Accommodation and visual acuity were measured in 53 children with Down's syndrome aged between 12 weeks and 57 months. Results were compared with data for 136 control (typically developing) children aged between 4 weeks and 48 months. Whereas the control children accommodated accurately on near targets, accommodation was defective in 92% of the children with Down's syndrome, and there was no change in accommodative ability with age. On the other hand, visual acuity lay within normal limits for the younger children. Children over the age of 2 years showed a below-normal visual acuity, which is not explained either by refractive error or by the effect of poor accommodation. The data suggest a sudden change in the rate of development of visual acuity which may be associated with physiological changes in the visual cortex. Previously reported defects of accommodation and visual acuity in older children and adults with Down's syndrome are confirmed by our findings in infants and young children.

Accommodation, Ocular↗

PubMed1996

Suicide and attempted suicide occur in the context of terminal and severe medical illness.

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Humans↗

PubMed1995

Circadian variation in human ventricular refractoriness.

BACKGROUND: The incidence of sudden cardiac death is highest in the morning hours. Although a circadian variation in myocardial ischemia may be responsible in part for this observation, other factors also may be contributory. It is not known whether a circadian variation in ventricular refractoriness exists that may be related to the increased morning incidence of sudden cardiac death. METHODS AND RESULTS: Nine subjects with primary conduction system disease, no evidence of structural heart disease, and permanent pacemakers were studied. Autonomic nervous system function as assessed by tilt table and baroreflex sensitivity testing was normal in all subjects. Using noninvasive programmed stimulation, ventricular effective refractory periods were measured hourly for 24 hours. Potassium, epinephrine, and norepinephrine levels also were measured hourly. In a subset of five subjects, ventricular refractory periods were again measured hourly over 24 hours during beta-blockade. A significant circadian variation in ventricular refractoriness was noted, with a mean difference between the shortest and longest refractory periods in individual subjects of 23 ms and 21 ms at drive cycle lengths of 600 ms and 400 ms, respectively. In eight subjects, the shortest refractory periods observed over 24 hours occurred within 2 hours of waking (random probability < 10(-8)). Adjustment of refractory period data according to the hour of waking resulted in a better correlation between ventricular refractory periods and time. Although a significant circadian variation was observed in potassium and catecholamine levels, neither was an independent predictor of refractory periods after adjustment for the hour of waking. The adjusted time of day was the only significant (P < .0001) independent predictor of refractory periods. beta-Blockade abolished the circadian variation in ventricular refractory periods. CONCLUSIONS: A significant circadian variation in ventricular refractory periods exists. Maximal shortening between hourly refractory periods as well as the shortest refractory periods occur in the early morning hours when the incidence of sudden cardiac death is greatest. Fluctuations in beta-adrenergic tone appear to be largely responsible for this phenomenon.

Adult↗

PubMed1995

The euthanasia controversy. Decision-making in extreme cases.

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Adult↗

PubMed1995

Comparison of an oral rice-based electrolyte solution and a glucose-based electrolyte solution in hospitalized infants with diarrheal dehydration.

This randomized trial compared the efficacy of a rice-based (50 g/L) oral rehydration solution with the standard glucose-based WHO/UNICEF solution in the treatment of 100 hospitalized infants, ages 3-18 months, with acute dehydrating diarrhea. The main outcomes examined were stool output and duration of diarrhea. Patients were placed on a "metabolic" bed so that intake and losses could be measured accurately throughout the study. Overall, 89% of patients were successfully rehydrated orally; the rehydration failure rate was similar in the two groups and it was significantly associated with infection by specific E. coli serotypes. Stool output in the first 24 h was 11% lower in the rice group (112 versus 126 ml/kg), but this difference was not significant. Neither stool output in the second 24 h nor total stool output were different between groups. The median duration of diarrhea was 3.8 days in the rice group and 3.9 days in the glucose group (p = NS). Other (secondary) outcomes, such as fluid intake, urine output, emesis losses, weight change, and electrolyte balance were also similar between the two groups. Some evidence of carbohydrate malabsorption was detected in 61% of the rice group versus 45% of the glucose group (p = NS) and was not associated with any particular treatment outcome. These results show that a rice-based oral rehydration solution is as efficacious as, but not better than the standard glucose-based solution in the treatment of infants with acute dehydrating diarrhea not associated with cholera.

