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Biomedical subjects

D Allen

Publications and source records attributed to D Allen.

At least 73 records · Page 4Linked to original sources

Rapid separation of CD4+ and CD19+ lymphocyte populations from human peripheral blood by a magnetic activated cell sorter (MACS).

Rapid purification of human lymphocyte subpopulations is an essential step in order to elucidate their interactions and/or contributions in various disease states. Cell purification using a Magnetic Activated Cell Sorter (MACS) is a relatively new technology which has been shown to be rapid and yield highly purified populations of cells. This report describes both a simple one-step positive selection method using the MACS to purify either human CD4+ or CD19+ lymphocytes from PBMC and a sequential separation of both CD4+ and CD19+ cell populations. These methods can separate the cell populations in approximately 4 h with yields > 90% and purity of 97 +/- 3% for CD4+ T cells and 92 +/- 5% for CD19+ B cells. In functional studies, purified CD19+ B cells secreted 13- and 24-fold more IgM and IgG, respectively, than the CD19- cell fraction in 10 day B cell stimulation assays. Purification of the two cell types did not cause any significant activation as shown by proliferation. Both cell types, however, were able to proliferate upon stimulation with interleukin-2.

Antigens, CD

The effects of single doses of CL284,846, lorazepam, and placebo on psychomotor and memory function in normal male volunteers.

The effects of single doses of CL284,846 (20 mg), lorazepam (2 mg) and placebo on psychomotor performance, memory function and subjective feelings were assessed in 12 normal, healthy male volunteers. Each subject received each treatment in balanced order and a minimum of 6 days was left between treatments. The subjects performance on a comprehensive battery of tests of psychomotor performance, memory function and subjective ratings was assessed pre-treatment and at 1, 3 and 5 h post-treatment. In general, the effects of CL284,846 on memory were similar to those of lorazepam at 1 h post-treatment but, recovery was rapid with CL284,846. Impairments induced by lorazepam persisted throughout the post-drug testing sessions. This pattern of effects was repeated across most of the variables tested. However, at 1 h, CL284,846 produced less marked psychomotor impairment than lorazepam. The results of this study suggest that CL284,846 is a safe, rapid acting and effective sedative with some clear advantages over lorazepam with respect to unwanted cognitive and psychomotor impairments.

Acetamides

Effects of lorazepam upon recollective experience in recognition memory.

The effects of lorazepam (2 mg) and placebo upon recognition memory with and without conscious recollection were assessed in a cross-over study with normal volunteers. When recognising a word from study lists presented before and 1, 3 and 5 h after drug administration, subjects were required to indicate whether they could consciously recollect the word's prior occurrence or recognised it on the basis of "knowing"; in the absence of conscious recollection. Lorazepam only impaired word recognition which was accompanied by conscious recollection, and further, the level of this impairment correlated significantly with each of three different indices of subjects' arousal at the time of presentation of each list. Recognition in the absence of conscious recollection was not impaired but somewhat heightened by lorazepam, and these effects did not significantly relate to any index of arousal. These findings are interpreted as providing further support for the notion that recognition entails two distinct components, one based on contextual and associative information and related to conscious recollection, the other possibly based on a "traceless" perceptual or semantic memory system and related to feelings of knowing in the absence of conscious recollection. Implications are drawn for a contextual-encoding/retrieval account of lorazepam-induced amnesia.

Adult

Does chromatic sensitivity develop more slowly than luminance sensitivity?

Chromatic sensitivity is very low in humans during the first few months of life. We examined whether low chromatic sensitivity reflects a deficiency among chromatic mechanisms or whether it is simply a manifestation of poor visual sensitivity in general. The sweep VEP was used to measure contrast sensitivity to gratings varying in the mixture of red and green components. For infants from 2 to 8 weeks of age, sensitivity to all mixtures was lower than color-normal adults' sensitivity, but infant and adult ratios of luminance/chromatic sensitivity were similar. This finding is consistent with the hypothesis that infants have functional MWS and LWS cones and the requisite post-receptor chromatic mechanisms to compare their signals.

