Managed care: the principles approach.
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Beneficence↗
Biomedical subjects
A Thomas
Publications and source records attributed to A Thomas.
Lung diffusion capacity, oxygen uptake, cardiac output and oxygen transport during exercise before and after an himalayan expedition.
Studies were made of pulmonary diffusion capacity and oxygen transport before and after an expedition to altitudes at and above 4900 m. Maximum power (Pmax) and maximal oxygen uptake (VO2max) were measured in 11 mountaineers in an incremental cycle ergometer test (25W.min-1) before and after return from basecamp (30 days at 4900 m or higher). In a second test, cardiac output (Qc) and lung diffusion capacity of carbon monoxide (DL,cg) were measured by acetylene and CO rebreathing at rest and during exercise at low, medium and submaximal intensities. After acclimatization, VO2max and Pmax decreased by 5.1% [from 61.0 (SD 6.2) to 57.9 (SD 10.2) ml.kg-1, n.s.] and 9.9% [from 5.13 (SD 0.66) to 4.62 (SD 0.42) W.kg-1, n.s.], respectively. The maximal cardiac index and DL,cg decreased significantly by 15.6% [14.1 (SD 1.41) 1.min-1.m-2 to 11.9 (SD 1.44)1.min-1.m-2, P < 0.05] and 14.3% [85.9 (SD 4.36) ml.mmHg-1. min-1 to 73.6 (SD 15.2) ml.mmHg-1.min-1, P < 0.05], respectively. The expedition to high altitude led to a decrease in maximal Qc, oxygen uptake and DL,cg. A decrease in muscle mass and capillarity may have been responsible for the decrease in maximal Qc which may have resulted in a decrease of DL,cg and an increase in alveolar-arterial oxygen difference. The decrease in DL,cg especially at lower exercise intensities after the expedition may have been due to a ventilation-perfusion mismatch and changes in blood capacitance. At higher exercise intensities diffusion limitation due to reduced pulmonary capillary contact time may also have occurred.
Acclimatization↗
Long echo time STIR sequence MRI of optic nerves in optic neuritis.
MRI of the optic nerves was obtained in 13 patients with acute optic neuritis and 13 with a previous optic neuritis (ON), assessed by clinical features, visual fields and visual evoked potentials. Results of the conventional short tau inversion recovery (STIR) sequence obtained with a short echo time (STE-STIR; 22 ms) were compared with those of a long echo time (LTE-STIR: 80 ms) sequence. The conventional STE-STIR sequence revealed lesions in the optic nerves in 78.5% of acute and 58.8% of previous ON. The LTE-STIR sequence showed abnormalities in 92.8% of acutely symptomatic nerves and 94.1% of nerves with previous ON. The optic nerve lesions appeared significantly longer with the LTE-STIR sequence than with the conventional STE-STIR sequences, in both acute and previous ON.
Adult↗
Long time echo STIR sequence magnetic resonance imaging of optic nerves in optic neuritis.
Magnetic resonance images of optic nerves were obtained in 20 patients with acute optic neuritis (ON), and assessed by means of clinical, visual field and visual evoked potential evaluations; the imaging was repeated 1 year later. The results of the conventional Short Tau Inversion Recovery (STIR) sequence obtained using short time echo (STE-STIR: 22 msec) were compared with those of the long time echo sequence (LTE-STIR: 80 msec). The conventional STE-STIR sequence revealed lesions in 57.2% cases of acute ON and in 42.9% of the optic nerves affected by previous ON; the LTE-STIR sequence was diagnostic in 95.2% of acute ON cases and in 85% of patients with previous ON. The calculated length of the optic nerve lesions was significantly longer in the images obtained using the LTE-STIR sequence than in those obtained using conventional STE-STIR sequences.
Adult↗
Are VEP abnormalities in optic neuritis (ON) dependent on plaque size? A reappraisal of the physiopathology of ON based on improved MRI and multiple-lead recordings.
Twenty patients with optic neuritis (ON) described in the previous study [23] underwent serial VEP recordings (using multiple electrode arrays) for two years. The VEPs could be correlated with the lesions revealed by MRI, Visual Field tests and other clinical findings. On the basis of their scalp distribution, they were classified as "really delayed" VEPs and "pseudo-delayed" VEPs. Real delays could be recorded at the onset of ON or shortly afterwards, and their appearance indicated the recovery of visual function and a good prognosis. Pseudo-delays indicated an alteration in the visual field and, unless a breakthrough of normal or delayed components appeared in the first three months, following acute ON, indicate a poor prognosis for the recovery of visual function. The pseudo-delayed VEPs were mainly observed in patients with longer lesions revealed by means of LTE-STIR MRI [23]; there was no correlation between VEP latency and the length of plaques. Our findings contradict previous theories on the timing of conduction alterations in ON and multiple sclerosis.
