Debate on cot death. In 1994, 29% of suspicious deaths were officially recorded as due to sudden infant death syndrome.
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Diagnostic Errors↗
Biomedical subjects
S Duncan
Publications and source records attributed to S Duncan.
A required mind-set for child protection practice: comments on Munro (1999)
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Child↗
Antiepileptic drug therapy and sexual function in men with epilepsy.
PURPOSE: To study the effects of antiepileptic drugs (AEDs) on sex hormone levels and sexual activity in a group of men attending a hospital-based epilepsy clinic. METHODS: One hundred eighteen men being treated with AED therapy, 32 with epilepsy but not receiving AEDs, and 34 controls were recruited. All subjects were aged 18-65 years. Blood (20 ml) was removed for hormone assays, after which each subject completed a validated questionnaire [Sexuality Experience Scores (Frenken and Vennix, 1981)] aimed at exploring the individuals' sexual activity and attitudes to sexual morality. RESULTS: Men taking carbamazepine (CBZ) only had significantly higher mean sex hormone-binding globulin (SHBG) levels than the control group. The CBZ group also had a significantly lower mean DHEAS concentration than the control, untreated, and sodium valproate (VPA) monotherapy groups. The phenytoin monotherapy group (PHT) had a significantly higher mean SHBG than both the control and untreated groups, and had a significantly higher mean total testosterone (TT) value than the control untreated, CBZ, and VPA groups, and a significantly lower mean DHEAS than the controls, untreated, and VPA groups. Men receiving more than one AED had significantly higher mean SHBG concentrations compared with control, untreated, and VPA groups. In addition, the polytherapy group's mean TT was significantly higher than the control and VPA groups, although its mean DHEAS concentration was lower than the control, untreated, and VPA groups. There were no significant differences between the study groups in mean FT, Budrostenedione (AND), or estradiol levels. But the CBZ, PHT, and polytherapy groups had significantly lower mean free and rogen index (FAI) than the controls. The CBZ group had a lower mean FAI than the VPA group. The polytherapy group had a lower FAI than the untreated group. Sexuality Experience Scores (SES) showed that those men receiving AEDs embraced a stricter sexual morality than the controls and untreated, and expressed greater satisfaction with their marriages than the control and untreated groups. CONCLUSIONS: Seizure type did not affect SES scores. Multiple regression showed men who had received further education were less accepting of strict sexual morality.
Adolescent↗
Intrapulmonary concentrations of pyrazinamide.
The objective of this study was to compare the steady-state plasma and intrapulmonary concentrations of orally administered pyrazinamide in normal volunteers and subjects with AIDS. Pyrazinamide was administered at 1 g once daily for 5 days to 40 adult volunteers (10 men with AIDS, 10 normal men, 10 women with AIDS, and 10 normal women). Subjects with AIDS and with more than four stools per day were excluded. Blood was obtained prior to administration of the first dose, 2 h after the last dose, and at the completion of bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method. The total number of alveolar cells (AC) was counted in a hemocytometer, and differential cell counting was performed after cytocentrifugation. Pyrazinamide was measured by high-performance liquid chromatography. The presence of AIDS or gender had no significant effect on the concentrations of pyrazinamide in plasma. The concentrations of pyrazinamide in ELF and AC were lower in the subjects with AIDS than in the subjects without AIDS, but the difference was not significant. The concentrations in plasma (mean +/- standard deviation) were 25.1 +/- 7.6 and 21.1 +/- 6.8 microg/ml at 2 and 4 h after the last dose, respectively, and were not significantly different from the concentration (17.4 +/- 16.9 microg/ml) in AC. The concentration of pyrazinamide in ELF was high (431 +/- 220 microg/ml) and was approximately 4 to 40 times the reported MIC for pyrazinamide-susceptible strains of Mycobacterium tuberculosis. The high concentration of pyrazinamide in ELF may contribute in part to the effectiveness of the drug in treating pulmonary tuberculosis.
Acquired Immunodeficiency Syndrome↗
Sexual function in women with epilepsy.
