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The Werther effect after television films: new evidence for an old hypothesis.

In this study it was possible to prove the Werther effect in suicides after watching fictional models for the first time. A twice-broadcast (1981, 1982) six-episode weekly serial showing the railway suicide of a 19-year-old male student provided a quasi-experimental ABABA design to investigate differential effects of suicide imitation. Imitation effects were most clearly observable in the groups whose age and sex were closet to those of the model. Over extended periods (up to 70 days after the first episode), the number of railway suicides increased most sharply among 15- to 19-year-old males (up to 175%); the effect steadily decreased in the older age groups, so that no effect was observable for males over 40 years and females over 30 years. Also, the imitation effects remained detectable for longer periods in the groups closest in age to the model. The increases observed after the first and second broadcast for males aged less than 30 years closely corresponded with the respective audience figures for the two showings.

Adolescent

Modelling and suicide: a test of the Werther effect.

The present study investigates whether news about suicides of prominent persons evokes an imitative effect. To this end, daily overall suicide frequencies of a German federal state, Baden-Württemberg, were examined for the years 1968 to 1980 and were related to prominent suicides that were publicized in major newspapers. Data were analysed quasi-experimentally and by means of a time series regression analysis. These methods yielded significant or marginally significant increases, respectively, for the week following the news. Alternative social psychological explanations were examined, and possible statistical artifacts were taken into account. The results are on the whole consistent with the assumption of an imitative effect.

Cross-Sectional Studies

A suicide epidemic in a psychiatric hospital.

The authors report in detail on an epidemic of six inpatient suicides in a psychiatric hospital in Finland. Suggestion and identification had an effect on the timing as well as on the method of four of the suicides. The epidemic is viewed from individual, network, and organizational perspectives. The authors speculate on how such epidemics could be avoided. An increase in inpatient suicide rates has been reported from many countries, and the Werther effect may thus become a topic of considerable importance in psychiatric hospitals in the future.

Adult

[Suicide in pregnancy].

The difficulty in establishing the cause of death of a pregnant woman emphasizes the necessity for the careful gathering of evidence. Especially in the case of motor accidents along lonely stretches of road involving a solitary motorist the possibility of suicide should be taken into consideration. Since a televised suicide had apparently served as model for the method of suicide, mention has been made of the "Werther effect". A literature review reveals that little has been written on the subject-suicide during pregnancy.

Abdominal Injuries

The impact of the live broadcast of Stromae's song L'enfer on social media publications, calls to the national helpline, and suicide attempt rates in France.

On January 9, 2022, Belgian pop singer Stromae performed his new hit "L'enfer" live on French TV. The song addresses his personal struggles with suicidal ideation. To evaluate the impact of Stromae's performance, we modeled the evolution of hospital admission rates for suicide attempts (SAs) in France, calls to the national suicide prevention helpline (3114), and Twitter publications mentioning the singer or the helpline. We employed the Gombay test to identify change points within each time series. We identified a significant increase in mean SA rates among women aged 20-24 years 6 days after the singer's performance. No similar effect was observed in the general population or other young age groups. The show was immediately followed by a peak in tweets referring to the singer, while Twitter activity related to the 3114 remained modest. We did not observe any increase in calls to the helpline. Celebrity testimonies about suicidal experiences can help alleviate stigma but should be accompanied by prevention messages to reduce the risk of contagion.

Humans

Changes in growth hormone concentrations during puberty in adolescents with insulin dependent diabetes.

OBJECTIVE: To document the changes in pulsatile growth hormone secretion in diabetic adolescents during puberty, and to investigate their relationship to both metabolic control and stature. DESIGN: Auxological parameters, overnight growth hormone secretion, fasting IGF-I, hourly glucose and metabolic control were assessed in a group of adolescents with diabetes. PATIENTS: Fifty-two diabetic adolescents (28 males and 24 females) at different pubertal stages and with varying degrees of metabolic control were studied. Ten of those with poor diabetic control were studied on two occasions. MEASUREMENTS: Height and weight measurements, pubertal staging, growth velocity data and bone age estimation were obtained on all the patients. Overnight growth hormone profiles (Pulsar program analysis), glycosylated haemoglobin and fasting IGF-I were performed on all the subjects. Hourly overnight glucose measurements were also obtained on the ten subjects who had two overnight growth hormone studies. RESULTS: For the whole diabetic growth, GH area under curve (AUC) was maximal in late puberty (pubertal stage 4), and was paralleled by maximal GH peak amplitude. No relationship between GH-AUC and metabolic control was demonstrated. No difference in GH parameters was demonstrated between the male and female subgroups. The relationship between growth hormone secretory parameters and stature was not significant. However, GH-AUC was significantly correlated with growth velocity in the males but not the females. CONCLUSIONS: The pattern of GH secretion in adolescents with diabetes parallels that seen in normal adolescents during puberty, with increases in GH concentration associated with increased GH pulse amplitude. The degree of metabolic control had no effect on this pattern and there was no relationship between GH secretory parameters and stature.

Adolescent

Insulin-like growth factors and the developing and mature rat small intestine: receptors and biological actions.

To determine if insulin-like growth factor-I (IGF-I) or multiplication stimulating activity (MSA, rat IGF-II) might directly influence small intestinal epithelium, we studied the distribution of IGF binding sites during development of the rat intestine. Cell membranes from suckling rat mucosa bound 2-6 times as much 125I-IGF-I and 3-5 times as much 125I-MSA as did adult membranes. Isolated villus cells from suckling and adult rats specifically bound both IGFs. IGF-I binding tended to remain high during suckling, whereas MSA binding fell progressively from the early suckling period. Competitive displacement studies with insulin, IGF-I and MSA demonstrated the presence of type-I and type-II IGF receptors. In vitro autoradiography of 125I-IGF-I binding sites in adult and suckling rat jejunum showed highest binding in the submucosa with extensions up into the lamina propria. Immunocytochemical localization of type-II receptors showed highest density in villus epithelium and vessel walls. Administration of MSA by oral and IGF-I by oral and parenteral routes (1 microgram/day for 6 days) to suckling rats stimulated jejunal brush border enzymes, but not intestinal growth. Developmental changes in receptor density and effects on brush border enzymes suggest a specific role for IGFs in post-natal development of the rat intestine.

Animals

Double-blind controlled trial of azathioprine in children with newly diagnosed type I diabetes.

A double-blind controlled trial of azathioprine (2 mg.kg-1.day-1) was conducted with 49 patients aged 2-20 yr (mean 10.8 yr) who had newly diagnosed type I (insulin-dependent) diabetes. Patients were randomly assigned to receive either azathioprine (n = 24) or placebo (n = 25) for 12 mo, beginning within the 20-day period after diagnosis. Baseline clinical and metabolic characteristics did not differ between the two groups. No patient experienced complete remission, defined as restoration of normal carbohydrate tolerance without other treatment. Partial remission, defined as good metabolic control (hemoglobin A1c less than or equal to 7.9%, preprandial blood glucose less than or equal to 8 mM with an insulin dose of less than 0.5 U.kg-1.day-1), occurred in 10 placebo (40%) and 7 azathioprine (29%) patients at 6 mo and in 4 placebo (16%) and 4 azathioprine (17%) patients at 12 mo (differences not significant). Fasting plasma C-peptide was significantly greater in the azathioprine-treated group at 3 and 6 mo, but this difference was not sustained. C-peptide responses to a standard meal and the frequency of islet cell and insulin antibodies did not differ between the two groups over the 12-mo period. Azathioprine caused no significant side effects. We conclude that in the dosage used, and despite early effects on endogenous insulin secretion, azathioprine alone does not influence the remission phase in children with newly diagnosed type I diabetes.

Azathioprine

Mitogenic effects of growth hormone in cultured human fibroblasts. Evidence for action via local insulin-like growth factor I production.

We examined human growth hormone's (hGH) effect on mitogenesis in cultured human fibroblasts, and the role of local insulin-like growth factor I (IGF-I). With 0.5% human hypopituitary serum (HPS), hGH increased thymidine incorporation (TI) over serum-free medium dose responsively, with half-maximal effect at 10 ng/ml (0.5 nM) (hGH 127 +/- 8.8%; IGF-I 107 +/- 1.7% [SEM]) (n = 10). Similarly, with 0.5% HPS, hGH and IGF-I increased cell replication by 172 +/- 8.2% and 169 +/- 25%, respectively (n = 4). Specific IGF-I monoclonal antibody (Sm1.2) dose dependently blunted TI stimulated by 10 ng/ml hGH or IGF-I (at 1:1000, 38 +/- 6.5% and 30 +/- 14% reduction, respectively). Sm1.2 also reduced cell replication by both 10 ng/ml hGH and IGF-I, respectively, to 32% and 42% of stimulated values. Dexamethasone (0.1 microM) synergistically enhanced TI by both IGF-I and hGH. A 28-h time course for TI showed that hGH stimulated a similar peak to IGF-I, lagging in its effect by 4-10 h. We have provided further evidence that hGH stimulates growth of cultured human fibroblasts via local IGF-I production, consistent with IGF-I's paracrine-autocrine role.

Adult

Insulin-like growth factors promote DNA synthesis and support cell viability in fetal hemopoietic tissue by paracrine mechanisms.

