Nasal transit time in normal subjects and pathologic conditions

A radionuclide method using Tc-99m was used to measure the nasal transit time in 43 patients, including normal smokers and nonsmokers and those with various nasal or paranasal pathologies. The technique described was slightly modified from that already in use in various centers in order to enable more precise measurement. Measurement of transit time of a droplet of Tc-99m phytate on the nasal mucosa appears to differentiate patients with immotile cilia syndrome from normal controls. A positive test, however, can occur also in smokers and in patients with other nasal and paranasal problems. The test is reproducible, cost-effective, and noninvasive, enabling the clinician to make a more appropriate selection of patients needing further investigation.     

Separation of rare cell subpopulations with the aid of biotin-labelled ligands

A universal method for selection of surface marker-positive cells is described. The cells, admixed with an excess of surface marker-negative cells, are In-st labelled with a specific biotinylated ligand and then isolated with the aid of monoclonal, anti-biotin coated beads. The method enables selection and isolation of cells with a frequency as low as 10^-4. The ligand can be an antigen (for selection of infrequent antibody-producing cells), an antibody (for selection of surface antigen-positive cells) or other molecules (for selection of specific receptor-positive cells).     

Assessment of the spatial occurrence of childhood leukaemia mortality using standardized rate ratios with a simple linear Poisson model.

Reports of a suspected cluster of childhood leukaemia cases in West Central Phoenix have led to a number of epidemiological studies in the geographical area. We report here on a death certificate-based mortality study, which indicated an elevated rate ratio of 1.95 during 1966-1986, using the remainder of the Phoenix standard metropolitan statistical area (SMSA) as a comparison region. In the process of analysing the data from this study, a methodology for dealing with denominator variability in a standardized mortality ratio was developed using a simple linear Poisson model. This new approach is seen as being of general use in the analysis of standardized rate ratios (SRR), as well as being particularly appropriate for cluster investigations.     

Mast cell activity in experimental allergic encephalomyelitis

The number and functional reactivity of peritoneal mast cells (MCs) were evaluated in rats with experimental allergic encephalomyelitis (EAE). Cells were counted following staining with toluidine blue and activation was measured by B-hexosaminidase (B-hex) release. The number of detectable MCs and their capacity to release B-hex decreased significantly by 40 and 65%, respectively, as compared with normal controls just prior to the onset of clinical signs. These values returned to normal on clinical recovery. Preliminary data on MC counts performed on histological sections of rat brains with EAE suggested a similar pattern of response, i.e., an early decrease prior to disease onset with subsequent normalization on recovery. In an attempt to modify the course of EAE, rats were treated with the MC stabilizing agent nedocromil or with the MC activating agent, compound 48/80. Nedocromil induced a slight delay in the onset of EAE, but only when administered at the time of EAE induction. Compound 48/80 did not seem to affect the clinical course of the disease. Our results suggest that MCs are involved in the pathogenesis of EAE and may contribute to the induction of the disease rather than to the effector phase and its clinical expression.     

Occupational stress and hypertension

Occupational stress, or job strain, resulting from a lack of balance between job demands and job control, is considered one of the frequent factors in the etiology of hypertension in modern society. Stress, with its multifactorial causes, is complex and difficult to analyze at the physiological and psychosocial levels. The possible relation between job strain and blood pressure levels has been extensively studied, but the literature is replete with conflicting results regarding the relationship between the two. Further analysis of this relationship, including the many facets of job strain, may lead to operative proposals at the individual and public health levels designed to reduce the effects on health and well-being. In this article, we review the literature on the subject, discussing the various methodologies, confounding variables, and suggested approaches for a healthier work environment.     