PURPOSE: To examine certain aspects of sexual behaviour and attitudes in a group of women with epilepsy using a validated questionnaire (Sexuality Experience Scales), and effects of antiepileptic drugs (AEDs) on sex hormone binding globulin (SHBG), total testosterone (TT), and free testosterone (FT). METHODS: One hundred ninety-five women all attending a hospital-based epilepsy clinic were recruited. One hundred fifty-nine received AED therapy and 36 women did not. A control group of 48 women was also recruited. All women completed the first two Sexuality Experience Scales (SES 1 and SES 2), and those women in stable heterosexual relationships completed SES 3 and SES 4. At the same time blood was taken for TT and SHBG levels. FT was calculated using the method of Nanjee and Wheeler (22). RESULTS: Women receiving AED therapy achieved significantly higher SES 1 and SES 2 scores than the rest of the women, suggesting that they adhered to a stricter sexual morality and were less open to psychosexual stimulation than the rest of the women treated. Women in the treated group were less likely to have received further education than the controls, a factor that influences SES 1 and SES 2 scores. There were no significant differences between the three groups on SES 3 or SES 4, with the exception of the orgasmic adequacy (OE) scale of SES 3 where those women in the treated group attained a higher mean score than the controls, suggesting that they found orgasm less satisfying. Women receiving AEDs had significantly higher SHBG and TT than controls and untreated patients. There were no differences in FT between the groups. Those women receiving AEDs also exhibited the expected midcycle rise in FT. There was no significant correlation between FT and the desired frequency of intercourse or enjoyment of it for the three groups. CONCLUSIONS: Women in the treated group appeared to be more "moral" and less open to sexual approach, but those who had regular partners appeared to desire and enjoy intercourse as much as the control and untreated groups. This could be explained by differences in demographic characteristics of the study groups or be indicative of a bimodal distribution of sexual interest in these women. As FT was within physiological norms for each study group this cannot be cited as a cause for hyposexuality.
Anticonvulsants↗
Need probability affects retention: a direct demonstration.
Recent memory theory has emphasized the concept of need probability--that is, the probability that a given piece of learned information will be tested at some point in the future. It has been proposed that, in real-world situations, need probability declines over time and that the memory-loss rate is calibrated to match the progressive reduction in need probability (J.R. Anderson & Schooler, 1991). The present experiments were designed to examine the influence of the slope of the need-probability curve on the slope of the retention curve. On each of several trials, subjects memorized a list of digits, then retained the digits in memory for 1, 2, 4, 8, or 16 sec. Some trials ended with a recall test; other trials ended with the message, "no test." In Experiment 1, the likelihood of encountering a memory test (i.e., the need probability) was made to either increase or decrease as the retention interval increased; in Experiment 2, need probability either was flat (invariant across retention intervals) or decreased as the retention interval increased. The results indicated that the shape of the need-probability curve influenced the slope of the retention curve (Experiment 1) and that the effect became larger as the experimental session progressed (Experiment 2). The findings support the notion that memory adapts to need probabilities and that the rate of forgetting is influenced by the slope of the need-probability curve. In addition, all of the forgetting curves approximated a power function, suggesting that need probability influences the slope but not the form of forgetting.
Educational Measurement↗
Extended lung preservation with platelet-activating factor-antagonist TCV-309 in combination with prostaglandin E1.
BACKGROUND: Ischemia-reperfusion injury is one of the major problems in organ transplantation. The role of platelet-activating factor (PAF) in the pathophysiology of ischemia-reperfusion injury and the protective effect of a novel phospholipid PAF analog (TCV-309) alone and combined with prostaglandin E1 (PGE1) is investigated in an extended (20 hours) ex vivo lung preservation. METHODS: Forty-two swine were divided into three groups. Group A was the control. In groups B and C, the effect of PAF was blocked with TCV-309 administered 1 hour before cross-clamping for donor and recipient. Group C received PGE1 50 micrograms bolus in the donor pulmonary plegia, and the recipients received a 50 micrograms bolus plus 0.003 microgram/kg/min infusion at the time of implantation. Donor lungs were perfused with cold modified Collins solution and maintained in hypothermic storage (4 degrees C) for 20 hours. Hemodynamics, lung mechanics, gas exchange, and biochemistry were assessed before transplantation (donor) and at 30 minutes and 24 hours after reperfusion (recipient). At 24 hours after reperfusion, the histopathologic condition of transplanted lungs was evaluated. RESULTS: Radioimmunoassay demonstrated a significant (p < 0.001) increase in the production of PAF and TXB2 in transplanted lungs at 24 hours after transplantation for group A only. Hemodynamics, gas-exchange parameters, and lung compliance were significantly (p < 0.05) better after transplantation for groups B and C. Wet lung weight was significantly less (p < 0.05) for group C. Semiquantitative morphometric analysis demonstrated the highest degree of damage for group A compared with groups B and C. A strong correlation (r2 = 70) between lung weight and histologic injury scores was observed among groups. CONCLUSIONS: This study suggests that PAF is responsible in part for the deleterious effects of ischemia and reperfusion, that PAF-antagonist TCV-309 protects lungs from extended (20 hours) ischemic injury, and that PGE1 seems to have an additional beneficial effect.