Adult↗
Hypoxic ventilatory response during rest and exercise after a Himalayan expedition.
Hypoxic ventilatory response (HVR) was examined before and after acclimatization to high altitude. Transient hyperoxic switches according to Dejours's technique were used to examine the contribution of HVR to the hyperpnoea of increasing exercise intensities. Ten mountaineers were exposed to hypoxia (oxygen fraction in inspired gas. F1O2 = 0.11, 79 mmHg) before the expedition and after return from altitude (56 days, 30 days at 4900 m or higher). After 25-min breathing hypoxic gas, the subjects performed a maximal cycle ergometer test (increments 50 W per 5 min). Respired gases and ventilation (VE) were analysed breath-by-breath, partial pressure of oxygen (PO2) and oxygen saturation (SO2) were measured in capillary blood. The HVR was tested by switching two breaths to an F1O2 of 1.0. The nadir of VE after the switch was measured (decrease in ventilation, DVE). The HVR was expressed as the DVE at a PO2 of 40 mmHg (DVE40) and the DVE versus decrease of SO2 (DVE/[100-SO2]). The HVR estimated by DVE40 increased from 19.9 to 28.0 l.min-1 (median, P = 0.013). The HVR expressed as DVE (100-SO2) at rest was no different before and after acclimatization (0.89 and 0.86 l.min-1.%-1 respectively) and during exercise it did not change before the expedition (0.83 l.min-1. %-1). However, DVE/(100-SO2) increased significantly with exercise intensity after the expedition (1.61 l.min-1.% at 200 W). The changes of DVE versus SO2 as well as of DVE versus VE were steeper after the expedition than before. In summary, after return from 30 day at high altitude, an increased HVR was observed. The augmentation of HVR was evident at higher exercise intensities and we suggest that this reflects a change in sensitivity of the peripheral chemoreflex loop.
Acclimatization↗
Sequential estrogen and progesterone (P) followed by P withdrawal increases the level of oxytocin messenger ribonucleic acid in the hypothalamic paraventricular nucleus of the male rat.
We previously reported that alterations in gonadal steroid hormones can influence oxytocin (OT) messenger ribonucleic acid (mRNA) expression in the hypothalamic paraventricular nucleus (PVN) of the steroid-treated ovariectomized rat, the pregnant rat, and the lactating rat. Specifically, OT mRNA in the PVN of the female rat was increased by sequential estrogen and progesterone (P) followed by withdrawal of P. In this study we investigated whether this same steroid paradigm increases OT mRNA levels in the castrate rat. Castrate rats were administered either sequential estrogen and P followed by P withdrawal or no steroid treatment prior to sacrifice. PVN OT mRNA was measured by Northern blot hybridization and pituitary OT peptide content by radioimmunoassay (RIA). The steroid-treated rats had increased OT mRNA levels compared to the sham treated rats (p < 0.04), but pituitary OT peptide content was not significantly altered. We conclude that sequential estrogen and P followed by P withdrawal increases PVN OT mRNA in the castrate, as well as the ovariectomized, rat.
Animals↗
Lateralization of memory for music: evidence from the intracarotid sodium amobarbital procedure.
The present study was conducted to determine whether material-specific memory for unfamiliar tonal patterns could be demonstrated for the right temporal lobe during the intracarotid sodium amytal procedure (IAP). Thirty-one patients with intractable complex partial seizures associated with either left temporal lobe epilepsy (LTLE) or right temporal lobe epilepsy (RTLE) underwent assessment of memory for tonal patterns during a baseline phase and right and left cerebral hemisphere anaesthesia during the IAP. Patients were presented unfamiliar tonal patterns which were later selected from a set of distracter patterns. Findings indicated that there was no difference between the LTLE and RTLE patients during injection of the right cerebral hemisphere suggesting no specific involvement of left mesial temporal structures. However, a significant effect was noted during left injection with the LTLE group performing significantly better than the RTLE group. This latter finding supports a specific role of right mesial temporal lobe structures in mediating memory for music.
Adult↗
Failure to induce resistance to cytotoxic drugs in normal lymphocytes.
Lymphocytes from patients who had received chemotherapy for lung cancer were examined for evidence of drug resistance using an in vitro assay for sensitivity to the effects of chlorambucil and etoposide. There was no evidence of induced resistance to the effects of chlorambucil or etoposide in the patients' lymphocytes when compared to the sensitivity of the normal control subjects' lymphocytes. In four patients, in whose lymphocytes sensitivity to chlorambucil was measured before and after a course of treatment, there was no significant change in the in vitro drug sensitivity. These findings are in contrast to those made previously using the lymphocytes of patients with chronic lymphocytic leukaemia and indicate that acquired drug resistance is a property of malignant cells and is not inducible in normal lymphocytes.
