Cerebrospinal fluid (CSF) shunting and ventriculocisternostomy (ETV) in 400 pediatric patients. Shifts in understanding, diagnostics, case-mix, and surgical management during half a century.

OBJECTIVE: To characterize shifts from the 1960s to the first decade in the 21st century as to diagnostics, case-mix, and surgical management of pediatric patients undergoing permanent CSF diversion procedures. METHODS: One hundred and thirty-four patients below 15 years of age were the first time treated with CSF shunt or ETV for hydrocephalus or idiopathic intracranial hypertension (IIH) in 2009-2013. This represents our current practice. Our previously reported cohorts of shunted children 1967-1970 (n = 128) and 1985-1988 (n = 138) served as backgrounds for comparison. RESULTS: In the 1960s, ventriculography and head circumference measurements were the main diagnostic tools; ventriculoatrial shunt was the preferred procedure (94 %), neural tube defect (NTD) was the leading etiology (33 %), and overall 2-year survival rate was 76 % (non-tumor survival 84 %). In the 1980s, computerized tomography (CT) was the preferred diagnostic imaging tool; ventriculoperitoneal shunt (VPS) had become standard (91 %), the proportion of NTD children declined to 17 %, and the 2-year survival rate was 91 % (non-tumor survival 95 %). Hydrocephalus caused by intracranial hemorrhage had, on the other hand, increased from 7 to 19 %. In the years 2009-2013, when MRI and endoscopic third ventriculocisternostomy (ETV) were matured technologies, 73 % underwent VPS, and 23 % ETV as their initial surgical procedure. The most prevalent etiology was CNS tumor (31 %). The proportion of NTD patients was yet again halved to 8 %, while intracranial hemorrhage was also reduced to 12 %. In this last period, six children were treated with VPS for Idiopathic Intracranial Hypertension (IIH) due to unsatisfactory response to medical treatment. They all had headache, papilledema, and visual disturbances and responded favorably to treatment. The 2 years of survival was 92 % (non-tumor survival 99 %). In contrast to the previous periods, there was no early shunt related mortality (2 years). Aqueductal stenosis was a small but distinctive group in all cohorts with 5, 6 and 3 % respectively. CONCLUSIONS: The case-mix in pediatric patients treated with permanent CSF diversion has changed over the last half-century. With the higher proportion of children with CNS tumor patients and inclusion of the IIH children, the median age at initial surgery has shifted substantially from 3.2 to 14 months. Between the 1960s and the current cohort, 2 years of all-cause mortality fell from 24 to 8 %. Prolonged asymptomatic periods, extending 15 years, were relatively common. Nevertheless, 18 patients experienced shunt failure more than 15 years after last revision, and first-time shunt failure has been observed 29 years after initial treatment. This underscores the importance of life-long follow-up.

Intracellular Localization of Phospholipase D in Leaves and Seedling Tissues of Castor Bean.

The intracellular distribution of phospholipase D (PLD; EC 3.1.4.4) in castor bean (Ricinus communis L.) tissues was investigated by subcellular fractionation and by immuno-electron microscopy. Centrifugal fractionation revealed that most PLD in young leaves was soluble, whereas in mature leaves a majority of PLD was associated with microsomal membranes. Further separation of microsomal membranes by a two-phase partitioning system indicated that PLD was associated with both plasma and intracellular membranes. Sucrose gradient separation of intracellular membranes showed PLD present in the endoplasmic reticulum, a submicrosomal band, and in soluble fractions but not in mitochondria and glyoxysomes of postgermination endosperm. Immunocytochemical studies found high gold labeling in vacuoles in young leaves, suggesting that the high level of soluble PLD in young leaves is due to release of PLD from vacuoles during tissue disruption. In addition to the labeling in vacuoles, gold particles were also found in the cytoplasmic matrices and plasma membrane in leaves and in 2-d postgermination seedlings. Collectively, these results show that PLD in castor bean leaf and seedling tissues is localized in the vacuole and is associated with the endoplasmic reticulum and plasma membrane and that the relative distribution between the soluble and membrane compartments changes during castor bean leaf development.

Reliability of the telephone interview in diagnosing anxiety disorders.