Alprostadil↗
Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects.
The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithormycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four subjects each, the subjects underwent bronchoscopy and bronchoalveolar lavage at timed intervals following drug administration. Drug concentrations, including those of 14-hydroxyclarithromycin (14H), were determined in serum, bronchoalveolar lavage fluid, and alveolar cells (ACs) by high-pressure liquid chromatography. Concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. The maximum observed concentrations (mean +/- standard deviation) of azithromycin, clarithromycin, 14H, ciprofloxacin, and cefuroxime in serum were 0.13 +/- 0.07, 1.0 +/- 0.6, 0.60 +/- 0.41, 0.95 +/- 0.32, and 1.1 +/- 0.3 microgram/ml, respectively (all at 6 h). None of the antibiotics except clarithromycin (39.6 +/- 41.1 micrograms/ml) was detectable in ELF at the 6-h bronchoscopy. The movement into and persistence in cells was different for azithromycin and clarithromycin. In ACs azithromycin was not detectable at 6 h, reached its highest concentration at 120 h, and exhibited the greatest area under the curve (7,403 micrograms.hr ml-1). The peak concentration of clarithromycin (181 +/- 94.1 micrograms/ml) was greater and occurred earlier (6 h), but the area under the curve (2,006 micrograms.hr ml-1) was less than that observed for azithromycin. 14H was detectable in ACs at 6 h (40.3 +/- 5.2 micrograms/ml) and 12 h (32.8 +/- 57.2 micrograms/ml). The peak concentration of ciprofloxacin occurred at 6 h (4.3 +/- 5.2 micrograms/ml), and the area under the curve was 35.0 micrograms.hr ml-1. The data indicate that after the administration of a single dose, azithromycin, clarithromycin, and ciprofloxacin penetrated into ACs in therapeutic concentrations and that only clarithromycin was present in ELF. The correlation of these kinetic observations with clinical efficacy or toxicity was not investigated and is unclear, but the data provide a basis for further kinetic and clinical studies.
Administration, Oral↗
Closure, covert warnings, and escalating child abuse.
Research into prevention of child abuse deaths is notoriously difficult, both clinically and methodologically. Korbin (1989) supports the conclusions of Fontana and Alfaro (1987) that it may not be possible to predict which child maltreatment case might result in a fatality. Our study was retrospective, concerned a selected group of cases and was unable to compare cases in which closure or approaches to professionals did not culminate in a child's death. Nonetheless, it points to particular patterns that occur which may help alert practitioners in the field. It is our hope that clinical research based on these observations will enhance the practice of child protection in the future.
Child Abuse↗
Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin.
