REM and stage 2 and a general equivalence of stage 2 and REM patterns. The results indicate several features of sleep-related heart rate variations in preadolescents that differ from those in adults. The differences can be attributed to developmental variations in autonomic cardiac control and are consistent with increased parasympathetic influences reported to occur at this time.
The effect of hydrostatic pressure on the electronic absorption spectrum of the carbon monoxide complex of cytochrome P-450cam (CYP101) in the presence of various substrates was studied. With increasing pressure the wavenumber of the Soret band in the cytochrome P-450-CO complex shifts linearily to lower values (red-shift) and the half-width increases (broadening). The microscopic theory of solvent-solute interaction discussed by Laird and Skinner is used to explain the observed pressure effects. According to this theory, the slope of the red-shift of the Soret band is related to the compressibility of the chromophore environment, that is the heme moiety of the hemoproteins. It was found that the slope of the red-shift and the slope of the broadening of the Soret band for the CO complex in the presence of various substrate analogues increase with the decrease of the initial high-spin content at 0.1 MPa in the oxidized state. Variation of the high-spin content reflects the changes in the number of water molecules and/or changes in the polarity of the heme environment. The higher compressibility of the cytochrome P-450 complexes with the substrate analogues, which induce a lower degree of the high-spin content in the oxidized protein, is explained by the ability of the water molecules in the heme moiety to transmit the pressure effect on the protein structure to the heme chromophore. Therefore, a larger pressure-induced red-shift of the Soret band in the CO complex of cytochrome P-450cam might indicate a higher water content in the heme environment.
13CO NMR chemical shifts and 12CO infrared stretching frequencies have been measured for cytochrome P-450cam-CO in the presence of D-camphor and of various camphor analogues. A linear correlation between both parameters delta (13C) and v(CO) was found indicating that the steric and electrostatic interactions acting on the CO ligand are influenced by the substrate. It has been proved that P-450 complexes are on another line in this correlation than hemoglobins which is explained by the different proximal ligand.
The pharmacokinetics of IV and oral cephradine in healthy young male and female volunteers (ages 19 to 25, n = 10) were compared to those of older individuals (ages 65 to 81, n = 9). Subjects received 1 gram of cephradine by a 5-minute intravenous (IV) infusion followed the next day by a 1-gram oral dose. Serial serum and urine samples collected over a period of 12 hours after the dose were analyzed for cephradine concentration by a microbiologic assay. After IV administration, mean serum cephradine concentrations in the elderly group were significantly higher at both 6 hours (1.52 +/- 0.41 mcg/mL) and 8 hours (0.73 +/- 0.22 mcg/mL) than in the young group at 6 hours (0.43 +/- 0.11 mcg/mL). Total systemic clearance was significantly lower (2.64 +/- 0.34 vs. 4.81 +/- 0.59 ml/min/kg) and the elimination half-life was significantly longer (1.71 +/- 0.20 vs 1.12 +/- 0.13 hours) in the elderly group (P = .0001). Systemic cephradine clearance correlated positively with creatinine clearance (r2 = 0.34, P = .0110) and negatively with age (r2 = 0.79, P = .0052). The mean volume of distribution was not significantly different between the two groups. Mean renal clearance was significantly lower in the elderly group (P = .0001), but more than 80% of the dose was excreted in the urine within 6 hours in both groups. After oral administration, the mean peak concentration and time to peak concentration did not differ between groups. The relative oral bioavailability was approximately 94% in both groups. The mean serum concentrations in the elderly were higher at both 6 and 8 hours than in the young group at 6 hours. There were no differences in pharmacokinetic parameters between male and female subjects. Because of reduced cephradine clearance secondary to an age-related decline in renal function, administration of cephradine every 8 hours, rather than every 6 hours, may be sufficient in elderly patients.
In 7 patients with therapy-resistant pneumothorax and a contraindication of surgery in obstructive large-bullae pulmonary emphysema, pulmonary fibrosis in the terminal stage (in one case bilateral), extensive pulmonary cysts, cystic pulmonary fibrosis, and large-cavernous pulmonary tuberculosis, an acrylate tissue adhesive was applied on 8 occasions through a pleural catheter. Following the rapid withdrawal of the catheter, the lungs remained fully expanded in five cases. In two cases, the tissue adhesive had to be applied interpleurally a second time, and in one case on three occasions at one-day intervals. In none of these cases did any major complications occur.
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Determination of clinically significant temporal changes in P100 latency requires knowledge of the degree of normal intraindividual variability. Checkerboard visual evoked potentials using 3 check sizes (17', 35' and 70') were performed serially on 20 healthy volunteers. Each subject was tested at least twice an average of 6 months apart. The P100 latency was measured at Oz with a forehead reference (Pz, O1 and O2 channels were also recorded). The overall average P100 latency change between studies for all check sizes and both eyes was 2.9 msec. However, the maximum absolute latency change was 11 msec. There was no significant difference between the average latency change for the 3 check sizes. The P100 interocular difference changed a mean of 2.5 msec (maximum 9 msec). Amplitude was more variable, with a mean change of about 1.5 microV or 25% (maximum was a 60% decrease in amplitude). A P100 latency change of up to at least 11 msec needs to be acknowledged as normal when assessing the clinical significance of changes in P100 latencies in patients. Also, P100 latency changes greater than 11 or 12 msec are very suggestive of an abnormality in the visual pathway.
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We used electronic fluorography to perform hysterosalpingography in 25 women with infertility or abnormal bleeding. In contrast to the conventional modality of fluoroscopy with intermittent permanent imaging, an image intensifier was used to periodically record dye injection on a moving tape (cine hysterosalpingography). The mean number of electronic fluorographs taken per patient was 10.8 +/- 3.12 (mean +/- SD). The mean radiation exposure per patient for electronic fluorography was 113.4 +/- 52 versus 112 +/- 52.4 mR when a single conventional radiographic image was taken. We conclude that electronic fluorography is a simple yet accurate radiographic method that delivers to the gonads approximately one-eleventh the dose of ionizing radiation that current standard techniques do, and should be accepted as an alternative diagnostic modality.
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