Trandolapril and endothelin antagonist LU-135252 in the treatment of the fructose-induced hypertensive,hyperinsulinemic, hypertriglyceridemic rat

BACKGROUND: In view of the demonstrated interaction between endothelin and the renin-angiotensin system, the antihypertensive effect of combined therapy with an endothelin antagonist LU-135252 and the angiotensin converting enzyme inhibitor trandolapril, was studied in fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic male Sprague-Dawley rats. METHODS: Forty animals were fed a fructose-enriched diet (Tekled, Harlan) for 5 weeks, as follows: group A, fructose only; group B, trandolapril 0.1 mg/kg/day added during the last 2 weeks; group C, LU-135252 100 mg/kg/day added during the last 2 weeks; group D, both trandolapril and LU-135252 added the last 2 weeks. Systolic blood pressure (BP) was measured weekly in conscious rats by the indirect tail-cuff method. Blood samples from a retro-orbital sinus puncture were taken at the beginning of the experiment and after 3 and 5 weeks and examined for insulin and triglyceride concentrations. RESULTS: Systolic BP decreased in group B (trandolapril) from 148.8 +/- 9.8 at 3 weeks to 138.3 +/- 8.7 mm Hg after 5 weeks; in group C (endothelin antagonist) from 155.1 +/- 5.5 to 142.5 +/- 10.6 mm Hg; and in group D (combination) from 154.6 +/- 10.9 to 121.2 +/- 8.9 mm Hg. Triglyceride levels decreased only in the combined trandolapril/endothelin antagonist group from 167.6 +/- 55.3 in the third week to 134.9 +/- 53.7 mg/dL after 5 weeks. Insulin levels decreased only on combination therapy from 7.4 +/- 3.6 to 5.3 +/- 3.8 ng/mL during the same period. The BP decrease was additive compared with the respective individual substances. CONCLUSIONS: The trandolapril/endothelin antagonist combination appears to offer a rational antihypertensive combination that is superior to that of either drug alone. This finding applies to the specific rat model studied in which BP, insulin, and triglycerides were increased by fructose diet.     

Effects of nifedipine GITS and diuretics in isolated systolic hypertension--a subanalysis of the INSIGHT study

Aims: This study tested the effects on cardiovascular outcomes of treatments based on nifedipine gastrointestinal therapeutic system (GITS) compared with the diuretic combination co-amilozide in a pre-specified subset of patients with isolated systolic hypertension (ISH) enrolled in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study. Major findings: Of 6321 randomized patients, 1498 (23.7%) had ISH with a baseline mean BP of 173/88 mmHg in both treatment groups. Mean BP fell by 29/10 mmHg in the nifedipine and 30/10 mmHg in the diuretic group to a mean BP of 144/78 mmHg and 143/79 mmHg, respectively, at endpoint. The percentage of primary outcomes in patients with ISH was not significantly different between the two treatment groups (nifedipine GITS 6.0%, co-amilozide 6.6%). The number of ISH patients with composite secondary outcomes was 90 (12.2%) in the nifedipine GITS group and 110 (14.5%) in the co-amilozide group (not significant). The incidence rates of primary and secondary outcomes were similar in patients without ISH. Conclusion: In patients with ISH, nifedipine GITS and co-amilozide had similar effects on clinical outcomes and BP lowering. They lend support to international guidelines for the treatment of hypertension recommending the use of long-acting dihydropyridine calcium-channel blockers as one treatment option for patients with ISH.     

Attitudes of Jewish and Bedouin responders toward family physicians’ use of electronic medical records during the medical encounter

Objective

Culture is known to impact expectations from medical treatments. The effects of cultural differences on attitudes toward Electronic Medical Records (EMR) have not been investigated. We compared the attitudes of Jewish and Bedouin responders toward EMR's use by family physicians during the medical encounter, and examined the contribution of background variables to these attitudes.

Methods

86 Jewish and 89 Bedouin visitors of patients in a regional Israeli University Medical Center responded to a self-reporting questionnaire with Hebrew and Arabic versions.

Results

T-tests and a linear regression analysis found that culture did not predict attitudes. Respondents’ self-reported health status, Internet and e-mail use, and estimates of their physician's typing speed explained a total of 18.6% of the variance in attitudes (p < 0.001).

Conclusion

Bedouins respondents’ attitudes toward EMR use were better than expected and similar to those of their Jewish counterparts. The most significant factor influencing respondents’ attitudes was the physician's typing speed.

Practice implications

(1) Further studies should consider the possible impact of cultural differences between the family physician and the healthcare client on attitudes. (2) Interventions to improve physicians’ skill in operating EMRs and typing will potentially have a positive impact on patients’ satisfaction with physicians’ EMR use.     

From the Cover: Father's brain is sensitive to childcare experiences

Although contemporary socio-cultural changes dramatically increased fathers'' involvement in childrearing, little is known about the brain basis of human fatherhood, its comparability with the maternal brain, and its sensitivity to caregiving experiences. We measured parental brain response to infant stimuli using functional MRI, oxytocin, and parenting behavior in three groups of parents (n = 89) raising their firstborn infant: heterosexual primary-caregiving mothers (PC-Mothers), heterosexual secondary-caregiving fathers (SC-Fathers), and primary-caregiving homosexual fathers (PC-Fathers) rearing infants without maternal involvement. Results revealed that parenting implemented a global “parental caregiving” neural network, mainly consistent across parents, which integrated functioning of two systems: the emotional processing network including subcortical and paralimbic structures associated with vigilance, salience, reward, and motivation, and mentalizing network involving frontopolar-medial-prefrontal and temporo-parietal circuits implicated in social understanding and cognitive empathy. These networks work in concert to imbue infant care with emotional salience, attune with the infant state, and plan adequate parenting. PC-Mothers showed greater activation in emotion processing structures, correlated with oxytocin and parent-infant synchrony, whereas SC-Fathers displayed greater activation in cortical circuits, associated with oxytocin and parenting. PC-Fathers exhibited high amygdala activation similar to PC-Mothers, alongside high activation of superior temporal sulcus (STS) comparable to SC-Fathers, and functional connectivity between amygdala and STS. Among all fathers, time spent in direct childcare was linked with the degree of amygdala-STS connectivity. Findings underscore the common neural basis of maternal and paternal care, chart brain–hormone–behavior pathways that support parenthood, and specify mechanisms of brain malleability with caregiving experiences in human fathers.Throughout human history and across cultures, women have typically assumed primary caregiving responsibility for infants (1, 2). Although humans are among the few mammalian species where some male parental caregiving is relatively common, father involvement varies considerably within and across cultures, adapting to ecological conditions (1, 3). Involved fathering has been linked with children''s long-term physiological and social development and with increases in mothers'' caregiving-related hormones such as oxytocin and prolactin (3–6). In addition, animal studies demonstrated structural brain alterations in caregiving fathers (7, 8). It has been suggested that, although maternal caregiving is triggered by neurobiological processes related to pregnancy and labor, the human father''s brain, similar to other biparental mammals, adapts to the parental role through active involvement in childcare (1–3). Despite growing childcare involvement of fathers (3, 5, 6), mechanisms for human fathers'' brain adaptation to caregiving experiences remain largely unknown, and no study to our knowledge has examined the brain basis of human fatherhood when fathers assume primary responsibility for infant care.For social species with lengthy periods of dependence, parental caregiving is key to survival and relies on brain structures that maximize survival (2, 9). Animal studies have demonstrated that mammalian mothering is supported by evolutionarily ancient structures implicated in emotional processing, vigilance, motivation, and reward, which are rich in oxytocin receptors, including the amygdala, hypothalamus, nucleus accumbens, and ventral tegmental area (VTA), and that these regions are sensitive to caregiving behavior (9, 10). Imaging studies of human mothers found activation in similar areas, combined with paralimbic insula-cingulate structures that imbue infants with affective salience, ground experience in the present moment and enable maternal simulation of infant states (11–13). These structures implicate a phylogenetically ancient network of emotional processing that rapidly detects motivationally salient and survival-related cues (14) and enables parents to automatically identify and immediately respond to infant distress, thereby maximizing survival. In humans, this emotional processing network is complemented by a cortical mentalizing network of frontopolar-medial-prefrontal-temporo-parietal structures involved in social understanding, theory of mind, and cognitive empathy, including the medial prefrontal cortex (mPFC), frontopolar cortex, superior temporal sulcus (STS), and temporal poles (15). The mentalizing network plays an important role in individuals'' ability to infer mental states from