There is significant evidence that the insulin-like growth factors (IGF) play a role in both murine and human hemopoiesis. In order to better define the nature and mechanisms of these effects, we have used a serum-free system to examine DNA synthesis and cell replication in murine hemopoietic cells. Cell preparations from 13-day fetal mice livers were incubated in serum-free DMEM alone or with erythropoietin (Epo) 0.5 U/ml, recombinant human IGF-I, purified IGF-II, or recombinant human growth hormone (GH) in various doses, and [3H]thymidine added for the last 3 hr of 21-hr incubation. Cell distribution was over 80% erythroid or erythroblasts. IGF-I and IGF-II promoted thymidine incorporation into cells at a half-maximal dose of 3 and 1 nM respectively, IGF-II with a maximum potency 65% of IGF-I; insulin stimulated at a half-maximum dose of 100 nM, with similar maximum effect to IGF-I, and their effects were not additive. GH was stimulatory at 1 microM. Epo was 2-9 times as effective as IGF-I and their effects were not additive. A monoclonal antibody to IGF-I reduced the effect of IGF-I by 50-80%, had no effect on Epo, and abolished the GH effect. Separation of erythroid cells and precursors from accessory and other liver cells did not alter the response to IGF-I. Cell counts increased in response to IGF-I or Epo, and cell viability was maintained by IGF-I compared to control medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Accelerated endochondral osteoinduction in the absence of bone matrix particles in a rat model system.

Ethanol-precipitated proteins obtained from demineralized rat bone powder (DBP) by 4M guanidine-HCl extraction have been shown to reproducibly induce ectopic endochondral bone formation when subcutaneously implanted in rats in the absence of bone matrix particles. Histologic and biochemical analysis revealed a temporal sequence of chondrocyte differentiation, calcified cartilage formation, neovascularization, osteoblast differentiation, bone formation, osteoclastic bone remodeling, and hematopoietic marrow development that is complete by 21 days. In contrast to previous reports, these results clearly show an osteoinductive response independent of the presence of insoluble extracellular bone matrix. Compared with conventional DBP implants, the guanidine-extractable protein (GE) produces an accelerated and more robust osteoinductive response. Histologically, the initial chondrogenic response at days 6 to 9 is greatly amplified. Alkaline phosphatase specific activity peaks at day 9, several days earlier than for DBP, and is sixfold higher. Calcium accumulation in GE implants at day 12 is fivefold greater than with DBP, and all mineral is localized within the matrix of newly calcified cartilage and new bone. Osteoclasts are up to ninefold more abundant in the rapidly remodeling GE ossicle, making space for hematopoietic marrow. Delivery of GE coprecipitated with inert bone matrix particles was also more effective than DBP, although the response was somewhat attenuated compared with GE alone. Bony filling of 4-mm defects in rat mandibular rami was elicited by 10 mg of GE and followed an endochondral process with increased neovascularization compared with DBP and unimplanted controls. This guanidine-extractable protein fraction should prove useful for inducing quantities of chondrocytes and osteoclasts for in vitro study, and for analysis of osteoinductive requirements.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase

Effect of N-methyl-N'-nitro-N-nitrosoguanidine on the gastric mucosal barrier in rats.

The gastric mucosal barrier to hydrogen ion (H+) after the administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the rat stomach was studied. Increased H+ back-diffusion was observed 3 hr after oral doses of 1 mg of MNNG over a 3-day period. MNNG in concentrations of 250 microgram/ml, 167 microgram/ml, 86 microgram/ml, and 50 microgram/ml in the presence of acid caused increased H+ back-diffusion across the gastric mucosa within 1 hr. Gastric mucosal barrier disruption by MNNG may play a pathogenic role in gastric carcinogenesis.

Animals

Effect of long-term administration of anticonvulsants on copper, zinc, and ceruloplasmin levels.

Anticonvulsant therapy is known to be associated with elevated plasma copper and ceruloplasmin levels. To investigate the effect of long-term phenytoin and/or phenobarbital administration, plasma copper, zinc, and ceruloplasmin levels were measured in two groups of patients with developmental disorders who were either living at home (study 1) or institutionalized (study 2). Plasma copper and zinc levels were measured using an atomic absorption spectrophotometric method, and ceruloplasmin levels were determined using a method measuring oxidase activity (study 1) and an immunodiffusion plate method (study 2). In both studies, the mean plasma copper and ceruloplasmin levels of the anticonvulsant groups were significantly higher than those of control groups, while the mean plasma zinc levels for the anticonvulsant and control groups were similar. Possible change in the tissue zinc/copper ratio among the patients receiving long-term anticonvulsants is discussed.

Adolescent

The regulation of basal pancreatic polypeptide levels in dogs.

