Inherited anxiety-related parent-infant dyads alter LHPA activity.

The pathogenesis of post-traumatic stress disorder (PTSD) is incompletely understood. We hypothesize that disruptions in mother-child relations may be a key contributor to development of PTSD. A normal and healthy separation-individuation process requires adaptations of self- and interactive contingency in both the mother and her child, especially in early childhood development. Anxious mothers are prone to overprotection, which may hinder the individuation process in their children. We examined long-term stress hormones and other stress markers in subjects three generations removed from the Holocaust, to assess the long-term consequences of inherited behavioral and physiological responses to prior stress and trauma. Jewish subjects who recalled overprotective parental behavior had higher hairsteroid-concentrations and dampened limbic-hypothalamic-pituitary-adrenal (LHPA) axis reactivity compared to German and Russian-German subjects with overprotective parents. We suggest that altered LHPA axis activity in maternally overprotected Jewish subjects may indicate a transmitted pathomechanism of "frustrated individuation" resulting from cross-generational anti-Semitic experiences. Thus measurements of hairsteroid-concentrations and parenting practices may have clinical value for diagnosis of PTSD. We propose that this apparent inherited adaptivity of LHPA axis activity could promote higher individual stress resistance, albeit with risk of an allostatic overload.

Persistent LHPA Activation in German Individuals Raised in an Overprotective Parental Behavior.

Parental upbringing may affect their offspring's mental state across the entire lifespan. Overprotective parental child-rearing style may increase the disease burden in the offspring. Furthermore, this child-rearing style may also play a pathogenetic role by transmitting trauma- and stressor-related disorders (TSRD) across generations. Studies with animals have demonstrated that the mother's immediate and expansive protection of the newborn decreases the limbic-hypothalamic-pituitary-adrenal (LHPA) axis activity in the offspring. However, few studies have investigated how stress impact humans raised in an overprotective manner. In a cross-sectional study with 40 healthy students recalling their overprotective upbringing, we show an increase in the dehydroepiandrostendione (DHEA) concentration and a reduction in the cortisol/DHEA-ratio in hair. Additionally, this child rearing style was associated with heightened indications of mental burden, depressiveness, and sense of coherence. Our results provide insight into the roots and consequences of psychological trauma across several generations. Further investigations focusing particularly on multigenerational transmission in extremely burdened families will augment our results.

Circumcision does not alter long-term glucocorticoids accumulation or psychological effects associated with trauma- and stressor-related disorders.

Male infants and boys through early adolescence can undergo circumcision either for the sake of upholding religious traditions or for medical reasons. According to both, Jewish as well as Islamic tenets, circumcision is a religious rite symbolizing the bond with God. The World Health Organization (WHO), the United Nations Council (UNC) as well as the American Academy of Pediatrics (AAP), and the Centers for Disease Control and Prevention (CDC) strongly recommend circumcision to promote hygiene and prevent disease. This procedure has frequently been criticized by various communities claiming that circumcision in infancy and early adolescence were psychologically traumatizing with medical implications up into old age. Due to the lack of evidence concerning an alleged increase in vulnerability, we measured objective and subjective stress and trauma markers, including glucocorticoids from hair samples, in circumcised and non-circumcised males. We found no differences in long-term limbic-hypothalamic-pituitary-adrenal axis activity, subjective stress perception, anxiety, depressiveness, physical complaints, sense of coherence and resilience. Rather, an increase in the glucocorticoid levels indicated a healthy lifestyle and appropriate functioning. Thus, our findings provide evidence that male circumcision does not promote psychological trauma. Moreover, a qualitative approach, the ambivalence construct, was used for the discussion, aiming at a discourse devoid of biases.

Pilot study of adrenal steroid hormones in hair as an indicator of chronic mental and physical stress.

Currently, the quantitative analysis of moderators affecting the function of the hypothalamus-pituitary-adrenal (HPA)-axis in health and sickness is still unreliable. This is, in particular, due to physiological factors such as pulsatile ultradian and circadian glucocorticoid secretion as well as to methodological limitations of the current techniques for steroid hormone determination. Based on this background, the determination of long-term hair steroid concentrations is an important methodological improvement allowing for the quantitative analysis of chronic HPA axis-activation. In order to determine the relationship between chronic mental and physical stress and a chronic activation of the HPA axis, we performed a cross-sectional pilot-study with 40 healthy students and examined the relationships between physical activity, mental burden(s), subjective stress perceptions, depressiveness, anxiety, physical complaints, sense of coherence, resilience, and the long-term integrated steroid hormone levels in hair. The results showed that the concentrations of cortisol, cortisone, and dehydroepiandrosterone in hair were significantly correlated to mental (p = 0.034) and physical stress (p = 0.001) as well as to subjective stress perception (p = 0.006). We conclude that steroid concentrations in hair are decisive predictors for an increase in the long-term-HPA axis activity. Moreover, this biomarker is suitable for capturing the stresslevel after burdening events and physical activity.

The influence of anaesthetics on the increase in the water permeability of the toad bladder induced by vasopressin.

1 Single lobes of the bladder of Bufo marinus were isolated and filled with, and suspended in, oxygenated Ringer solution. The fluid in contact with the outside (serosa) of the lobes had a total osmolarity of 225 m-osmol/litre, and that bathing the inside (mucosa) of 45 m-osmol/litre.2 Osmotic water flow from mucosa to serosa was measured by weighing the lobes every 30 minutes. It was negligible unless vasopressin was added to the serosal bath. Standard concentrations of either 1.25 or 6.25 mu/ml were used to render the bladder lobes permeable to water.3 The presence in the serosal medium of pentobarbitone or thiopentone in concentrations ranging from 0.25 to 2.5 mM, or of chloralose in concentrations ranging from 0.65 to 6.5 mM, diminished the increase in water permeability induced by vasopressin.4 The three anaesthetics exerted similar inhibitory effects on the action of vasopressin from the serosal and from the mucosal surface of the bladder.5 In the presence of a constant high concentration of anaesthetic, increasing the concentration of vasopressin over three orders of magnitude led to stepwise increases of osmotic water flow out of the lobes, although at every dose level the effect of vasopressin was depressed by the anaesthetic. However, it was not completely abolished even if the concentration of vasopressin was close to threshold.6 The increase in water permeability of the bladder induced by 3',5'-adenosine monophosphate (cyclic AMP) was also depressed by the three anaesthetics.7 Possible explanations of the findings are discussed.

[Results from a general training hospital for the implementation of a diagnostic workup for pulmonary embolism according to the Dutch Institute for Health Care Improvement]. / Resultaten van het invoeren van diagnostiek naar longembolie volgens de CBO-richtlijn in een algemeen opleidingsziekenhuis.

OBJECTIVE: To evaluate the active implementation of the Dutch Institute for Healthcare Improvement's guideline for the diagnostic work-up for pulmonary embolism in a general training hospital, and to analyse reasons for not following the guideline strategy. DESIGN: Partly retrospective and partly prospective. METHOD: The diagnostic strategy was analysed for all consecutive patients with clinically suspected pulmonary embolism who underwent a perfusion lung scintigraphy. The extent to which the guideline was followed was investigated in the year before (July 1999-June 2000; n = 384) and the year after (July 2000-June 2001; n = 380) its active implementation. The possible reasons for not completing the strategy in the prospective cohort of the study were also analysed. RESULTS: Following a non-high-probability perfusion-ventilation scan, the guideline was completed in 23/117 (20%) patients prior to the implementation and in 50/109 (46%) patients after the implementation of the guideline. In 27% and 60%, respectively, an additional duplex ultrasound of the legs was made to check for deep vein thrombosis, and in 65% and 70% respectively, pulmonary angiography was performed after a normal ultrasound result. The main reasons for not following the diagnostic work-up included low clinical probability (41%, without a proper alternative diagnosis), an alternative diagnosis (36%; pneumonia, heart failure, malignancy) and a reluctance to perform angiography. The mean age of the patients for whom the guideline was completed was lower (51 years) compared to patients for whom the guideline was not followed (65 years; p < 0.001). The risk of not completing the diagnostic workup in accordance with the guideline was six-fold higher for patients > or = 80 years compared with patients < 40 years of age, whereas an alternative diagnosis was not more prevalent in patients > or = 65 years. CONCLUSION: Although active implementation of the guideline-based diagnostic work-up for pulmonary embolism increased the number of adequate diagnoses, the diagnostic work-up was not completed in half of the patients with inconclusive lung scans. The main reasons for this were the advanced age of the patient, alternative diagnoses, and a reluctance to perform pulmonary angiography.

Increased rate of depression and psychosomatic symptoms in Jewish migrants from the post-Soviet-Union to Germany in the 3rd generation after the Shoa.

The mental health status of persons with Jewish background living in Germany is discussed with special regard to social exclusion like anti-Semitism and overprotective parental rearing behavior, as a transmissional factor of the KZ-Syndrome. These stressors are considered in the context of a higher risk for depression/fear and psychosomatic disorders and also abnormal cortisol levels. The present sample (N=89) is derived from the Jewish population currently living in the German region of Saxony aged between 17-36 years that emigrated from the post-Soviet-Union areas. The mean age was 22.9 years. Two questionnaires to detect psychosomatic symptoms (Giessen complaint list (GBB)-24, hospital anxiety and depression scale) and one questionnaire addressing parental rearing behavior (FEE) were employed. Comparisons were drawn with normative data from the literature about the German residential population. In addition, questions were asked concerning the experience of anti-Semitism in Germany and in the post-Soviet-Union areas. A higher prevalence of depression/fear (10.3% versus 18.2%) and psychosomatic symptoms (M=14.03 versus 17.8; t=2.42; P<0.05) was observed in Jewish migrants to Germany as compared with non-Jewish German residents. Furthermore, anti-Semitic experiences in Germany correlated positively with depression (r=0.293; P<0.01) and fear (r=0.254; P<0.05). The anti-Semitic experiences in the post-Soviet-Union areas also correlated positively with limb pain (r=0.41, P<0.01), fatigue symptoms (r=0.296, P<0.01) and psychocardial symptoms (r=0.219, P<0.05). It was also confirmed that the male respondents recalled a controlling and overprotecting maternal rearing behavior more frequently than the German standard random sample (M=15.39 versus 18.6; t=2.68; P<0.01). The latter also correlated significantly positive with epigastric pain (r=0.349; P<0.01). The present results show that depression, fear and psychosomatic problems are common in Jewish residents with a background of migration from the post-Soviet-Union areas to Germany. Apart from the transgenerational passing of psychological traumata and the Holocaust experiences, other stressors like anti-Semitism, control and overprotection as parental rearing measures appear to be important factors specifically contributing to the pathogenesis of the attributed symptoms.

Adrenalectomy for isolated adrenal metastasis after Gamma Knife Surgery for an intracerebral metastasis of non-small-cell lung carcinoma.

Only a limited group of patients with non-small-cell lung cancer (NSCLC) is eligible for treatment with a curative intent. Adrenalectomy for a solitary adrenal metastasis of NSCLC may be curative when combined with resection of the primary tumor. It is unclear whether resection of an isolated adrenal metastasis is justified in patients with a second metastasis. We report a case of successful adrenalectomy with adjuvant chemotherapy in a patient who was previously treated with a right lower lobe resection and subsequent Gamma Knife treatment of an intracranial metastasis. At 20-month follow-up, patient was in a good clinical condition without signs of recurrent disease. In selected cases, adrenalectomy with adjuvant chemotherapy for an adrenal metastasis of NSCLC may be performed successfully, with good short-term results, even after earlier treatment of a cerebral metastasis.

Factors modifying renal tubular bicarbonate reabsorption in the dog.

1. Acute experiments were carried out on anaesthetized dogs during metabolic alkalosis produced by I.V. administration of NaHCO(3). Partial constriction of one ureter led to a significant rise in the HCO(3) (-) threshold, beyond the simultaneous value for the other kidney. The magnitude of the increase was not correlated with the reduction of glomerular filtration.2. Stop-flow analysis, following complete unilateral obstruction of urine flow, demonstrated proximal as well as distal tubular reabsorption of bicarbonate. At any given plasma P(co2) the detailed configuration of the concentration changes which developed depended on (a) the presence and concentration of mannitol, (b) the duration of urinary stasis, and (c) the plasma concentration of HCO(3) (-).3. If a solution containing 15% (w/v) mannitol was infused I.V., the HCO(3) (-) concentration in free flow urine was lower than in plasma, and it fell further during arrest of flow in the entire column of trapped fluid. If less mannitol was infused, or none at all, interruption of urine flow led to a striking increase of HCO(3) (-) concentration in the distal portion of the occluded column, and to a fall in the fluid arrested in the proximal segments.4. It was demonstrated that the HCO(3) (-) concentration attained after 2(1/2), 6, or 15 min of urinary stasis at any point in the trapped fluid column was due to the combined effects of water reabsorption and HCO(3) (-) reabsorption which proceeded independently, and with a different time course.5. If mannitol was administered the lowest urinary HCO(3) (-) concentration in the series moved progressively to a more distal location with increasing duration of urinary stasis. When HCO(3) (-) concentration peaks were present in distal fluid they were conspicuous only after short interruptions of urine flow; during extended stop-flow periods they became attenuated, or disappeared. If no mannitol was administered this did not occur.6. Provided the plasma level of HCO(3) (-) was sufficiently elevated, mannitol (15%, w/v) was administered, and the time available for reabsorption was lengthened by ureter obstruction, much larger concentration differences between plasma and trapped fluid developed than the largest that are ever found between the plasma and freely draining urine. The magnitude of the largest plasma-urine (P-U) concentration difference for HCO(3) (-) increased with intratubular ;contact time', and no limiting value was found.7. Potassium concentration in distal occluded fluid fell with prolonged duration of stasis. This was related to the slow and progressive diminution of distal HCO(3) (-) concentration. But if instead of bicarbonate a nonreabsorbable anion, such as phosphate, was the dominant distal anion, K(+) concentration in distal fractions remained high and rose further with time.