The intrapulmonary pharmacokinetics of orally administered clarithromycin (500 mg every 12 h for five doses) or erythromycin (250 mg every 6 h for nine doses) were studied in 32 healthy adult volunteers. Four of the subjects, two in the clarithromycin group and two in the erythromycin group, were smokers. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed at 4, 8, 12, 24, and 48 h after administration of the last dose of clarithromycin and at 4, 8, and 12 h after administration of the last dose of erythromycin. Clarithromycin was measured by high-performance liquid chromatography, and erythromycin was measured by a microbiological assay. No systemic sedation was used. There were no major adverse events. The concentrations of antibiotics in epithelial lining fluid (ELF) were calculated by the urea dilution method. The volumes (mean +/- standard deviation) of ELF were 1.9 +/- 2.0 ml and 1.5 +/- 0.7 ml in the clarithromycin and erythromycin groups, respectively (P > 0.05). There was no effect of smoking on the amount of bronchoalveolar lavage fluid recovered, the volume of ELF, or the number of erythrocytes present in the lavage fluid (P > 0.05 for all comparisons). The total number of alveolar cells, however, was almost threefold greater in the smokers versus that in the nonsmokers (P < 0.05). Clarithromycin was concentrated in ELF (range, 72.1 +/- 73.0 micrograms/ml at 8 h to 11.9 +/- 3.6 micrograms/ml at 24 h) and alveolar cells (range, 505.8 +/- 293.1 micrograms/ml at 4 h to 17.0 +/- 34.0 micrograms/ml at 48 h). 14-(R)-Hydroxyclarithromycin was also present in these compartments, but at lower concentrations than the parent compound. The concentrations of erythromycin in ELF and alveolar cells were low at 4, 8, and 12 h following the last dose of drug (range, 0 to 0.8 +/- microgram/ml in ELF and 0 to 0.8 +/- 1.3 microgram/ml in alveolar cells). The clinical significance of any antibiotic concentrations in these compartments in unclear. The data suggest, and we conclude, that clarithromycin may be a useful drug in the treatment of pulmonary infections, particularly those caused by intracellular organisms.
Adult↗
Interactions of intestinal mediators in the mode of action of cholera toxin.
Cholera toxin (CT) and prostaglandin E2 (PGE2) increased the synthesis of 3',5'-cyclic adenosine monophosphate (cAMP) in rabbit intestinal mucosa, which appeared to be responsible for inducing the release of 5-hydroxytryptamine (5-HT) from enterochromaffin cells into the intestinal lumen. With isolated intestinal cells, CT induced the synthesis of PGE2 more efficiently from epithelial cells than from lamina propria cells; however, the basal amount of this eicosanoid produced by lamina propria cells was approximately six-fold more than that formed by the epithelial cells. The CT-induced stimulation of arachidonate metabolism appeared to be generalised in nature, as PGF2 alpha and leukotrienes were synthesised in addition to PGE2. Injection of dibutyryl cAMP into the intestinal lumen in vivo markedly reduced both basal levels of PGE2, as well as CT-induced levels of PGE2, released into the luminal fluid. Similarly, when biopsy samples of tissue from rabbit intestinal loops, challenged in vivo with dibutyryl cAMP, were washed and incubated in vitro, the amount of PGE2 synthesis remained below basal levels. In contrast, when biopsy samples of normal small intestinal tissue were exposed in vitro to dibutyryl cAMP, PGE2 synthesis increased. Thus, cAMP appeared to down-regulate the levels of intestinal eicosanoids in vivo, despite its innate capacity to evoke PGE2 synthesis from mucosal tissue in vitro. Thus, the data indicate that CT-induced mediators exhibit interactive effects that alter their cellular concentrations, that in turn could affect the biological responses.
Animals↗
Luminescence-based detection of activity of starved and viable but nonculturable bacteria.
A naturally luminescent bacterium, Vibrio harveyi, and two bacteria, Escherichia coli and Pseudomonas fluorescens, which had been genetically marked with luminescence were starved in liquid medium at 4 and 30 degrees C for 54 days. Total cell concentrations and concentrations of culturable and viable cells were determined by acridine orange staining, dilution plate counting, and direct viable counting, respectively, and population activity was measured by luminometry. V. harveyi became nonculturable but maintained viability during starvation at 4 degrees C and maintained both culturability and viability at 30 degrees C. In contrast, E. coli became viable but nonculturable during starvation at 30 degrees C but not at 4 degrees C. Luminescence of nonculturable cells of both strains, and culturable cells of V. harveyi, decreased to background levels during starvation. Luminescence of starved culturable cells of E. coli also fell below background levels but occasionally increased to detectable values. Viable, nonculturable forms of P. fluorescens were not detected at either temperature, and cells starved at 4 degrees C showed no decrease in luminescence measured during incubation of samples at 25 degrees C. Following incubation of late-log-phase cells with yeast extract and nalidixic acid, changes in light output directly paralleled changes in cell length, as observed during direct viable counting. Quantification of changes in luminescence following incubation of starved cells with yeast extract enabled measurement of the activity of both culturable and viable but nonculturable cells. Measurement of luminescence was significantly more sensitive, rapid, and convenient in quantifying activity following nutrient amendment than measurement of changes in cell length.(ABSTRACT TRUNCATED AT 250 WORDS)
Bacteria↗
Kindergarten predictors of first-grade reading achievement: a regular classroom sample.
