The need for a standard national immunization record

Perhaps the most significant link in achieving the nation's immunization objectives is the extent of parental knowledge. Admittedly, this is a weak link. The 1990 federal objectives calling for an official format using common guidelines for completion of immunizations, though well-conceived, has not been used exclusively by health care givers. The lack of accord has permitted the proliferation of many different immunization records that are not only confusing to parents, but also to health care providers at times. A standard national immunization record could be an essential element in strengthening the weak link of parental knowledge of immunizations and stressing the importance of preserving such a record for a lifetime.     

Intrinsic positive end-expiratory pressure in Acute Respiratory Distress Syndrome (ARDS) Network subjects

OBJECTIVE: We tested the hypothesis that subjects randomized to the 6 mL/kg predicted body weight tidal volume study group of the National Institutes of Health Acute Respiratory Distress Syndrome (ARDS) Network study had higher levels of intrinsic positive end-expiratory pressure (PEEP) than subjects randomized to the 12 mL/kg predicted body weight tidal volume study group. DESIGN: Secondary analysis of a subgroup from a randomized controlled trial. SETTING: Hospitals located in San Francisco, CA, and Seattle, WA. PATIENTS: Eighty-four patients enrolled in the ARDS Network tidal volume trial in San Francisco, CA, and Seattle, WA, with records of measurement of intrinsic PEEP. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intrinsic PEEP was assessed a median of six times over the first 48 hrs of ARDS Network protocol ventilation in study subjects, with no significant difference in number of measurements between subjects randomized to the tidal volume protocol of 6 mL/kg compared with 12 mL/kg. We found that intrinsic PEEP was higher among subjects randomized to the 6 mL/kg protocol, with a median intrinsic PEEP of 1.3 cm H2O (interquartile range, 0-3.1 cm H2O), compared with a median intrinsic PEEP of 0.5 cm H2O (interquartile range, 0-1.5 cm H2O) among subjects randomized to 12 mL/kg (p = .029). There was no difference in total PEEP between the study groups. CONCLUSIONS: In a subgroup of ARDS Network subjects, intrinsic PEEP was statistically significantly higher in subjects randomized to the 6 mL/kg protocol than those in the 12 mL/kg study group. The amount of intrinsic PEEP was very low in both study groups, and difference of median intrinsic PEEP between the groups was <1 cm H2O. It is unlikely that the difference in intrinsic PEEP between the study groups was clinically important in the ARDS Network study of low tidal volume ventilation.     

Antinociceptive, brain-penetrating derivatives related to improgan, a non-opioid analgesic

The antinociceptive profile of selected histamine H(2) and histamine H(3) receptor antagonists led to the discovery of improgan, a non-brain-penetrating analgesic agent which does not act on known histamine receptors. Because no chemical congener of improgan has yet been discovered which has both antinociceptive and brain-penetrating properties, the present study investigated the antinociceptive effects of a series of chemical compounds related to zolantidine, a brain-penetrating histamine H(2) receptor antagonist. The drugs studied presently contain the piperidinomethylphenoxy (PMPO) moiety, hypothesized to introduce brain-penetrating characteristics. Following intracerebroventricular (i.c.v.) dosing in rats, six of eight drugs produced dose- and time-related antinociception on both the tail flick and hot plate tests over a nearly eight-fold range of potencies. Ataxia and other motor side effects were observed after high doses of these drugs, but two of the compounds (SKF94674 and loxtidine) produced maximal antinociception at doses which were completely devoid of these motor effects. Consistent with the hypothesis that PMPO-containing drugs are brain-penetrating analgesics, SKF94674 and another derivative (JB-9322) showed dose-dependent antinociceptive activity 15 to 30 min after systemic dosing in mice, but these effects were accompanied by seizures and death beginning 45 min after dosing. Other drugs showed a similar pattern of antinociceptive and toxic effects. In addition, loxtidine produced seizures without antinociception, whereas zolantidine produced neither effect after systemic dosing in mice. Although several of the drugs tested have histamine H(2) receptor antagonist activity, neither the antinociception nor the toxicity was correlated with histamine H(2) receptor activity. The present results are the first to demonstrate the existence of brain-penetrating antinociceptive agents chemically related to zolantidine and improgan, but further studies are needed to understand the mechanisms of both the pain relief and toxicity produced by these agents.     

A model of mother–child adjustment in Arab Muslim immigrants to the US

We examined the mother–child adjustment and child behavior problems in Arab Muslim immigrant families residing in the U.S.A. The sample of 635 mother–child dyads was comprised of mothers who emigrated from 1989 or later and had at least one early adolescent child between the ages of 11 and 15 years old who was also willing to participate. Arabic speaking research assistants collected the data from the mothers and children using established measures of maternal and child stressors, coping, and social support; maternal distress; parent–child relationship; and child behavior problems. A structural equation model (SEM) was specified a priori with 17 predicted pathways. With a few exceptions, the final SEM model was highly consistent with the proposed model and had a good fit to the data. The model accounted for 67% of the variance in child behavior problems. Child stressors, mother–child relationship, and maternal stressors were the causal variables that contributed the most to child behavior problems. The model also accounted for 27% of the variance in mother–child relationship. Child active coping, child gender, mother's education, and maternal distress were all predictive of the mother–child relationship. Mother–child relationship also mediated the effects of maternal distress and child active coping on child behavior problems. These findings indicate that immigrant mothers contribute greatly to adolescent adjustment, both as a source of risk and protection. These findings also suggest that intervening with immigrant mothers to reduce their stress and strengthening the parent–child relationship are two important areas for promoting adolescent adjustment.     

Actions of tacrine and galanthamine on histamine-N-methyltransferase

Histamine-synthesizing neurons in the brain may play an important role in cognition, and a histaminergic deficit has been found in Alzheimer's disease (AD). The AD medication tacrine was previously shown to inhibit some forms of rodent histamine-N-methyltransferase (HNMT), but the effects of AD drugs have not been investigated on human HNMT activity. Presently, the effects of tacrine and galanthamine (another AD medication) were studied on the activity of several forms of human and rat HNMT. Tacrine (0.01-10 microM) inhibited both human and rat HNMT activity in a concentration-dependent manner, but was less potent on both human embryonic kidney and recombinant human brain HNMT than on rat kidney HNMT (IC50 values were 0.46 and 0.70 microM vs. 0.29 microM, respectively). Galanthamine (up to 10 microM) did not influence the activity of rat kidney or human HNMT. Tacrine, but not galanthamine, may achieve brain levels sufficient to influence histamine metabolism in some patients treated for AD.     

4α-phorbol 12,13-didecanoate activates cultured mouse dorsal root ganglia neurons independently of TRPV4

Background and Purpose

The Ca²⁺-permeable cation channel TRPV4 is activated by mechanical disturbance of the cell membrane and is implicated in mechanical hyperalgesia. Nerve growth factor (NGF) is increased during inflammation and causes mechanical hyperalgesia. 4α-phorbol 12,13-didecanoate (4αPDD) has been described as a selective TRPV4 agonist. We investigated NGF-induced hyperalgesia in TRPV4 wild-type (+/+) and knockout (–/–) mice, and the increases in [Ca²⁺]_i produced by 4αPDD in cultured mouse dorsal root ganglia neurons following exposure to NGF.

Experimental Approach

Withdrawal thresholds to heat, von Frey hairs and pressure were measured in mice before and after systemic administration of NGF. Changes in intracellular Ca²⁺ concentration were measured by ratiometric imaging with Fura-2 in cultured DRG and trigeminal ganglia (TG) neurons during perfusion of TRPV4 agonists.

Key Results

Administration of NGF caused a significant sensitization to heat and von Frey stimuli in TRPV4 +/+ and –/– mice, but only TRPV4 +/+ mice showed sensitization to noxious pressure. 4αPDD stimulated a dose-dependent increase in [Ca²⁺]_i in neurons from +/+ and –/– mice, with the proportion of responding neurons and magnitude of increase unaffected by the genotype. In contrast, the selective TRPV4 agonist GSK1016790A failed to stimulate an increase in intracellular Ca²⁺ in cultured neurons. Responses to 4αPDD were unaffected by pretreatment with NGF.

Conclusions and Implications

TRPV4 contributes to mechanosensation in vivo, but there is little evidence for functional TRPV4 in cultured DRG and TG neurons. We conclude that 4αPDD activates these neurons independently of TRPV4, so it is not appropriate to refer to 4αPDD as a selective TRPV4 agonist.     

Plasma renin activity-guided strategy for the management of hypertension

Despite the wide array of antihypertensive agents and the availability of national guidelines regarding treatment for hypertension, the disease remains uncontrolled in nearly 50% of affected patients. Furthermore, the number of patients with resistant hypertension continues to increase. For patients with resistant hypertension, the American Heart Association has advocated for clinical studies to determine appropriate pharmacologic treatment strategies. One proposed strategy involves ambulatory measurement of plasma renin activity (PRA) to guide the selection of antihypertensive therapy. Patients with low PRA would be prescribed natriuretic volume-mediated therapies (e.g., diuretics and calcium channel blockers), whereas those with high PRA would receive antirenin system therapies (e.g., β-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers). This review focuses on the principles of PRA-guided therapy, its historical development, alternative approaches to classifying patients into categories of response to antihypertensive agents, and recent data supporting the use of plasma renin activity-guided hypertension management.     

Sexuality Training,Education and Therapy in the Healthcare Environment: Taboo,Avoidance, Discomfort or Ignorance?

Multiple sources of resistance are present in the healthcare environment to comprehensive assessment and intervention efforts in regard to sexuality. The authors survey both the diversity of needs and values presented by consumers, and encourage providers to equip themselves educationally, emotionally and ethically so that they can deliver relevant, holistic services to consumers.     

Response rates for providing a blood specimen for HIV testing in a population-based survey of young adults in Zimbabwe

Background  

To determine differences among persons who provided blood specimens for HIV testing compared with those who did not among those interviewed for the population-based Zimbabwe Young Adult Survey (YAS).