The reliability of psychiatric diagnosis using the Schedule of Affective Disorders and Schizophrenia-Lifetime Version in personal and telephone interviews with 39 subjects was assessed using a 12- to 19-month test-retest design. Interrater reliability was high (kappa, .69 to .84) for the diagnosis of panic disorder, agoraphobia with panic attacks, probable panic disorder, major depression, and alcohol abuse. We conclude that it is possible to reliably make these lifetime diagnoses in a family study using the telephone interview.

Basal lamina anionic sites in the embryonic submandibular salivary gland: resolution and distribution using ruthenium red and polyethyleneimine as cationic probes.

The basal lamina of the embryonic submandibular epithelium is a dynamic compartment of the extracellular matrix required for branching morphogenesis. A transmission electron microscopy (TEM) structural analysis of the basal lamina, at a time of intense branching activity, was conducted, comparing standard glutaraldehyde-fixed preparations with ones that included tannic acid in the primary fixative, and comparing anionic site resolution and distribution with two cationic probes, ruthenium red (RR) and polyethyleneimine (PEI). Standard TEM revealed a conventional basal lamina structure, with a lamina densa, a lamina lucida interna and a lamina lucida externa. Fine filaments emanated from the lamina densa, traversing both lamina lucidae. Tannic acid revealed approximately 35 nm diameter electron-dense particles in the lamina densa with a spacing repeat of approximately 45 nm. Basal lamina anionic sites were resolved as approximately 26 nm diameter RR-particles and approximately 50 nm diameter PEI-particles, present in the lamina lucida interna and associated with the lamina lucida externa. RR-particle linear spacing was 70 nm in the externa and 50 nm in the interna, while the PEI-particle spacing repeat was 90 nm in both compartments. Binding of both probes was blocked by testicular hyaluronidase or chondroitinase treatment, a result suggesting that the anionic sites were chondroitin sulfate proteoglycan, hyaluronic acid, or both. The greater particle spacing observed with PEI was not simply a physical limitation resulting from the average PEI particle diameter being almost twice that of RR particles, since PEI-resolved anionic sites on interstitial collagen were much more closely spaced (approximately 60 nm) than RR-resolved sites (approximately 105 nm).(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroid adenoma in a subject with familial hypocalciuric hypercalcemia: coincidence or causality?

A middle-aged woman presented with a history of constipation, easy fatigue, depressive mood, lassitude, polydipsia, and polyuria. The patient posed a challenging diagnostic dilemma due to the presence of persistent severe hypercalcemia and relative lack of clinically manifested symptoms. Clinical, biochemical, and genetic examinations confirmed the diagnosis of familial hypocalciuric hypercalcemia as a result of C562Y calcium-sensing receptor mutation, and a coexisting parathyroid adenoma. After adenectomy, the patient's clinical situation improved markedly, and a modest equilibrium hypercalcemia persisted. This case presents an unusual combination of two relatively common endocrine disorders.

Magnetic resonance imaging evaluation of adipose tissue and muscle tissue mass in children with growth hormone (GH) deficiency, Turner's syndrome, and intrauterine growth retardation during the first year of treatment with GH.

Measurement of muscle and fat tissue mass by magnetic resonance imaging of the thighs was used to study the metabolic effect of human (h) GH in 23 GH deficiency, 8 Turner's syndrome, and 14 intrauterine growth retardation prepubertal patients. They were evaluated before and 1, 3, 6, and 12 months after the onset of hGH treatment. Seven normal children were followed longitudinally as controls. During hGH treatment, a significant increase in muscle tissue and decrease in adipose tissue cross-sectional areas was observed, leading to a dramatic increase in the muscle/adipose tissue cross-sectional area ratio in each period studied. These findings remained highly significant when corrected for the small variation observed in controls. The body mass index was correlated with muscle and adipose tissue cross-sectional area at each time point (P < 0.0001). The muscle cross-sectional area increment correlated with the first year height velocity (P < 0.01). This study indicates that in children with and without GH deficiency, hGH therapy induces rapid and intense variation of muscle and adipose tissue mass, and that magnetic resonance imaging can be used to study some aspects of the metabolic actions of GH.

Human growth hormone treatment of short-stature children born small for gestational age: effect on muscle and adipose tissue mass during a 3-year treatment period and after 1 year's withdrawal.

