Threshold and subthreshold generalized anxiety disorder among US adolescents: prevalence, sociodemographic, and clinical characteristics.

BACKGROUND: Threshold and subthreshold forms of generalized anxiety disorder (GAD) are highly prevalent and impairing conditions among adults. However, there are few general population studies that have examined these conditions during the early life course. The primary objectives of this study were to: (1) examine the prevalence, and sociodemographic and clinical characteristics of threshold and subthreshold forms of GAD in a nationally representative sample of US youth; and (2) test differences in sociodemographic and clinical characteristics between threshold and subthreshold forms of the disorder. METHOD: The National Comorbidity Survey-Adolescent Supplement is a nationally representative face-to-face survey of 10,123 adolescents 13 to 18 years of age in the continental USA. RESULTS: Approximately 3% of adolescents met criteria for threshold GAD. Reducing the required duration from 6 months to 3 months resulted in a 65.7% increase in prevalence (5.0%); further relaxing the uncontrollability criterion led to an additional 20.7% increase in prevalence (6.1%). Adolescents with all forms of GAD displayed a recurrent clinical course marked by substantial impairment and co-morbidity with other psychiatric disorders. There were few significant differences in sociodemographic and clinical characteristics between threshold and subthreshold cases of GAD. Results also revealed age-related differences in the associated symptoms and clinical course of GAD. CONCLUSIONS: Findings demonstrate the clinical significance of subthreshold forms of GAD among adolescent youth, highlighting the continuous nature of the GAD construct. Age-related differences in the associated symptoms and clinical course of GAD provide further support for criteria that capture variation in clinical features across development.

Biochemical evidence that acetylcholine release from cholinergic nerve terminals is mostly vesicular.

The nature of the intraterminal compartments from which acetylcholine (ACh) is released following presynaptic stimulation was investigated. This was pursued by examining the effects of the anticholinergic drug 2-(4-phenylpiperidino)cyclohexanol (AH5183) on the release of newly synthesized [3H]ACh and of endogenous ACh from purified cholinergic nerve terminals (synaptosomes) which were isolated from the electric organs of Torpedo. Preincubation of the synaptosomes, with AH5183 (1-10 microM), does not affect either the intraterminal synthesis of [3H]ACh or the uptake of its precursors, but results in a marked inhibition (85%) of the release of the newly synthesized [3H]ACh. However, when AH5183 is added following the accumulation of [3H]ACh in the nerve terminals, it does not affect [3H]ACh release. AH5183 also has no effect on the release of preformed endogenous ACh. These findings, together with the previous in vitro demonstrations that AH5183 is a potent inhibitor of ACh uptake into isolated cholinergic vesicles, suggest that most of the synaptosomal ACh is secreted by a vesicular mechanism.

Isolation of a beta 2-glycoprotein from human serum after precipitation with dextran sulfate and manganese chloride.

A new procedure was developed which affords isolation from among the euglobulins of human serum a beta 2-glycoprotein with a high degree of immunological and electrophoretic homogeneity. The isolated protein displays specific binding affinity for the activated form of the C4 component (C4b), and was identified by immunological and physico-chemical criteria as the C4 binding protein. The isolation procedure comprises the following steps: precipitation of euglobulins from serum at pH 5.5 and low ionic strength; precipitation of beta-lipoproteins from the redissolved precipitate with dextran sulfate and CaCl2; precipitation of a fraction of the lipoprotein-free euglobulins with dextran sulfate and MnCl2; redissolution of the precipitate and eventually chromatography on Sepharose 4B. The overall yield was between 15 and 20 per cent. The final product, devoid of immunologically detectable protein contaminants, was a homogeneous proline-rich monomeric beta 2-glycoprotein made up of eight disulfide-bonded polypeptide chains of the same molecular weight 63,000 +/- 3,000. Under non-reducing conditions, the molecular weight of both the native and the SDS-treated protein was 490,000 +/- 25,000. A monospecific antiserum to the isolated protein was raised in rabbits and used for the quantitation of the protein in sera of normal fasting donors; a mean concentration of 25 mg per 100 ml of serum (1 SD: 5) was established.

Rapid method for the isolation of two purified subfractions of high density lipoproteins by differential dextran sulfate-magnesium chloride precipitation.