Routinely collected measures for 38 children in the kindergarten program in a middle-class school in a small midwestern city were analyzed as predictors of first-grade reading achievement on the Iowa Tests of Basic Skills and of first-grade performance on the Cognitive Abilities Test. Correlations among all variables are given. Stepwise multiple regression analyses predicting the first-grade variables showed that consonant-sound-identification was the best predictor of first-grade reading achievement and that the Peabody Picture Vocabulary Test--Revised was the best predictor of cognitive ability. A second multiple regression analysis examined the contribution of each kindergarten variable to first-grade reading and cognitive scores. Analysis indicated that these children entered kindergarten with highly developed early reading skills which facilitated success with systematic reading instruction.
Achievement↗
Isolation and identification of two cyclosporine aldehydic metabolites from the bile of a liver transplant recipient during an acute nephrotoxic episode.
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Animals↗
Lack of effect of concomitant clobazam on interictal 123I-iomazenil SPECT.
Single photon emission computed tomography (SPECT) is being increasingly used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. Fourteen patients (five male, nine female; mean age 31 years) with refractory complex partial seizures, all of whom had abnormal 99Tc HM-PAO SPECT scans, were imaged again using the benzodiazepine receptor ligand 123I-iomazenil. Eleven of these patients displayed the same abnormality on both scans. The magnitude of the deficit, however, was slightly greater (P < 0.05) on the iomazenil scan compared with the HM-PAO study. These 11 patients were then randomised into two groups. Group 1 (n = 7) received clobazam 20 mg/day for a minimum of 7 days before a second iomazenil study was performed. Patients in group 2 (n = 4) underwent a second iomazenil scan at the same time interval as those in group 1, but without the additional clobazam. The resultant scans were reported blind to treatment. There were no qualitative or quantitative differences between the first and second iomazenil studies in either group. Patients can be imaged using 123I-iomazenil without withdrawing clobazam therapy. From this preliminary study, there seems little advantage in using iomazenil in place of HM-PAO to delineate the extent of the zone of epileptogenesis. Whether iomazenil SPECT will prove to be more sensitive in identifying the site of the epileptic focus remains to be determined.
Adult↗
Molecular mediators formed in the small intestine in response to cholera toxin.
The molecular mechanism of experimental cholera, leading to increased water and electrolyte secretion, was evaluated with the rabbit intestinal loop model. The levels of cyclic adenosine monophosphate (cAMP), prostaglandin E2 (PGE2), and 5-hydroxytryptamine (5-HT) were measured in mucosal tissue or luminal fluids from intestinal segments exposed to cholera toxin (CT). Each mediator increased in a dose-dependent manner coinciding with the amount of fluid accumulating in the CT-treated loops within the 16 h observation period. Interestingly, a substantial amount of the cAMP in the CT loops was released into the intestinal lumen, along with the fluid. Fluid accumulation was evoked by instillation of PGE2 and CT into the intestinal segments, but not by 5-HT. Large doses of dibutyryl cAMP at 50 mg/ml, but not at 25 mg/ml, also evoked fluid accumulation when injected into the intestine. Further, CT evoked the release of 5-HT from the mucosa, although the high doses of cAMP caused a massive release of 5-HT. PGE2 injection was without effect on 5-HT release. Although CT increased the amount of PGE2 into the luminal fluid, no effect on PGE2 levels was observed by injecting any dose of dibutyryl cAMP or 5-HT into the intestinal lumen. Our interpretation of these data is that CT stimulates the independent synthesis and release of both cAMP and PGE2. The cAMP appears to cause the release of 5-HT from the enterochromaffin cells. Since dibutyryl cAMP did not evoke a PGE2 response, it was concluded that cAMP could elicit secretion of fluid without the participation of PGE2; however, the cAMP doses were not physiological.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