In addition to its growth promoting effect, GH has profound metabolic effects that have not always been evaluated in longitudinal studies. We have recently shown that the effect of GH on body composition can be evaluated by magnetic resonance imaging measurement of adipose and muscle tissue cross-sectional (cs) areas in the thigh. The aim of this study was to evaluate the long-term effects of human GH (hGH) (0.2 IU/kg day) on muscle and adipose tissue mass during a 3-yr treatment period and after 1 year's withdrawal in short SGA (small for gestational age) children. Measurement of muscle and fat tissue mass by magnetic resonance imaging of the thighs was used to study the metabolic effect of hGH in 14 prepubertal short children born SGA. Results were compared with those of a control group of 7 normal children followed longitudinally. An increase of muscle tissue cs area was observed during the 3 yr of hGH treatment, an increase which was significantly different during the first 2 yr of treatment from that seen in controls (+31.2+/-2.6% and +18.1+/-1.8% during the 1st and 2nd year, respectively, vs. +9.1+/-2.6% change during 1 yr in controls). After a significant decrease in adipose tissue cs area during the first year of therapy (-16.4+/-3.4% vs. baseline values), an increase in adipose tissue cs area occurred during the second and third years. At the end of the third year, the muscle tissue cs area change was significantly greater in SGA-treated children, as compared with controls (+71.6+/-4.6% vs. 22.1+/-4.6%; P < 0.001), whereas the adipose tissue cs area change was similar in the two groups (+12.6+/-9.5% vs. +19.9+/-4.2%). After hGH withdrawal, the effects were opposite after 3 months, as compared with those observed after the first 3 months of hGH administration, whereas no additional significant change was seen after 1 yr off treatment, indicating the maintenance of muscle and adipose tissue mass. In conclusion, hGH administered to SGA children is effective in improving growth velocity and has long-term effects on muscle and adipose tissue mass. These effects may lead to speculation about the sensitivity of these tissues to GH. The physiological consequences of such effects must be evaluated.

Effect of hypertonic saline infusion on the level of immunoreactive dynorphin in extracted human plasma.

Dynorphin-A and its related peptides are derived from prodynorphin, one of the three known endogenous opioid precursors. The prodynorphin gene is expressed in the vasopressinergic magnocellular neurons of the hypothalamus, while its peptide products are present in the vasopressin (AVP) neurosecretory vesicles of the neurohypophysis. The concentration of immunoreactive (IR) dynorphin is orders of magnitude higher in the neurohypophysis than in any other tissue, suggesting that perhaps the prodynorphin-derived peptides are secreted from the hypothalamic-neurohypophyseal unit into the general circulation. Experiments in rats have shown that osmotic stimuli increase both AVP and prodynorphin in the hypothalamus. To determine whether human hypothalamic prodynorphin is also under osmotic regulation, we measured plasma IR-dynorphin, plasma IR-AVP, and serum sodium immediately before and during the infusion of normal or hypertonic saline in normal human volunteers. Because of the unusual susceptibility of the prodynorphin-derived peptides to cleavage by endopeptidases, we also developed an appropriate plasma dynorphin extraction technique. We found that the IR-dynorphin present in human plasma was composed of 6K- and 4K-sized peptides and that no larger than 6K or smaller than 4K dynorphins were present. The infusion of normal saline did not have any significant effect on plasma IR-dynorphin, while 3% hypertonic saline increased its plasma levels. Thus, the mean IR-dynorphin level in the plasma of the volunteers infused with normal saline was 40.3 +/- 6.4 fmol/mL (mean +/- SE; n = 6) at zero time; after 30 min of infusion, plasma IR-dynorphin was 36.0 +/- 6.3, after 60 min it was 29.9 +/- 5, after 90 min it was 36.0 +/- 4.7, after 120 min it was 36.8 +/- 3.2, and after 150 min it was 36.0 +/- 6.1. The plasma IR-dynorphin level in the volunteers infused with hypertonic saline was 31.7 +/- 3.5 fmol/mL (mean +/- SE; n = 10) at zero time. After 30 min of infusion it increased to 37.4 +/- 3.8, after 60 min to 46.4 +/- 7.7, after 90 min to 56.2 +/- 9.1, after 120 min to 53.6 +/- 8.7, and after 150 min to 99.0 +/- 14.2. The increase in plasma IR-dynorphin with time was significant (P less than 0.0001) and correlated positively with serum sodium and plasma AVP. The physiological role of the prodynorphin-derived peptides of the hypothalamic-neurohypophyseal unit is not yet known.(ABSTRACT TRUNCATED AT 400 WORDS)

Intraoperative evaluation of EuroCollins and University of Wisconsin preservation solutions in patients undergoing hepatic transplantation.