We describe a rapid and reliable three-step precipitation procedure for the isolation of large amounts of the two major components of high density lipoproteins (HDL) in human serum. Precipitation was accomplished by means of dextran sulfate (DS) of mol. wt. 500,000 and MgCl2. First, all apoB-associated lipoproteins of any density were selectively precipitated with critical concentrations of reagents. Secondly, a subfraction of HDL was differentially precipitated from the apoB-depleted serum by increasing the concentration of both reagents. Eventually, the bulk of the remainder of HDL was precipitated by lowering the pH to 5.4. According to the precipitation patterns and the density profiles, the DS-Mg procedure provides a clear differentiation between the two HDL components. According to the compositional criteria and the ultracentrifugal characteristics, the two polyanion-precipitated subclasses are very similar to, if not identical with, the two density subclasses, the lighter HDL2 and the heavier HDL3, isolated by preparative ultracentrifugation after apoB-containing lipoproteins had been removed.

Metabolism of arachidonic acid and prostaglandins in the Torpedo electric organ: modulation by the presynaptic muscarinic acetylcholine receptor.

We have found that Torpedo electric organ readily synthesizes prostaglandin E2 from both exogenous and endogenous arachidonate and that activation of the presynaptic muscarinic acetylcholine receptor increases the rate of prostaglandin E2 synthesis by inducing the release of tissue arachidonate from its phospholipid pools. The incorporation of radiolabeled arachidonate into tissue phospholipids is slow and Ca2+ independent. However, the electric organ slices readily oxidize the externally added, radiolabeled arachidonate via the cyclo-oxygenase pathway, with prostaglandin E2 being the major product (22 +/- 4% of the initial radioactivity). This process is not affected by either Ca2+ or mepacrine. Torpedo electric organ slices also synthesize prostaglandin E2 from endogenous substrates, and release it into the medium. This process, however, is enhanced by Ca2+ and inhibited by mepacrine. Activation of the Torpedo muscarinic acetylcholine receptor by the agonist oxotremorine results in a dose-dependent atropine-sensitive increase in the synthesis of prostaglandin E2 from endogenous tissue substrates and in the concomitant release of arachidonate into the medium. By contrast, oxotremorine has no effect on either the formation of [14C]prostaglandin E2 from exogenous arachidonate, the incorporation of radiolabeled arachidonate into tissue phospholipids or its liberation from prelabeled slices. These results suggest that activation of the muscarinic acetylcholine receptor induces lipolysis which results in the liberation of endogenous arachidonate and its subsequent conversion to prostaglandin E2.

Inhibition of HIV-1 replication by newly developed adamantane-containing polyanionic agents.

Newly developed antiviral compounds consisting of an adamantane derivative chemically linked to a water-soluble polyanionic matrix were shown to inhibit HIV-1 infection in lymphoblastoid cells, HeLa CD4+ beta-galactosidase (MAGI) cells and macrophages. The effect of the compounds was recorded by measuring viral reverse transcriptase activity and p24 by ELISA in culture supernatant and by immunoblotting of cell lysates. In this paper we describe the data obtained with one of the most promising compounds, Amant. Amant was not toxic for the host cells at concentrations as high as 1 mg/ml. The inhibition of HIV-1 replication in MT-4 and MAGI cells was observed when Amant was added either before infection or with the virus (0 h of infection), and was expressed even when the compound added at 0 h was removed 1.5 h after infection. Its inhibitory concentration (IC50) against HIV-1 and HIV-2 replication was 2-6 and 93 microg/ml, respectively. The anti-HIV-1 effect of the compound was gradually decreased when it was added 1 and 2 h post infection, and no inhibition was observed when the compound was added 4 h after infection, suggesting that the compound as a membranotropic drug blocks an early step of replication. It completely prevented the transport of Gag proteins into the nuclei. Pretreatment of the virus with Amant did not reduce its infectious activity. The classical adamantane derivatives amantadine and rimantadine hydrochloride did not inhibit HIV replication.

Distribution of HDL2 and HDL3 in a random population of healthy French males and females--evaluation by a two-step precipitation procedure.