Acute Disease↗

PubMed1995

Autonomy, problem-based learning, and the teaching of medical ethics.

Autonomy has been the central principle underpinning changes which have affected the practice of medicine in recent years. Medical education is undergoing changes as well, many of which are underpinned, at least implicitly, by increasing concern for autonomy. Some universities have embarked on graduate courses which utilize problem-based learning (PBL) techniques to teach all areas, including medical ethics. I argue that PBL is a desirable method for teaching and learning in medical ethics. It is desirable because the nature of ethical enquiry is highly compatible with the learning processes which characterize PBL. But it is also desirable because it should help keep open the question of what autonomy really is, and how it should operate within the sphere of medical practice and medical education.

Curriculum↗

PubMed1995

Use of adventure experiences in traditional counseling interventions.

Use of adventure as an intervention in traditional counseling was explored with 84 adolescent clients from two community-based counseling agencies and residents from two boys' homes. The adolescents were assigned to conditions of counseling plus adventure experiences, counseling only, adventure only, or a control. Analysis indicated limited support for increasing self-esteem and social skills by adding adventure experiences to on-going counseling.

Adolescent↗

PubMed1995

It's not just nursing anymore....

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California↗

PubMed1994

T lymphocyte T cell-B cell-activating molecule/CD40-L molecules induce normal B cells or chronic lymphocytic leukemia B cells to express CD80 (B7/BB-1) and enhance their costimulatory activity.

Activation-induced cell surface molecules are involved in mediating bidirectional T-B lymphocyte signaling that is important in the induction of T or B lymphocyte effector functions. In this regard, T-BAM/CD40-L is an activation-induced CD4+ T cell surface molecule known to be important in inducing B cell effector functions. This report demonstrates that T-BAM/CD40-L molecules on a Jurkat T cell leukemia subclone (D1.1) or nonlymphoid 293 kidney cell transfectants induce B cells or B-CLL cells to express CD80 (B7/BB-1) in a manner that is specifically inhibited by anti-T-BAM/CD40-L mAb 5C8. Because activation-induced B cell surface molecules, such as CD80, deliver costimulatory signals to T cells that augment T cell proliferation, the functional costimulatory capacity of T-BAM/CD40-L-primed B cells and B-CLL cells was studied. T-BAM/CD40-L-primed B cells or B-CLL cells augment the proliferative responses of allogenic T cells. Furthermore, T-BAM/CD40-L priming is specifically inhibited by mAb 5C8. Together, these studies demonstrate that T-BAM/CD40-L induces CD80 expression on resting B cells or B-CLL cells. Moreover, T-BAM/CD40-L signaling enhances B cell costimulatory capacity. These studies suggest that T-BAM/CD40-L molecules not only induce B cell differentiative processes that result in Ab secretion, but also enable B cells to prime Ag-specific T cells for subsequent clonal expansion.

B-Lymphocytes↗

PubMed1994

The cytolytic toxin aerolysin: from the soluble form to the transmembrane channel.

Aerolysin is a cytolytic toxin which forms channels in the plasma membranes of eucaryotic cells. The protein is secreted by Aeromonas hydrophila as an inactive protoxin. Its stability and water solubility are conferred by its ability to dimerize. Maturation of the protein occurs through proteolytic removal of a C-terminal peptide outside the secreting cell. Although the aerolysin which is so produced is still a dimer, it then has the ability to oligomerize. The oligomer is the active form of the toxin, capable of forming the transmembrane channels that disrupt cells. We review here the present knowledge about the structure of aerolysin in relation to the various steps in channel formation.

Aeromonas hydrophila↗

PubMed1994

The effects of coumarin and suramin on the growth of malignant renal and prostatic cell lines.

Coumarin is known to exert an anti-neoplastic action in patients with malignant melanoma and renal cell carcinoma. We examined the effects of various concentrations (0, 10, 50, 100, 250, 500 micrograms/ml) of coumarin on the proliferation of two renal cell carcinoma cell lines (786-O and A-498) and two malignant prostatic cell lines (DU145 and LNCaP). After 5 days of treatment, coumarin inhibited the growth of the four cell lines. The LNCaP prostatic cell line was more sensitive than the other cell lines to the inhibitory effects of coumarin. We also examined the effects of various concentrations of suramin (0, 50, 200 and 400 micrograms/ml), and anti-neoplastic compound currently undergoing clinical trials, on the growth of the 786-O and LNCaP cell lines. Both of these were inhibited by suramin at concentrations greater than 100 micrograms/ml. Finally we examined the effects of combined treatment with coumarin and suramin on the growth of LNCaP and 786-O cells. When combined with all concentrations of suramin studied (0, 50, 200 and 400 micrograms/ml), coumarin further inhibited cellular proliferation of the LNCaP and 786-O cell lines. However, the combination of the highest concentration of coumarin (500 micrograms/ml) with suramin at 400 micrograms/ml did not inhibit the proliferation of the cells more than 500 micrograms/ml coumarin alone.

Carcinoma, Renal Cell↗

PubMed1994

Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: identity with the CD40-ligand.

"T-cell B-cell Activating Molecule" (T-BAM) is an activation-induced surface protein on CD4+ T cells that mediates a contact-dependent signal for B cell differentiation and immunoglobulin (Ig) secretion. The T-BAM protein on a helper clone of Jurkat (D1.1) was affinity purified using the anti-T-BAM mAb, 5c8. The NH2-terminal amino acid sequence of purified T-BAM was determined and found to be highly homologous to the predicted NH2-terminal sequence of a T cell ligand to the B cell CD40 molecule (CD40-L). From a D1.1 cDNA library, a clone was isolated that encodes CD40-L by sequence and drives expression of T-BAM protein on transfected cells, demonstrating that the T-BAM and CD40-L genes and proteins are identical. Moreover, transfection of T-BAM was shown to confer to non-lymphoid cells, the ability to induce B cells to upregulate the expression of surface CD23 molecules. In previous studies we showed that T-BAM was expressed predominantly on activated CD4+ and on few if any CD8+ cells. Although the current work confirms that T-BAM is largely restricted to activated CD4+ T cells, we now provide definitive evidence that T-BAM can be expressed by a small population of CD8+ T cells after activation. Importantly, a subset of CD8+ T cells do not express T-BAM after activation and this T-BAM- phenotype is maintained on certain CD8+ T cell clones. Taken together, these data unify the biology and structure of T-BAM and CD40-L and this synthesis has implications for understanding the T cell regulation of the humoral immune response.

Amino Acid Sequence↗

PubMed1994

Mortality after spinal and general anaesthesia for surgical fixation of hip fractures.

One thousand, three hundred and thirty three patients who underwent anaesthesia for surgical fixation of a hip fracture were studied prospectively to assess the effects on outcome of general and spinal anaesthesia. There were no significant differences between the groups in risk factors, length of hospital stay or mortality rates after 30 days or one year. The data presented may be useful for those wishing to audit anaesthetic services provided to patients with hip fracture.

Aged↗

PubMed1994

Gastrointestinal symptoms and diet of members of an irritable bowel self-help group.

A self-administered questionnaire was completed by 103 members of a self-help group for irritable bowel syndrome (IBS) and 130 controls, to compare the presence of IBS symptoms. Dietary fibre prescription, compliance and efficacy were documented in the IBS group. There were significant differences in the frequency of defaecation and number of symptoms present between the two groups. Most of the IBS subjects had been prescribed a high fibre diet but adherence to the diet and symptomatic improvement were poor. In contrast many IBS sufferers were following a range of diets not prescribed by their doctor. The seriousness of the IBS condition was highlighted by the fact that 8% of the IBS group had retired early due to their condition.

Adult↗