behavior, is already activated during the parents'' first weeks of parenting, and enables parents to cognitively represent infant states, predict infant needs, and plan future caregiving (11–13).The few studies examining the human father''s brain showed activation in similar areas, including the STS, lateral and medial frontal regions, VTA, inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC) (16, 17). Only one study compared maternal and paternal brain response to infant cues, reporting mothers'' greater amygdala activation, fathers'' greater superior-temporal and medial-frontal activation, and maternal and paternal oxytocin''s different associations with amygdala vs. cortical activation (18). Oxytocin, a nine-amino acid neuropeptide that underpins the formation of affiliative bonds (19), supports the development of human parental caregiving (20). Research has shown that maternal and paternal oxytocin levels are associated with parent–infant synchrony, which is the parent''s careful adaptation of caregiving behavior to infant''s social signals (21). However, although oxytocin levels are similar in mothers and fathers, oxytocin is differentially linked with the parent-specific repertoire, for instance, with affectionate contact in mothers and stimulatory play in fathers (5, 20).Ethological perspectives emphasize the importance of studying the neurobiology of parenting in its natural habitat and of using a behavior-based approach to test parents'' brain adaptation to ecological pressures (22). Consistent with findings in other mammals (10), studies on brain–behavior associations in human mothers describe links between mother–infant synchrony and brain activation in the mother''s subcortical regions, including the amygdala, nucleus accumebens, and hippocampus (11, 13). In contrast, the one study testing human fathers'' brain–behavior associations showed correlations with cortical activation (17). Overall, these findings suggest that distinct brain–hormone–behavior pathways may underpin maternal and paternal care; therefore, oxytocin and parenting behavior may be associated with the emotional processing network in mothers but with the socio-cognitive circuit in fathers. Furthermore, animal studies indicate that active caregiving in biparental fathers leads to greater integration of multiple brain networks involved in nurturance, learning, and motivation (7). Hence, active involvement in caregiving may possibly facilitate integration of both parenting-related networks in human fathers, particularly among those who undertake the primary caregiver role.The present study sought to examine the brain basis of human fatherhood by using a “natural experiment,” afforded for the first time in human history, to our knowledge, by contemporary socio-cultural changes. Throughout history, infants without mothers were cared for by other women (2). Current social changes enable the formation of two-father families raising children with no maternal involvement since birth (3). Such a context provides a unique setting to assess changes in the paternal brain on assuming the traditionally maternal role. Moreover, understanding mechanisms of brain adaptation to caregiving experiences in primary-caregiving fathers may shed further light on processes that refine all fathers'' responses to childcare activities.We visited the homes of two-parent families rearing their firstborn child: heterosexual mother-father couples comprising primary-caregiving mothers (PC-Mothers) and secondary-caregiving fathers (SC-Fathers) and homosexual couples comprising two primary-caregiving fathers (PC-Fathers) (SI Materials and Methods). We videotaped parent–infant interaction in the natural habitat, measured parental oxytocin, and used the videotaped parent–child interactions as stimuli for functional MRI (fMRI) to test parental brain response to infant-related cues. Five hypotheses were proposed. First, we expected activation in both subcortical areas involved in vigilance and reward and cortical circuits implicated in social understanding in all parents raising a young infant. Second, we expected greater subcortical activation in mothers, particularly in the amygdala, which has been repeatedly linked with mammalian mothering (23, 24), and greater activation in cortical socio-cognitive circuits in fathers. Third, the brain–hormone–behavior constellation underpinning maternal care was expected to center around the emotional-processing network, whereas the brain–hormone–behavior links in fathers were expected to coalesce with the socio-cognitive network. Fourth, consistent with the context-specific evolution of human fathering (1), we expected greater variability in fathers'' brain response as mediated by actual caregiving experiences. Such variability would be particularly noted among the primary-caregiving fathers raising infants without mothers and may involve functional integration of the subcortical and cortical networks subserving parenting. Finally, we expected that the pathways leading from the parent''s primary caregiving role to greater parent–infant synchrony would be mediated by parental brain activation and oxytocin levels.