Cow's Milk Exposure and Asthma in a Newborn Cohort: Repeated Ascertainment Indicates Reverse Causation

The effect of cow's milk consumption on childhood asthma has been debated for several years. This study attempts to provide further insight into this association through the use of a longitudinal study design. Newborns from parents with atopic history were recruited from Germany, Austria, and England (n = 696). For five repeated ascertainments, information was collected on cow's milk exposure, incidence of doctor-diagnosed asthma, and confounders. Generalized estimation equations, incorporating different models (concurrent, delayed, combined, and reverse causation), were used to determine this association. No association between cow's milk consumption and childhood asthma was found for the concurrent effects model (OR = 0.81, 95% confidence interval [CI]: 0.55, 1.20). In the delayed effects model, the direction of the association varied with time of follow-up. Thus, we stratified by period, which resulted in a significant protective delayed effect at 36 months (OR = 0.18, 95% CI = 0.06, 0.49). However, reverse causation negated this finding since the presence of asthma in prior months led to a reduction in further exposure to cow's milk (OR = 0.40, 95% CI = 0.16, 0.99). Hence, cow's milk consumption does not protect against childhood asthma. The apparent protection of cow's milk against asthma may result from parents of asthmatic children avoiding cow's milk, rather than actual prophylaxis.     

KY-62, a Polyene Analog of Amphotericin B, for Treatment of Murine Candidiasis

KY-62 is a water-soluble analog of amphotericin B. In vitro testing of five clinical isolates of Candida albicans showed KY-62 to have potency similar to that of amphotericin B. KY-62 was administered to mice infected intravenously with C. albicans. In vivo, KY-62 was effective in immunocompetent mice, with potency similar to that of amphotericin B. KY-62 was well tolerated up to 30 mg/kg of body weight per dose, an amount that would be lethal with amphotericin B. KY-62 was less effective in mice rendered neutropenic with 5-fluorouracil. The addition of flucytosine had little effect. KY-62 may have potential for clinical development.     

The response to carbogen breathing in experimental tumour models monitored by gradient-recalled echo magnetic resonance imaging.

Gradient-recalled echo magnetic resonance imaging (GRE MRI), which gives information on blood flow and oxygenation changes (Robinson SP, Howe FA, Griffiths JR 1995, Int J Radiat Oncol Biol Phys 33: 855), was used to observe the responses of six rodent tumour models to carbogen breathing. In one transplanted rat tumour, the Morris hepatoma 9618a, and a chemically induced rat tumour, the MNU-induced mammary adenocarcinoma, there were marked image intensity increases, similar to those previously observed in the rat GH3 prolactinoma. In contrast, the rat Walker carcinosarcoma showed no response. In two mouse tumours, the RIF-1 fibrosarcoma and the human xenograft HT29, carbogen breathing induced a transient fall in signal intensity that reversed spontaneously within a few minutes. The rat GH3 prolactinoma was xenografted into nude mice, and an increase in image intensity was found in response to carbogen, suggesting that any effects that carbogen may have had on the host were not significant determinants of the tumour response. The increases in GRE image intensity of the MNU, H9618a and GH3 tumours during carbogen breathing are consistent with increases in tumour oxygenation and blood flow, whereas the responses of the RIF-1 and HT29 tumours may be the result of a transient steal effect followed by homeostatic correction.     

An adjusted version of Kohlberg's moral theory: discussion of its validity for research in nursing ethics

Critics of Kohlberg's moral theory today focus on the content of his theory and more specifically on its justice-orientated moral concept. This has led to the well-known 'justice-care debate'. The purpose of this article is to critically examine the validity of Kohlberg's moral theory for research in nursing ethics from a caring perspective (referring to the content) as well as from a cognitive-structural perspective (referring to the basic assumptions of the model). The analysis points to the usefulness and value of the cognitive-structural model to empirically study nurses' ethical behaviour; the content of Kohlberg's model, however, needs to be adapted by adding a caring perspective as well as some personal and situational variables. An adjusted version of Kohlberg's model is proposed and discussed.     

Patch clamp studies on the kinetics and selectivity of N-methyl-d-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan)

Memantine (1-amino-3,5-dimethyladamantan) was tested as an antagonist of N-methyl-d-aspartate (NMDA) receptors on cultured superior collicular and hippocampal neurones using the patch clamp technique and its actions were compared to those of Mg²⁺ ions, ketamine, dextrorphan, dextromethorphan, phencyclidine and dizocilpine (MK-801). Memantine (2–33 μM) concentration-dependently antagonized responses to NMDA 100 μM with an IC₅₀ of 2.92 ± 0.05 μM. In contrast, current responses to (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (l-AMPA 50–100 μM) and γ-amino butyric acid (GABA 10 μM) were unaffected by Memantine 8 μM. Memantine 8 μM caused a non-parallel shift of the NMDA concentration-response curve to the right in a manner indicative of uncompetitive open channel block. The effects of memantine were similar to ketamine in that both antagonists were weakly use- and strongly voltage-dependent. In contrast, MK-801, phencyclidine and dextrorphan showed much slower kinetics that was reflected in their marked use- and weaker voltage-dependency. The antagonistic effects of memantine were not reversed by increasing concentrations of glycine (0.1–100 μM) ruling out the possibility of an interaction of memantine with the strychnine-insensitive glycine modulatory site associated with the NMDA receptor-channel complex. Memantine (1–100 μM) also selectively antagonized responses to NMDA (40 μM) in the cortical wedge preparation with IC₅₀ of 12.9 ± 1.5 μM.     

Does the health status of chronically ill patients predict their judgements of the quality of general practice care?

Patients' health status as well as patients' judgements of care are used for assessing patients' perspectives, but the relation between those two concepts is unclear. In this study we explored whether health status predicts patients' judgements of the quality of general practice care. Hand-distributed and mailed surveys were performed by 28 general practitioners in The Netherlands. Chronically ill patients were approached when visiting the general practice or drawn from the practice registers. Health status was measured by WONCA/COOP charts, and patients' judgements by the CEP, a previously validated questionnaire. The response rate was 63% (n=762). When controlled for other patient characteristics, a poor overall health predicted less positive judgements of medical care, information, counselling, relation and communication, continuity of care and the organization of appointments (p[lessthan]0.01). Poor mental well-being predicted less positive judgements of the cooperation between care providers and a stronger need for more care (p[lessthan]0.001). The four other aspects of health status did not predict the patients' judgements. Judgements about the premises and the availability for emergencies were not predicted by health status. It can be concluded that a multidimensional approach should be used for interpreting the relations between patients' health status and their judgements of general practice care.     

Genotypic selection of mutated DNA sequences using mismatch cleavage analysis, a possible basis for novel mutation assays

A novel technique for the selection of mutated DNA sequences,termed mismatch cleavage-polymerase chain reaction (MC-PCR),is proposed. The method is based on hybridizing genomic DNAwith a suitable probe, several 100 bp long. Mutated DNA sequenceswill form mismatched heteroduplexes which are cleaved by usingresolvases. Cleaved heteroduplexes are detected by ligationto an oligonucleotide adaptor and then amplified by using PCR.If practical, this technique would have considerable advantagesover the restriction site mutation (RSM) method. Failure toachieve cleavage efficiencies of close to 100% will not compromisesuccess. This is because positive signals (PCR amplification)arise from cleaved mutated sites and not, as in RSM, from DNAsequences resistant to cleavage by restriction endonucleases.Furthermore, the mutational target is much larger than in RSM.It would be possible to screen stretches of DNA several 100bp in length for mutations. Any mutation, independent of itslocation, could be identified. The usefulness of MC-PCR forthe genotypic selection of mutants will depend on the effectivenesswith which a small number of mismatched heteroduplexes can berecognized, cleaved and ligated. ¹To whom correspondence should be addressed