Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium.

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. Transgenic and control males were injected with cadmium, and the histology of the testes was examined. An injection of 7.5 mumol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 mumol Cd/kg caused rapid changes in the histology of the testes and resulted in pronounced testicular necrosis in both control and transgenic mice. Female transgenic and control mice were mated and then injected with cadmium (30-45 mumol Cd/kg) on the day of blastocyst implantation (day 4). In both of these groups, injection of cadmium reduced pregnancy rate, and no dramatic protection was afforded by maternal and/or embryonic overexpression of MT. Thus, overexpression of MT-I does not significantly protect against either of these cadmium-induced effects on fertility.     

Pharmacokinetics and Inflammatory Fluid Penetration of Clinafloxacin

A single 200-mg dose of clinafloxacin was given orally to each of nine healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharidin-induced inflammatory fluid, and urine over the following 24 h (48 h in the case of urine). The mean maximum concentration in plasma was 1.34 μg/ml at a mean time of 1.8 h postdose. The mean maximum concentration in the inflammatory fluid was 1.3 μg/ml at 3.8 h postdose. The mean elimination half-life of clinafloxacin in plasma was 5.65 h. The overall penetration into the inflammatory fluid was 93.1%, as assessed by determining the ratio of area under the concentration-time curves. Recovery of clinafloxacin in urine was 58.8% by 24 h and 71.8% by 48 h postdose.     

The implications of Project 2000 and the formation of links with higher education for the professional and academic needs of nurse teachers in the United Kingdom

A national study was conducted between 1991 and 1994 to explore and describe the changing role of the nurse teacher following the introduction of Project 2000 pre-registration nursing courses. Multiple methods were used to collect data from a wide variety of respondents (nurse teachers, midwife teachers, clinical nurses, health service managers and higher education lecturers). This paper presents the findings relating to the impact of Project 2000 and the move into higher education on the continuing educational needs of nurse teachers. Views on college strategies for staff development, the changing nature of teachers'academic and professional development needs and the problems of the conflicting demands experienced are reported. The research highlights the need for clinical credibility to be clearly defined in relation to nurse teachers and for educational institutions to place more emphasis on teachers'clinical development if the rhetoric of policy is to become a reality.     

Consequences of misfilling contemporary vaporizers with desflurane

Desflurane is a volatile anaesthetic that combines low blood gas solubility (blood/gas partition coefficient =0.42 at 37° C), moderate potency (MAC = 6–7%), and high volatility (vapour pressure =681 mmHg at 20° C, boiling point = 23.5° C). The volatility and potency of desflurane prevent its safe use in vaporizers of traditional design. We present a mathematical model which demonstrates the potential for desflurane overdose if contemporary vaporizers are misfilled with desflurane. The most hazardous filling error occurs if an enflurane vaporizer is misfilled with desflurane. The calculated desflurane output of a misfilled enflurane vaporizer at a dial setting of 1% and a temperature of 22° C is 57.8%, or 9.6 MAC. For misfilled enflurane, isoflurane, and halothane vaporizers at dial settings equivalent to one MAC at 22° C, the calculated desflurane output is 14.0, 10.2, and 7.8 MAC, respectively. We conclude that the safe delivery of desflurane will require engineering safeguards, additional monitoring, and education of the anesthesia community.     

Respiratory syncytial virus infection and meningococcal disease.

Although viral respiratory tract infections may predispose to meningococcal disease, strong evidence that they do so exists only for influenza. Data on laboratory reported cases of respiratory syncytial virus (RSV) infections and meningococcal disease in England and Wales from mid-1989 to mid-1994 were analysed. Although the rise in RSV cases preceded the rise in meningococcal disease cases each winter, the interval between the rise and fall of the two diseases was inconsistent, no association was found between time series after removal of the seasonal component, and there was no evidence that more cases of meningococcal disease occurred in winters with more RSV disease. RSV may have less effect on the two most likely mechanisms whereby influenza predisposes to meningococcal disease, namely lowered immunity and impaired pharyngeal defences.     

Anxiety disorders and neuroticism: Are there genetic factors specific to panic?

Data from 2,903 adult same-sex twin pairs were analysed to investigate whether the genetic determinants of symptoms of panic are different from those underlying the neuroticism personality trait. Our results suggest that much of the genetic variation influencing the physical symptoms associated with panic is of the nonadditive type, perhaps due to dominance or epistasis. In both sexes these nonadditive genetic effects on physical symptoms influence the reporting of "feelings of panic". In males they also account for as much as half the genetic variance in neuroticism. The remainder is additive and also accounts for the balance of genetic variation in "feelings of panic". In females genetic variance in neuroticism is entirely additive but is not an important source of covariation with either panic symptom. Thus, symptoms of panic seem to be shaped in part by unique genetic influences which do not affect other anxiety symptoms. That a substantial part of the genetic variance in neuroticism in males may be due to the nonadditive effects on physical symptoms of panic may help to explain the rather low correlation between the genetic influences found to affect neuroticism in males and their counterparts in females.     

Social support,onset of depression and personality

Summary The effects of personality characteristics on social support and hence risk of depression are explored in a group of 150 largely working-class mothers, a subsample of 400 women who took part in a prospective study. This established that once those with depression at first interview were excluded, practically all of the onsets of depression in the follow-up year occurred among 150 women with a severe event or major difficulty — that is a provoking agent. It was also found that low self-esteem and lack of support from a core tie at the time of the crisis was associated with a considerably increased risk. In the subsample as a whole, measures of dependency and attitudinal constraints to support taken at first interview were not associated with risk of depression. But, it is argued, any enduring personality traits that play a role in the link between lack of support and depression would most likely be seen in a smaller group, namely those who had had early inadequate parenting. And the most promising lead concerning the role of personality characteristics did in fact emerge in relation to a small high risk group with such parenting. Most of them had low self-esteem, and they appeared to confide in inappropriate and unreliable sources of support at time of crisis.     

Decontamination and disposal of nitrosoureas and related N-nitroso compounds

An improved procedure for chemically decontaminating residues of nitrosoureas and related N-nitroso compounds ("nitrosamides") commonly used in the cancer research laboratory is proposed. Treatment of accumulated wastes with aluminum:nickel alloy powder while progressively increasing the basicity of the medium consistently led to at least 99.98% destruction of each nitrosamide tested. Hazardous diazoalkanes were never detected in yields of greater than 0.1%. The mutagenicity of the completed reaction mixtures was never more than 3 times background except when the N-nitroso compound contained a 2-chloroethyl group. In most cases, the completeness of reaction could be determined chromatographically, not only to demonstrate the disappearance of the starting N-nitroso compound, but also to follow production of identifiable products in sufficient abundance to account for the starting material destroyed; none of the organic products observed was mutagenic in any of the four tester strains used. The procedure described herein proved reliable in two checker laboratories besides our own when applied to mixtures of seven N-nitroso compounds: N-methyl-N-nitroso-p-toluene-sulfonamide; N-methyl-N-nitrosourethane; N-methyl-N-nitrosourea; N-methyl-N'-nitro-N-nitrosoguanidine; N-ethyl-N-nitrosourea; N-ethyl-N'-nitro-N-nitrosoguanidine; and N-ethyl-N-nitrosourethane. All of the other procedures investigated for destruction of nitrosamides, including the widely used approach of dissolving the nitrosamides in alkali, were associated with important disadvantages.     

The direct access method of teaching reading and the diagnosis and remediation of reading disability

A distinction among reading disabled children based on whether phonetic or semantic deficits predominate has important implications for remediation. Two kinds of reading disability are related to two distinct aspects of the indirect phonological approach used in the vast majority of reading instructions. This approach to determining the meaning is a conversion of the written form of a word to its phonetic counterpart, making the comprehension auditory. Phonetic reading disabled children have a difficulty with the first step in the process, converting the written word to its sound. Semantic reading disabled children can convert the word to its sound, but this does not lead to determining meaning. Significant gains in performance, may occur by using a direct access to meaning, rather than through the intermediary of sound. The Direct Access approach to reading has one premise: Do not use a "word to sound to meaning" approach. The results of a demonstration project indicate the Direct Access approach to reading can be very useful for many reading disabled children.