Antineoplastic Agents↗
Complement activation on human neuroblastoma cell lines in vitro: route of activation and expression of functional complement regulatory proteins.
Two human neuroblastoma cell lines activated the classical pathway of complement in serum. Activation caused the opsonisation of these cells with complement fragments but with moderate cell killing. Neuroblastoma expressed regulators MCP and CD59 but did not express DAF or CR1. Neutralisation of CD59 rendered the cells susceptible to killing. Neuroblastoma also expressed C1-inhibitor, factor H, clusterin and S-protein. Expression of several regulators was enhanced by incubation with cytokines. Complement inhibition using soluble CRI markedly reduced opsonisation and killing of neuroblastoma. Our results suggest that complement might play a role in neuronal loss and that treatment with complement inhibitors might be of therapeutic value.
Antigens, CD↗
Newborns with hyperbilirubinemia: usefulness of brain stem auditory response evaluation.
We describe brain stem auditory evoked potentials (BAEP) obtained in 48 full-term newborns (20 boys, 28 girls) presenting with high serum total bilirubin concentration (from 238 to 442 mM) without Rhesus of group A, B, O factors incompatibility. Recordings were performed on the 3rd day of life and repeated 5-7 days post-appropriate therapy with photostimulation and exchange transfusion (when bilirubin concentration had decreased below 136 mM). Supplementary recordings were performed 3, 6 and 12 weeks later in order to assess test-retest reliability of components. Mean values of BAEP latencies were compared with those obtained in 40 age-matched control subjects using the same recording procedures. At first recording session (on the 3rd day), latencies of waves III and V obtained in hyperbilirubinemic patients were significantly increased as compared with records in control subjects. Recordings performed 5 to 7 days post-therapy and during subsequent recording sessions showed no significant differences between patients and control groups. Serial neuropsychological evaluations obtained over a 3-year follow-up showed no subsequent neurodevelopmental abnormality for all patients. These findings suggest that hyperbilirubinemia can alter central neurotransmission in auditory brain stem pathways, but this modification is only transient.
Case-Control Studies↗
Vero cytotoxin-producing Escherichia coli, particularly serogroup O157, associated with human infections in England and Wales: 1992-4.
Investigations were performed by the Laboratory of Enteric Pathogens on Vero cytotoxin-producing Escherichia coli (VTEC) in England and Wales from 1992-4. Bacterial isolates, faeces and sera obtained from patients with diarrhoea, bloody diarrhoea and haemolytic uraemic syndrome were examined. Using serotyping, Vero cytotoxin gene probing and serodiagnostic tests for E. coli O157, evidence of infection was detected in 543, 434 and 491 individuals in 1992, 1993 and 1994 respectively; VTEC of serogroup O157 were isolated from 470, 385 and 411 cases. The O157 VTEC strains belonged to at least 19 different phage types (PT) although 84% belonged to PT2, PT49, PT8, PT1 or PT4. Antibodies to E. coli O157 lipopolysaccharide were detected in 13% of the cases. The average annual rate of infection with O157 VTEC was 0.83/100000 and 12% of the 1458 individuals with evidence of infection with VTEC or E. coli O157 developed haemolytic uraemic syndrome. There were at least 18 general outbreaks and many family outbreaks.
Adolescent↗
The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.
Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.
BRCA2 Protein↗
Sequential exposure to estrogen and testosterone (T) and subsequent withdrawal of T increases the level of arginine vasopressin messenger ribonucleic acid in the hypothalamic paraventricular nucleus of the female rat.