A rapid and reliable method for the determination of HDL2 and HDL3 cholesterol is described. The Apo B containing fractions (VLDL, IDL, LDL) were precipitated by addition of dextran sulfate (Mr 500,000) to 2 mmol/l final concentration followed by MgCl2 to a final concentration of 0.05 mol/l. The supernatant, was brought to 6 mmol/l dextran sulfate and 0.250 mol/l MgCl2 to precipitate HDL2. Cholesterol determination on total serum and both supernatants yielded the concentrations of Apo B-associated cholesterol, total HDL, HDL2 and HDL3 cholesterol. The application of this technique to a random population of healthy French people gave HDL-cholesterol values of 1.35 and 1.54 mmol.l-1, respectively, in 93 males and 95 females (p less than 0.001). All of the difference was attributable to HDL2 (0.43 vs 0.65 mmol.l-1, p less than 0.001) while HDL3 were almost identical at 0.92 and 0.91 nmol.l-1. These values are in good agreement with previously reported figures for French individuals, but markedly higher in males than values reported from North America.

Interaction of heparin with low density lipoproteins. Formation of soluble high molecular weight complexes.

The electrophoretic pattern of low density protein (LDL) in heparinized human serum was analyzed by means of molecular-sieve electrophoresis in polyacrylamide gradient gels. While increasing the electrophoretic mobility of LDL in nonsieving gels (agarose), heparin markedly decreases the electrophoretic mobility of LDL in polyacrylamide gels. This slowing down reflects the formation of large polymers where individual lipoprotein molecules are linked by heparin bridges.

[Jacuzzi-immersion for obstetric analgesia].

The effect of immersion in a jacuzzi in relieving labor pains, and on cervical dilatation was examined in 40 parturients. They were immersed in the jacuzzi during labor for an average of 25.5 minutes. Labor pains decreased during immersion by 2.59 degrees (scale of 0-10) compared with an average increase in labor pains of 0.25 degrees in 40 control women who were not immersed (p < 0.01). The cervical opening increased during immersion by an average of 1.5 cm in the test group, compared with 0.3 cm in the controls (p < 0.01). Immersion in a jacuzzi during labor is apparently associated with analgesia and accelerated cervical dilatation.

[Placenta accreta with placenta previa after previous cesarean sections--a growing danger in modern obstetrics].

The increased rate of cesarean sections in recent decades has brought with it an increase in the frequency of placenta accreta. There are direct correlations between previous cesarean deliveries and also maternal age, with the risk of placenta accreta. There is also a direct correlation between placenta accreta and placenta previa. The risk of placenta accreta in women who have had placenta previa is 2% for those younger than 35 years and with no history of uterine surgery. The risk increases to 39% for those over 35 who have had 2 or more cesarean sections. We present 3 cases of placenta accreta admitted in 15 months, all of whom had a history of cesarean sections. The frequency of placenta accreta in our hospital is 1:1,579 deliveries, in line with the 1:1,420 in the literature. We consider hysterectomy the treatment of choice for this serious complication. When performing a cesarean in cases of placenta previa with a history of cesarean sections, the possibility of placenta accreta should be considered.

[Operative laparoscopy in pregnancy].

The development of laparoscopic surgery in gynecology and general surgery has greatly advanced over the past decade, and recently has been successfully performed in pregnancy. In the English literature we found that of the 518 cases reported (mean age 32 years) the most common was for cholecystectomy (45%), followed by operations on the adnexae (34%), appendectomy (15%) and others (6%). To these we add 3 cases of cholecystectomy and 1 of an adnexal tumor. Of all the reported cases, 33% were performed in the 1st trimester, 56% in the 2nd and 11% in the 3rd. This review demonstrates a definite trend to laparoscopy in pregnancy. It appears to be safe when performed by experienced surgeons, but further studies addressing safety of laparoscopic surgery during pregnancy are needed to reach definitive conclusions.

[Polysulfates, anionic detergents, sodium phosphotungstate and electrophoretic mobility of plasmatic proteins]. / Polysulfates, détergents anioniques, phosphotungstate de sodium et mobilité électrophorétique des protéines plasmatiques.

Anions with strong electro-negative charges, like sulphuric esters of polysaccharides (heparin, dextran sulphate M.W. 15 00), the sodium salt of polyanethol sulfonic acid (liquoid, Roche), anionic detergents (sodium dodecylsulphate, sodium oleate, sodium deoxycholate), and the sodium salt of phosphotungstic acid were added to human serum or citrated plasma. For each compound several final concentrations were adopted, the highest being 4%. By using microimmunoelectrophoresis and numerous specific antisera against human plasma proteins, it was demonstrated that at pH 8.60 anions increase electrophoretic mobility of the following antigens: lipoproteins alpha and beta; fibrinogen; beta 2-glycoprotein I; beta 2-glycoprotein II ; antithrombin III. All reagents utilized do not react with all these proteins; for instance, only detergents accelerate the migration rate of a lipoproteins. Besides, depending on the protein, this or that reagent may be the most active. Thus, in the polysulphate group, heparin has the highest affinity for antithrombin III, liquoid for fibrinogen and dextran sulphate for beta 2-glycoprotein I.

New directions for the management of the Canadian immigration program.

PIP: The Canadian system for managing immigration is influenced by two recently enacted measures, the Bill C-86 and the Immigration Plan for 1993. Over the last few years, there has been a shift from the view that independent immigration benefits Canada through scale economies to the view that independent migrants must contribute to higher productivity through their skills, knowledge, and experience. The new view of immigration is consistent with the new economic theories of higher productivity and growth through use of knowledge and creativity in producing small runs of specialized, tailored products. During 1990-92 Canadian immigrants were concentrated within the Family class and to a lesser extent as Refugees, Independent and Assisted Relative Groups, and Business dependents. The Bill C-86 allows for limits among classes of immigrants and selection based on either a first-come first-served basis or a comparative basis. Changes occurred in the selection criteria for skilled workers as a first stage in implementation of the bill. The 1993 Plan established numerical estimates that still favored the Family class but increased the number in the Independent, Relative, and Business classes and Retirees. Immigrants applying for the Independent, Relative, and Business classes are assessed based on their intended occupation, the placement of intended occupation on the Designated Occupations List of shortages, and a validated job offer in Canada. Meeting any 1 of the 3 criteria enables an immigrant to be assessed further on 8 other criteria (intended occupation, job experience in intended occupation, specific vocational preparation, arranged employment, education, language, age, and personal suitability). Each criteria is assessed points, and 70 out of 100 points are required for admission. Further refinements have been made to increase the number of points accrued to Specific Vocational Preparation for higher skilled occupations and to decrease the number of points for assisted relatives. The number of occupations on the General List was increased several times, and points for the Demographic factors were increased. Refinements were introduced later for increasing the abilities in language and education. No points were given for less than a secondary education or weak language skills.^ieng

Purification of rabbit anti-human fibrinogen antibodies cross reactivity of mammalian fibrinogen.

A simple isolation procedure of highly purified and unaltered rabbit antibodies to human fibrinogen is described. The method used is based upon the preferential adsorption of fibrinogen by barium sulfate at acid pH. After redissolution of the specific precipitate and dissociation of the antigen-antibody complexes at pH 2.4, the fibrinogen is removed by adsorption on barium sulfate, while the antibody protein stays in solution. BaSO4 is eliminated by centrifugation and the supernatant is neutralized and concentrated by ammonium sulfate fractionation (40% saturation). A concentrated solution of specific anti-fibrinogen antibodies is thus obtained; the latter can be used to prepare, by selective immunprecipitation, a fibrinogen free plasma, and to analyze precipitin patterns in cross reacting systems.

[Specific rabbit abtiserum against human chylomicrons and very low density lipoproteins]. / Immunsérum spécifique de lapin contre les chylomicrons et les lipoprotéines de trés faible densité du sérum humain

Rabbits were immunized by repeated intravenous injections of large amounts of chylomicrons plus VLDL isolated from human lipemic plasmas. The antisera were absorbed usccessively with lipoprotein free serum, HDL and LDL2. The absorbed antisera still precipitate chylomicrons and VLDL from sera of normal and hyperlipemic subjects (post-absorptive donors and fasting patients with type IV and type V hyperlipoproteinemia). By gel diffusion methods (immunoelectrophoresis and double diffusion in two dimensions), the antisera reveal a single precipitin line which stains better for lipid than for protein. This line is pronounced in VLDL-rich sera and absent in VLDL-free sera. The antisera react with chylomicrons plus VLDL delipidated by extraction with ethanol/diethyl ether; this shows that the antigenic site is an apoprotein; in contrast to apoprotein C, this apoprotein appears to be unique to the triglyceride-rich lipoproteins.

[Detergents and precipitation of serum lipoproteins by antisera (author's transl)]. / