Measurements of fetal head compression pressure during bearing down and their relationship to the condition of the newborn

Fetal head compression pressure (FHCP) and its clinical importance has been investigated in a group of 46 spontaneous births. Measurement of FHCP was facilitated using a compression transducer positioned between the fetal head and the wall of the birth canal. This method not only constitutes a means of quantitating the forces acting directly on the fetal head, but also provides information about the intracranial pressure generated during delivery. The latter extrapolation is based on the principle of applanation. The technique provides an objective and reliable estimate of intracranial strain and therefore a means of comparing the forces generated under different delivery modes. The condition of the same neonates at birth was assessed using umbilical artery pH, Apgar score, neurobehavioral testing and fundoscopic examination. The mean amplitude of FHCP in the different deliveries ranged from 38 to 390 mmHg (5-52 kPa) with an overall mean of 157.9 mmHg (21.1 kPa). The study indicated that the appearance of retinal hemorrhages in the newborn cannot be explained by exposure of the fetal head to abnormally high compression during birth. Other explanations must be sought for infants with a neurobehavioral deficit, reduced Apgar score, or umbilical artery acidosis at birth. It is concluded that a relatively short period of high FHCP has no obvious consequences for fetal well-being, at least within the limits described in the present report.     

Neonatal Exposure to a Combination of N-Methyl-d-aspartate and γ-Aminobutyric Acid Type A Receptor Anesthetic Agents Potentiates Apoptotic Neurodegeneration and Persistent Behavioral Deficits

Background: During the brain growth spurt, the brain develops and modifies rapidly. In rodents this period is neonatal, spanning the first weeks of life, whereas in humans it begins during the third trimester and continues 2 yr. This study examined whether different anesthetic agents, alone and in combination, administered to neonate mice, can trigger apoptosis and whether behavioral deficits occur later in adulthood.

Methods: Ten-day-old mice were injected subcutaneously with ketamine (25 mg/kg), thiopental (5 mg/kg or 25 mg/kg), propofol (10 mg/kg or 60 mg/kg), a combination of ketamine (25 mg/kg) and thiopental (5 mg/kg), a combination of ketamine (25 mg/kg) and propofol (10 mg/kg), or control (saline). Fluoro-Jade staining revealed neurodegeneration 24 h after treatment. The behavioral tests-spontaneous behavior, radial arm maze, and elevated plus maze (before and after anxiolytic)-were conducted on mice aged 55-70 days.

Results: Coadministration of ketamine plus propofol or ketamine plus thiopental or a high dose of propofol alone significantly triggered apoptosis. Mice exposed to a combination of anesthetic agents or ketamine alone displayed disrupted spontaneous activity and learning. The anxiolytic action of diazepam was less effective when given to adult mice that were neonatally exposed to propofol.     

Hippocampal and neocortical gamma oscillations predict memory formation in humans

Functional magnetic resonance imaging (fMRI) of the human brain has shown that the hippocampus and the left temporal and frontal cortices play a key role in the formation of new verbal memories. We recorded electrical activity from 2349 surgically implanted intracranial electrodes in epilepsy patients while they studied and later recalled lists of common words. Using these recordings, we demonstrate that gamma oscillations (44-64 Hz) in the hippocampus and the left temporal and frontal cortices predict successful encoding of new verbal memories. This increase in gamma oscillations was not seen in other frequency bands, whose activity generally decreased during successful memory formation. These findings identify a role for gamma oscillations in verbal memory formation with the hippocampus and the left temporal and frontal cortices, the same regions implicated using noninvasive fMRI recording methods.     

Long-term effects of Internet-delivered cognitive behavioral therapy for depression in primary care – the PRIM-NET controlled trial

Objective: Internet-delivered cognitive behavioral therapy (ICBT) is recommended as an efficient treatment alternative for depression in primary care. However, only few previous studies have been conducted at primary care centers (PCCs). We evaluated long-term effects of ICBT treatment for depression compared to treatment as usual (TAU) in primary care settings.

Design: Randomized controlled trial.

Setting: Patients were enrolled at16 PCCs in south-west Sweden.

Participants: Patients attending PCCs and diagnosed with depression (n?=?90).