The hypothalamic peptides arginine vasopressin (AVP) and oxytocin (OT) have been implicated as mediators of socio-sexual behaviors in addition to their roles in osmolar homeostasis (AVP), milk ejection and uterine contractility (OT). Within 24 h of parturition, OT and AVP messenger ribonucleic acid (mRNA) levels increase in the hypothalamic paraventricular, and to a lesser degree, the supraoptic nucleus (PVN and SON) of the rat. We previously reported that the prepartum increase in OT mRNA is related to the spontaneous decline in progesterone levels prior to parturition. We also reported that increases in PVN and SON OT mRNA can be induced by exposing the ovariectomized rat to a steroid regimen that mimics the steroid milieu of pregnancy, namely sequential estrogen and progesterone and subsequent progesterone withdrawal. Levels of PVN and SON AVP mRNAs were not affected by progesterone withdrawal in late pregnant rats or the steroid regimen that increased OT mRNA in ovariectomized rats. These observations suggest that other factors, perhaps hormonal, may influence AVP mRNA levels. A decline in testosterone coincident with waning progesterone levels also occurs prepartum. Since peak levels of AVP mRNA prepartum coincide with the prepartum decline in testosterone, we questioned whether declining testosterone levels are important for the increase in AVP mRNA levels. To examine a possible role for testosterone in the increased level of AVP mRNA in late pregnancy, we sequentially administered estradiol and testosterone long-term (2 weeks) and removed testosterone 48 h prior to sacrifice. This steroid regimen mimics the estrogen and testosterone pattern of late pregnancy in rats. AVP, but not OT, mRNA levels increased significantly in the PVN of ovariectomized rats receiving this steroid regimen. We also found that implantation of late pregnant rats with testosterone capsules to prevent the spontaneous prepartum decline in testosterone, attenuates the increase in PVN AVP, but not OT, mRNA on day 21 of pregnancy. The data show that sequential estrogen and testosterone and testosterone withdrawal increase the level of PVN AVP mRNA in the female rat.
Animals↗
The prevalence of headache in Greece: correlations to latitude and climatological factors.
A questionnaire study on headaches, using a door-to-door survey, was carried out in a representative sample of the general Greek population, including 1737 men and 1764 women, from 15 to 75 years of age. The parameters evaluated included age, sex, education, socioeconomic status, region of domicile, frequency of headache, use of medication, medical consultation, and family history. Latitude and climatologic factors such as humidity, temperature, and atmospheric pressure were also investigated. Headaches were not classified because the interviewers were not specialists. Nineteen percent of men and 40% of women (mean 29%) suffered from headaches in the prior year. Headaches were more frequent in lower social classes, in people with less education, and in those between 45 and 64 years of age. Nineteen percent of sufferers did not take any medication and 33% used medication every time that they had a headache, while 36% sought medical consultation. Twenty-nine percent of headache sufferers had a family history of headaches. Daily headache was present in 15% of headache sufferers. Humidity and atmospheric pressure were not correlated to headache frequency. However, in the northern areas of Greece, as well as in the regions with low mean temperature, more people suffered from daily headaches. These data may explain the lower 1-year prevalence of headaches in other Greece as compared to the prevalence of headaches in other northern European countries.
Adolescent↗
An epidemiological study of headaches among medical students in Athens.
In order to study the prevalence of frequent headaches among the medical students of Athens University, an epidemiological survey was carried out among 588 medical students (318 men and 270 women), with mean age 23.5 years. Two questionnaires were designed for the study: one general, consisting of 10 questions and a second one, specific for headache sufferers, consisting of 117 questions. All those with headache who voluntarily completed the two questionnaires also underwent a neurological examination. Thirty point eight percent of men and 50.3% of women reported various headache attacks during the previous 6 months (39.6% in both sexes). However, only the 11.9% of students (from both sexes) reported that they suffered from disturbing headaches. The 6-month prevalence of migraine was 2.4% and 9.5% for tension-type headache (in both sexes). Cluster headache was not traced. The prevalence of nonclassifiable headaches (according to the criteria of the International Headache Society) was 0.85%. Headache was correlated to sex (more frequent among women) and anxiety level (Hamilton scale for anxiety). Headache prevalence was not correlated to smoking and social class.
Adult↗
Endometrial thickness: individual and mean growth profiles for different hormone replacement regimens.
Currently, there is a paucity of data describing endometrial growth, with most studies concentrating on endometrial thickness immediately prior to implantation or embryo transfer. This study looked at the individual and combined growth profiles of 67 volunteers receiving three different hormone replacement regimens. Each treatment regimen was in excess of that considered necessary for optimal growth, and all promoted an endometrial thickness that would be considered satisfactory for embryo transfer. Three patterns of growth were identified, but overall there was a decrease in the rate of endometrial growth with duration of treatment. As expected, analysis of variance did not show a significant difference between the mean growth profiles for the three hormone replacement regimens. The correlation (r = 0.45, P < 0.0001) between rank order on day 3 and day 10 of treatment indicates that interim analysis during early treatment cannot accurately predict later thickness, but a doubling of endometrial thickness can be expected in most cases. A relationship between endometrial thickness and either the treatment dose or serum concentrations of oestradiol was not found. These findings suggest that manipulation of endometrial growth is not possible by adjustment of either the treatment dose or serum concentration. The findings indicate that treatment beyond 12 days does not promote either a clinically significant increase in endometrial thickness of an excessive thickness, suggesting that maintenance of an oocyte recipient in a pseudo-follicular phase is unlikely to be disadvantageous to implantation.
Adult↗
Small-bowel obstruction caused by tuberculous strictures in an infant.
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Child↗