Age Factors

Alstonia species: are they effective in malaria treatment?

A review of the literature on Alstonia species indicates that evidence in support of their effectiveness in the treatment of malaria is controversial. The antiprotozoal activity of the major alkaloid present in Alstonia species, echitamine, was assessed in vitro against Plasmodium falciparum and Giardia intestinalis. Echitamine displayed little antiplasmodial activity, but two quinoline alkaloids from A. coriacea (corialstonine and corialstonidine) were found to have some activity against P. falciparum although this was approximately 10 times less than that of quinine. None of the three Alstonia alkaloids was active against G. intestinalis. These results are discussed in the context of previously published data.

Alkaloids

Silastic catheterization of the axillary vein in neonates: an alternative to the internal jugular vein.

The axillary vein is a suitable alternative to the jugular venous system for tunnelled silastic catheterization in neonates, and should be included in the armamentarium of the surgeon who treats neonates. It is technically easy and is comparable to the internal jugular vein in terms of complications. Proper positioning of the catheter tip can sometimes be problematic, but without a resultant increase in morbidity or mortality.

Axillary Vein

Developing a restraint use policy for acute care.

Restraint use has been a recent focus of attention in long-term care facilities. The Joint Commission on Accreditation of Healthcare Organizations, the Commission on Accreditation of Rehabilitation Facilities, and the Food and Drug Administration have devoted attention to the prudent use of restraints. The authors address efforts of an acute care facility to comply with these regulations.

Aged

Early events in immune evasion by the lentivirus maedi-visna occurring within infected lymphoid tissue.

Infections caused by lentiviruses, including human immunodeficiency virus, are characterized by slowly progressive disease in the presence of a virus-specific immune response. The earliest events in the virus-host interaction are likely to be important in determining disease establishment and progression, and the kinetics of these early events following lentiviral infection are described here. Lymphatic cannulation in the sheep has been used to monitor both the virus and the immune response in efferent lymph after infection of the node with maedi-visna virus (MVV). Viral replication and dissemination could be detected and consisted of a wave of MVV-infected cells leaving the node around 9 to 18 days postinfection. No cell-free virus was recovered despite the fact that soluble MVV p25 was detected in lymph plasma. The maximum frequency of MVV-infected cells was only 11 in 10(6) but over the first 20 days of infection amounted to greater than 10(4) virus-infected cells leaving the node. There was a profound increase in the output of activated lymphoblast from the lymph nodes of infected sheep, characterized by an increased percentage of CD8+ lymphoblasts. All of the CD8+ lymphoblasts at the peak of the response expressed both major histocompatibility complex class II DR and DQ molecules but not interleukin-2 receptor (CD25). The in vitro proliferative response of efferent lymph cells existing the node after challenge with MVV to both recombinant human interleukin-2 and the mitogen concanavalin A was decreased between days 8 and 16 postinfection, and a specific proliferative response to MVV was not detected until after day 15. Despite the high level of CD8+ lymphoblasts in efferent lymph, direct MVV-specific cytotoxic activity was demonstrated in only one of the five MVV-challenged sheep. MVV-specific antibody responses, including neutralization and MVV p25 immune complexes in efferent lymph, were detectable during the major period of virus dissemination. The relationship of these findings to the evasion of the host's acute immune response by MVV is discussed.

Animals

Public perceptions of the funding of NHS dental services.

A survey was carried out of 102 members of the general public, asking for their views of the recent changes in the government funding of NHS dentistry. Approximately 80% of those surveyed had heard about the changes. The majority thought that the implications of the change would be a rise in costs to patients and a fall in the number of NHS dentists.

Adolescent

Septic metritis secondary to torsion of a pedunculated uterine fibroleiomyoma in a filly.

A 2-year-old Arabian filly was referred for evaluation of a serosanguineous vaginal discharge. Palpation per rectum revealed a large, fluid-filled uterus and a uterine mass. The filly developed septic metritis and secondary laminitis as a result of torsion and necrosis of a pedunculated uterine mass. Ovariohysterectomy was performed. The entire cervix was removed with the uterus. Gross examination of the excised uterus revealed 3 intraluminal masses. Histologic evaluation identified the tumors as fibroleiomyoma. The filly recovered completely, and there was no recurrence of the tumor.

Animals

Area postrema mediation of physiological and behavioral effects of lithium chloride in the rat.

The area postrema (AP), a chemoreceptor trigger zone for nausea and vomiting, has been implicated in taste aversion conditioning with LiCl. In addition to taste aversion acquisition, the present studies indicate that a number of other responses to LiCl administration are eliminated by lesions of the AP. These include a behavioral response, 'lying-on-belly' as well as two physiological responses, delayed stomach emptying and hypothermia. These findings suggest that the area postrema is critically involved in the detection of LiCl and in a wide range of responses to this toxin. They also provide strong evidence that the failure to acquire conditioned taste aversions to LiCl-paired flavors after AP lesions can be attributed to the absence of a significant 'illness' response in lesioned animals.

Animals

The interactions of ethanol with single and repeated doses of suriclone and diazepam on physiological and psychomotor functions in normal subjects.

The effects of diazepam (5 mg t.i.d.), suriclone (0.2 and 0.4 mg t.i.d.) and placebo (t.i.d.) were assessed in 12 normal, healthy volunteer subjects after a single dose and after treatment for a period of 8 days. A battery of physiological, psychomotor and subjective tests was administered on days 1 and 8 both before and after drug and after a measured dose of ethanol. The effects of diazepam on the EEG were characteristic of benzodiazepines-a decrease in the slow frequency wave-bands, an increase in fast frequency wave-band and diminished evoked response amplitude. Suriclone had similar effects on fast frequency activity and evoked response amplitude but, in contrast to diazepam, also increased the slow frequency wave-bands after 7 days treatment. Some improvements in performance were seen with suriclone on critical flicker fusion, tapping speed, spiral maze and digit cancellation. In contrast, suriclone impaired performance to a greater extent than diazepam on digit symbol substitution and symbol copying. Body sway was also enhanced by suriclone to a greater extent than diazepam. Subjective ratings for mood and adverse-effects showed few differences between suriclone or diazepam. However, suriclone caused greater gastro-intestinal disturbances than diazepam, especially after ethanol, and subjects rated themselves as more antagonistic and more irritable on suriclone. Ratings for calmness suggested that in contrast to diazepam, suriclone had no anxiolytic effect. Several of the parameters tested showed a build up of effect with diazepam over the treatment period which was not seen with suriclone. It is suggested that this difference may be due to differences in elimination rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Is the visual field temporally homogeneous?

We asked the question "is the visual field temporally homogeneous when the well known spatial inhomogeneity is taken into account?" Our results show that the visual field exhibits inhomogeneity for stimuli of low spatial frequency for which the spatial inhomogeneity is minimal. This inhomogeneity takes the form of a reduction in sensitivity for stimuli of low temporal frequency in the periphery and an enhancement of sensitivity for stimuli of high temporal frequency in the periphery. The low temporal frequency loss in the periphery is post-receptoral and must involve a selective loss of sensitivity of the low pass filter. The enhanced high frequency sensitivity may be post-receptoral or purely receptoral. The consequence of such an inhomogeneity for subsequent stages of visual processing is discussed.

Adult

The effects of luminance on FPL and VEP acuity in human infants.

Grating acuity was measured in 16-week-old human infants. Three measurement techniques were used: forced-choice preferential-looking (FPL), and two visual-evoked-potential (VEP) techniques. The stimuli were counterphase flickering sinewave gratings with a space-average luminance of -1.0 or 2.0 log cd/m2. Slightly different luminance-dependent changes occur between FPL and VEP acuities, suggesting that some factor influences the two methods differently as stimulus luminance varies. A comparison between FPL acuities and VEP acuities within infants suggests a quantitative relationship between techniques. Infant's acuity for sinewave gratings with a space-average luminance of -2.0, -1.0, 0.0, 1.0 and 2.0 log cd/m2 was also measured using a single VEP paradigm. The results are compared to the same measurements in adults and to infant and adult ideal observers. VEP acuity in this group of infants improves by about 0.5 log units between -2.0 and 0.0 log cd/m2 and remains asymptotic between 0.0 and 2.0 log cd/m2. This result suggests that luminance-dependent changes in infant acuity cannot be fully accounted for by immaturities in the optics and photoreceptor spacing and efficiency.

Evoked Potentials, Visual

Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990.

From 1984-1990, 143 patients with squamous cell or adenocarcinoma of the esophagus were enrolled in a Phase I/II study of neoadjuvant chemotherapy followed by concurrent chemotherapy plus radiotherapy with or without subsequent esophagectomy. Patients received one cycle of Cisplatin or Carboplatin plus Etoposide for squamous cell carcinoma, or Cisplatin or Carboplatin plus 5FU for adenocarcinoma, followed by two cycles of the same chemotherapy given concurrently with 44-46 Gy over 5 weeks. Operable patients then underwent esophagectomy. Inoperable patients and those with positive surgical margins received additional irradiation (16-18 Gy). Twelve percent of the surgical group received preoperative radiotherapy doses > or = 50 Gy. Seventy-two percent (103) had clinical Stage I-III tumors and 28% (40) were clinical Stage IV (1983 American Joint Committee on Cancer criteria). Only clinical Stage I-III patients were analyzed with respect to patterns of failure. Isolated local failure occurred in 19/103 (18%) of clinical Stage I-III patients. Both local and distant relapse occurred in 15/103 (15%), and distant metastases alone occurred in 25/103 (24%). The 3-year actuarial rates of local and distant failures were 45% and 60%, respectively. Among the clinical Stage I-III patients who underwent surgery (n = 58) versus those who did not (n = 45), the 3-year actuarial local and distant failure rates were 30% versus 60% and 45% versus 45%, respectively. Multivariate analysis was performed to identify significant predictors of local control. For all clinical Stage I-III patients, treatment with surgery (p = 0.001) and with three or more cycles of chemotherapy (p = 0.02) were significant predictors of improved local control. Patients who underwent surgery were significantly younger and had a better performance status than those who did not. The improvement in local control with surgery did not translate into better survival, likely on account of a high operative mortality rate in older patients and those receiving > or = 50 Gy preoperatively. We conclude that local control remains poor with concurrent chemotherapy + radiotherapy for esophageal cancer. The addition of surgery improved local control, but distant metastases remain a problem both in this group of patients as well as those treated without esophagectomy. Efforts to improve local control appear warranted, but it remains to be demonstrated that improved local control translates into improved survival in esophageal cancer because of a high rate of distant metastases in patients whose disease is controlled in the esophagus.

Adenocarcinoma

Long term effects of tamoxifen. Biological effects of Tamoxifen Working Party.

A total of 153 breast cancer patients who participated in two trials of adjuvant tamoxifen and who had not recurred were recruited into a study of the long term effects of tamoxifen. There were 60 controls (no tamoxifen), 73 ex-users (mostly for 2 years) and 20 current users (median treatment duration 72 months) and the median follow-up time was 7 years. A wide ranging study of lipids, hormones, bone density and haemostasis was undertaken. When compared with controls, current users had lower cholesterol levels (especially low density cholesterol), and increased triglyceride levels. Thyroid hormones were higher and sex hormone binding globulin was almost doubled. Bone density was non-significantly higher, clotting times were slightly shorter and fibrinogen and antithrombin III levels were reduced. However few of these changes persisted in ex-users, suggesting that most of the biological effects of treatment are reversible on cessation of treatment. This is reassuring for potentially negative side-effects, but also indicates that potentially positive 'side-effects' such as cholesterol lowering only occur while on active treatment.

Bone Density