Interventions: Patients were assessed by a primary care psychologist/psychotherapist and randomized to ICBT or TAU. The ICBT included an ICBT program consisting of seven modules and weekly therapist e-mail or telephone support during the 3-month treatment period.

Main outcome measures: Questionnaires on depressive symptoms (BDI-II), quality of life (EQ-5D) and psychological distress (GHQ-12) were administered at baseline, with follow-ups at 3, 6 and 12 months. Antidepressants and sedatives use, sick leave and PCC contacts were registered.

Results: Intra-individual change in depressive symptoms did not differ between the ICBT group and the TAU group during the treatment period or across the follow-up periods. At 3-month follow-up, significantly fewer patients in ICBT were on antidepressants. However, the difference leveled out at later follow-ups. There were no differences between the groups concerning psychological distress, sick leave or quality of life, except for a larger improvement in quality of life in the TAU group during the 0- to 6-month period.

Conclusions: ICBT with weekly minimal therapist support in primary care can be equally effective as TAU among depressed patients also over a 12-month period.

Clinical trial registration: The trial was registered in the Swedish Registry, researchweb.org, ID number 30511.     

Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years

OBJECTIVE: Postmenopausal women are at increased risk of primary hyperparathyroidism (pHPT). Secondary dyslipidaemia in pHPT has attracted little attention, although morbidity and mortality associated with cardiovascular diseases have been reported to be increased in these patients. DESIGN: A population-based screening programme was used to recruit postmenopausal women with mild, asymptomatic pHPT (mean serum calcium 2.57 +/- 0.12 mmol/l) and matched controls. MEASUREMENTS AND PATIENTS: Serum lipids, lipoprotein fractions and influences of treatment for the parathyroid disease were studied in 87 case-control pairs (mean age 67 years), 69 of whom completed a 5-year follow-up period. RESULTS: pHPT was characterized by decreased serum high-density lipoprotein (HDL)-cholesterol, increased total triglycerides, very-low-density lipoprotein (VLDL)-triglycerides and VLDL-cholesterol levels and an elevated atherogenic index. The differences were more pronounced in the cases with serum parathyroid hormone levels in the normal range and were inversely correlated to the serum parathyroid hormone level. Parathyroidectomy, with or without additive hormone replacement therapy, normalized the dyslipidaemia. Five-year surveillance of pHPT without treatment was associated with a maintained increase in total triglycerides and the atherogenic index and a decrease in HDL-cholesterol levels. CONCLUSION: Proatherosclerotic dyslipidaemia characterizes mild pHPT and is effectively reversed by parathyroidectomy. As dyslipidaemia might contribute to the increased risk of cardiovascular diseases and death observed in pHPT, the findings favour operative intervention rather than conservative surveillance in mild, asymptomatic pHPT in postmenopausal females.     

Transmissibility of systemic amyloidosis by a prion-like mechanism

The generation of amyloid fibrils from an amyloidogenic polypeptide occurs by a nucleation-dependent process initiated in vitro by seeding the protein solution with preformed fibrils. This phenomenon is evidenced in vivo by the fact that amyloid protein A (AA) amyloidosis in mice is markedly accelerated when the animals are given, in addition to an inflammatory stimulus, an i.v. injection of protein extracted from AA amyloid-laden mouse tissue. Heretofore, the chemical nature of this "amyloid enhancing factor" (AEF) has not been definitively identified. Here we report that the active principle of AEF extracted from the spleen of mice with silver nitrate-induced AA amyloidosis was identified unequivocally as the AA fibril itself. Further, we demonstrated that this material was extremely potent, being active in doses <1 ng, and that it retained its biologic activity over a considerable length of time. Notably, the AEF was also effective when administered orally. Our studies have provided evidence that AA and perhaps other forms of amyloidosis are transmissible diseases, akin to the prion-associated disorders.     

A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes

OBJECTIVE: To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol. RESEARCH DESIGN AND METHODS: Individuals (n = 476) with HbA(1c) (A1C) 7.5-10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of < or =6.0 mmol/l (< or =108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C < or =7.0%, risk of hypoglycemia, and body weight. RESULTS: At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C 相似文献