The effects of cold liver preservation with two solutions, EuroCollins and University of Wisconsin, were compared in terms of hepatic function and hemodynamic parameters obtained intraoperatively during orthotopic liver transplantation. Data from 101 consecutive liver transplants were analyzed retrospectively, comparing 50 grafts preserved with EC with 51 preserved with UW solution. Hepatic hemodynamics parameters included portal venous and hepatic arterial flows, determined with an electromagnetic flowmeter. Vascular pressures, blood gases and pH measurements were obtained directly from the portal vein, hepatic vein, and peripheral artery. Serial measurements of serum glucose, SGOT, and SGPT were performed following reperfusion. Preservation related graft failure occurred in 4 of 50 patients in the EC group, but not in any of 51 patients in the UW group. Cold Ischemia time (hours +/- SEM) was significantly prolonged in UW group (7.23 +/- 1.4 vs. 5.21 +/- 0.9). Rate of temperature change (degrees C/hour +/- SEM) after reperfusion was similar in both groups (EC = 0.62 +/- 0.35, UW = 0.71 +/- 0.4). Peak serum SGOT, SGPT, and glucose levels following reperfusion were significantly higher in the EC group, as was PRBC and FFP administration. Systemic hemodynamics in both groups of patients were similar. However, UW-preserved grafts demonstrated a significantly higher hepatic artery resistance, with no other differences in hepatic hemodynamics seen. UW solution appears to extend cold ischemia time without adversely affecting liver function. However, the etiology and clinical significance of the increased hepatic artery resistance seen in UW-stored liver grafts are unknown.

Perioperative renal function in patients undergoing orthotopic liver transplantation. A randomized trial of the effects of verapamil.

Patients who undergo orthotopic liver transplantation often experience a significant drop in GFR postoperatively. Postulated mechanisms include intraoperative hemodynamic changes, suboptimal renal perfusion during the anhepatic stage, and cyclosporine administration. We undertook a prospective double-blind study to investigate these factors, as well as to determine the protective effects of verapamil on perioperative renal function. Twenty-five patients with normal renal function undergoing OLT received either placebo (n = 13) or verapamil (n = 12) intraoperatively and for six weeks post-OLT. No CsA was administered until after reperfusion of the graft liver, and venovenous bypass (VVB) was utilized in all cases. Patients completing six weeks of the study experienced 61% and 48% decreases in GFR within the placebo and verapamil groups respectively. A significant decrease in GFR occurred in the placebo group between one and six weeks post-OLT, and a significant drop in GFR occurred in the verapamil group by one week post-OLT. Differences between the groups were not significant, however. Systemic, renal, and hepatic hemodynamics were similar at all times between groups, and renal hemodynamics and urine output were unchanged during VVB. We conclude that (1) perioperative factors do not contribute to renal dysfunction post-OLT when VVB is used; (2) VVB preserves renal hemodynamics during the anhepatic phase; (3) CsA is the most likely causative agent for post-OLT renal dysfunction; and (4) intraoperative verapamil serves no protective role, as administered in this study.

Murine polyomavirus infection of 3T6 mouse cells shows evidence of predominant necrosis as well as limited apoptosis.

The current study was developed to determine if polyomavirus infected 3T6 mouse cells evoked an apoptotic or a necrotic mechanism during infection. Infected cells were analyzed by flow cytometry, transmission electron microscopy (TEM), DNA electrophoresis and by measuring caspase-3 enzymatic activity. Infected cells that were analyzed at 72 h post-infection showed the following: flow cytometry analysis revealed a 5% increase in apoptotic cells and a 46% increase in necrotic cells when compared to uninfected cells; electron microscopy showed 10% cells with characteristic apoptotic morphology and 40% with necrotic appearance; caspase-3 activity was found to increase two fold when compared to uninfected cells and DNA fragmentation (laddering) was clearly evident late in infection. It was concluded that infected cells predominantly showed necrosis, although some cells showed apoptosis in late infection. Recombinant capsid-like particles composed of the polyomavirus structural proteins were not able to induce cell death.

Danger of amiodarone therapy and elevated inspired oxygen concentrations in mice.

Our study showed a statistically significant incidence of pulmonary edema in mice receiving amiodarone and 100% oxygen. This finding, together with a variety of clinical reports, indicates that in patients receiving amiodarone therapy, FiO2 should be maintained at the lowest possible level, consistent with adequate oxygenation.

Negative correlation between plasma GHRH values and growth velocity in short prepubertal children.

Numerous data suggest that impaired growth hormone secretion in short children is usually related to abnormal regulation of the hormone at the hypothalamic level. In order to improve our understanding of neurohypothalamic dysfunction in short children, we measured basal and peak (after L-dopa stimulation) plasma growth hormone-releasing hormone levels in 43 prepubertal children. Among them, in 23 children suspected of having hypothalamic growth hormone dysregulation, growth hormone-releasing hormone values were significantly higher than those observed in normal short stature children (n = 20), no longer correlated with peak growth hormone following L-dopa, and negatively correlated with growth velocity. This suggests that a predominant inhibitor of growth hormone secretion, such as an increase in somatostatin tone, might be prevalent in a large number of children with partial growth hormone deficiency and suspected hypothalamic growth hormone dysregulation.

Embryonic quail eye development in microgravity.

The US-Russian joint quail embryo project was designed to study the effects of microgravity on development of Japanese quail embryos incubated aboard Mir. For this part of the project, eyes from embryonic days 14 and 16 (E14 and E16) flight embryos were compared with eyes from several groups of ground-based control embryos. Measurements were recorded for eye weights; eye, corneal, and scleral ring diameters; and numbers of bones in scleral ossicle rings. Transparency of E16 corneas was documented, and immunohistochemical staining was performed to observe corneal innervation. In addition, corneal ultrastructure was observed at the electron microscopic level. Except for corneal diameter of E16 flight embryos, compared with that of one of the sets of controls, results reported here indicate that eye development occurred normally in microgravity. Fixation by cracking the shell and placing the egg in paraformaldehyde solution did not adequately preserve corneal nerves or cellular ultrastructure.

Metabolism of vasopressin, oxytocin, and their analogues in the human gastrointestinal tract.

The bioavailability from the gastrointestinal tract of peptides as large as nonapeptides is very low, which may be attributed to extensive lumenal and mucosal degradation. The aim of the present study was to investigate the stability of the neurohypophyseal hormones arginine-vasopressin (AVP), oxytocin (OT), and their synthetic analogues in human intestinal contents, small intestinal brush-border membranes, and gastric, rectal, and colonic plasma membranes. Peptides were incubated in gastrointestinal contents from healthy volunteers and in human intestinal mucosa homogenates. The extent of degradation was determined by reversed-phase high performance liquid chromatography (HPLC). AVP was rapidly degraded in the ileum fractions of the intestinal contents whereas 50% of the analogue 1-deamino-8-D-arginine vasopressin (dDAVP) remained intact after 35 min. The degradation was pH dependent, and a concentration-dependent inhibition was observed when aprotinin, a proteinase inhibitor, was preincubated with contents from the ileum. No degradation of AVP, dDAVP, or oxytocin analogues was observed in the mucosa homogenate from the stomach. The peptides were found to be rather slowly degraded by intestinal microvilli membranes and colonic and rectal plasma membranes. This degradation occurred essentially when reduced glutathione 10(-4) M was added to the incubations. In conclusion, the major enzymatic barrier to intestinal absorption of OT, VP, and their analogues is present in the intestinal juice and not in the mucosa, which, however, constitutes a major physical barrier to peptide transport.

Metabolism of vasopressin, oxytocin and their analogues [Mpa1, D-Arg8]-vasopressin (dDAVP) and [Mpa1, D-Tyr(Et)2, Thr4, Orn8]-oxytocin (antocin) in human kidney and liver homogenates.

Information regarding the metabolic fate of the neurohypophyseal hormones arginine-vasopressin (AVP), oxytocin (OT) and their analogues in man is practically non-existent. The aim of the present study was to investigate the stability of oxytocin, vasopressin and their analogues dDAVP and [Mpa1-D-Tyr2(Et), Thr4, Orn8]-oxytocin (antocin) in human renal microvilli brush border membranes and in human liver membranes. After incubation the extent of degradation of the peptides was determined by reversed phase high-performance liquid chromatography (HPLC). The degradation of both AVP and OT was rapid in the presence of glutathione and human renal microvilli membranes. AVP, as well as dDAVP, was stable when incubated with microvilli membranes without glutathione, while OT was metabolized. The metabolization of the oxytocin analogue, antocin, also varied with the presence of glutathione. While in the absence of glutathione a more lipophilic peak eluted, a more hydrophilic peak was observed with glutathione on HPLC. The lipophilic peak was found to coelute with the truncated analogue [Mpa1, D-Tyr2 (Et), Thr4, desOrn8, Gly9]-oxytocin. No degradation occurred when the peptides were incubated with liver membranes. However, when using crude, unpurified liver homogenate degradation occurred for all peptides except antocin. The degradation of AVP in the human unpurified liver homogenate was as rapid as in the renal microvilli membranes. Similarly, OT was more rapidly degraded in human kidney microvilli membranes in the presence of glutathione than in the human crude liver homogenate, when using equal amounts of protein in the incubations. Thus, the present investigation indicates the existence of two possible metabolic pathways, in kidney microvilli, one for OT, which did not require the presence of reduced glutathione, and one for AVP, which required the presence of reduced glutathione. Liver degradation, on the other hand, requires the hepatocytes.

Use of electron microscopic and immunogold labeling techniques to determine polyomavirus recombinant VP1 capsid-like particles entry into mouse 3T6 cell nucleus.

Murine polyomavirus major structural protein VP1 could assemble into capsid-like particles when expressed in the baculovirus system. The recombinant capsid-like particles that were purified by CsCl density gradient centrifugation were capable of packaging host DNA. Electron microscopic and immunogold labeling techniques were used to study the entry of these VP1 recombinant capsid-like particles into mouse 3T6 cells. It was found that these VP1 recombinant capsid-like particles, which lack polyomavirus minor structural proteins (VP2 and VP3), use the same mechanism to enter mouse 3T6 cell cytoplasm and nucleus as that used by native polyomavirus virions.

Long-term astigmatic changes after phacoemulsification with single-stitch, horizontal suture closure.

We analyzed postoperative corneal astigmatism in 32 eyes followed for three years after small incision phacoemulsification with a 4 mm scleral tunnel incision and a single-stitch, horizontal suture technique. Sutures were left intact postoperatively. Mean surgically induced cylinder was 0.63 diopters (D) at one day postoperatively, -0.01 D at one year, and -0.07 D at three years. A significant number of eyes showed an initial shift toward with-the-rule astigmatism. At one year, the axis had nearly returned to preoperative orientation without further against-the-rule shift after three years. An uncorrected visual acuity of 20/40 or better was found in 43.8% of the patients at one week postoperatively and in 62.5% at one and three years. Best corrected visual acuity of 20/40 or better was found in 62.5%, 90.6%, and 93.7%, respectively.

Retinal detachment after cataract extraction in myopic eyes.

PURPOSE: To determine the incidence of retinal detachment (RD) after cataract extraction in people 40 years of age or older with axial myopia (i.e., axial length > or = 25.5 mm). SETTING: Fifteen Danish eye clinics. METHODS: Two hundred forty-five eyes had cataract extraction performed at 15 eye clinics; 237 eyes had extracapsular cataract extraction (ECCE) and 8 eyes, intracapsular cataract extraction (ICCE). Postoperative data were reported by the practicing ophthalmologists. Mean follow-up was 27 months (range 14 to 32 months). RESULTS: Five RDs occurred in the 245 eyes (2.0%). Excluding the ICCE cases and the two cases of combined cornea transplantation and ECCE, RD occurred in 4 of the 235 eyes that had ECCE (1.7%). The incidence after ECCE with posterior chamber lens implantation was 1.4%. Complete postoperative status was reported on 158 eyes. Forty-eight eyes (30.4%) had a neodymium:YAG capsulotomy and 3 (6.0%) developed an RD 1, 3.5, and 21 months after the capsulotomy. CONCLUSION: The RD incidence after ECCE with posterior chamber lens implantation was low but higher than that in unselected populations. The incidence increased after laser capsulotomy.

Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies.

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.