In response to various stimuli, pancreatic polypeptide (PP) release is predominantly mediated by cholinergic mechanisms, and may be modulated by sympathetic and opiate (inhibitory) effects. However, the mechanisms regulating basal PP levels remain unclear. We examined the possible role of the sympathetic nervous system and endogenous opiates in the regulation of basal levels of pancreatic polypeptide in trained conscious dogs. During prolonged (150 min) alpha- or beta-adrenergic blockade with phentolamine and propranolol, separately or in combination, there was no change in the basal PP levels of 154 +/- 20 pg/ml. Effective adrenergic modulation of pancreatic hormones was evident since alpha blockade led to a rise in insulin and glucagon, beta blockade led to a fall in insulin and glucagon, while combined alpha- and beta-adrenergic blockade did not affect insulin or glucagon. Opiate blockade with naloxone (1.25 mg followed by 1 microgram/kg/min) led to a delayed fall in PP from 153 +/- 22 to 89 +/- 15 pg/ml at 90 min (no change by 30 min), without a change of insulin or glucagon. Infusion of a potent morphine analogue D-Met2-Pro5-enkephalinamide (0.5 microgram/kg/min) led to a sustained fall in PP to 91 +/- 8 pg/ml by 30 min without a change in insulin or glucagon. Somatostatin infusion (0.2 microgram/kg/min) with insulin and glucagon replacement, led to a similar sustained fall in PP. It is concluded that in dogs: in contrast to insulin and glucagon, at basal conditions the plasma level of PP is not modulated by endogenous alpha- or beta-adrenergic influences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Physiological insulin action is opposed by beta-adrenergic mechanisms in dogs.

To investigate the possible role of adrenergic mechanisms in modulating glucose homeostasis during physiological insulin changes, we studied the effects of alpha-, beta-, or combined alpha- and beta-adrenergic blockade on glucose production (Ra) and utilization (Rd) via isotope ([3-(3)H]glucose) dilution during nonstressful, nonhypoglycemic conditions in response to physiological insulin changes in conscious dogs. Without adrenergic blockade, infusion of insulin at 0.275 mU.kg-1.min-1 (control) caused glucose to fall from 92 +/- 4 to 82 +/- 4 mg/dl over 30 min, because of transient fall in Ra from 2.8 +/- 0.4 to 2.3 +/- 0.3 mg.kg-1.min-1, which recovered to base line by 30 min. There was a later rise in Rd to 3.9 +/- 0.4 mg.kg-1.min-1 at 45 min, but no counter-regulatory hormonal changes (glucagon, cortisol, epinephrine, and norepinephrine) to account for these findings in glucose kinetics. alpha-Blockade alone led to an initial rise in base-line insulin and consequent fall in glucose, associated with a transient fall in Ra but no change in Rd; infusion of insulin led to a further small fall in glucose, with no change in Ra, but with a rise at 30 min in Rd similar to controls. beta-Blockade alone led to an initial fall in insulin and modest rise in glucose; insulin infusion led to a greater rate of fall in glucose than in controls (from 112 +/- 6 to 78 +/- 7 mg/dl over 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists

Oxandrolone increases final height in Turner syndrome.

In order to examine whether the anabolic steroid oxandrolone has any long-term effect on height in Turner syndrome, the short- and long-term effects were studied in a group of 35 individuals with the syndrome. At commencement of treatment, age range was 8.2-16 years (mean 12.9); oxandrolone dosage was 0.07-0.26 mg/kg per day (mean 0.14 mg/kg per day) and continued for 12 months-6 years (mean 33 months), ending at 12-18.5 years (mean 15.6 years). Height velocity increased significantly on therapy from 3.3 +/- 0.1 to 5.8 +/- 0.3 cm/year at 6 and 12 months, and maintained at 4.8 +/- 0.3 cm/year by two years (all P less than 0.001). Girls who were younger and whose bone age was delayed grew faster (P less than 0.001). Oxandrolone dose correlated with height velocity at 12 (r = 0.39, P less than 0.05) and 18 months (r = 0.31, P less than 0.05). Both height standard deviation score (SDS) and estimated mature height (EMH) increased significantly by the end of treatment (-0.31 +/- 0.2 to 0.45 +/- 0.2, and 140.4 +/- 1.1 cm to 144.4 +/- 1.1 cm respectively (both P less than 0.0001). In 23 patients who had completed growth at a mean age of 20.6 +/- 0.83 years, final height was 145.5 +/- 1.3 cm. This was not significantly different from EMH of 144.9 +/- 1.3 cm at the end of therapy, and based on a pre-treatment EMH of 140.5 +/- 1.3 cm, represented a mean height gain of 5 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent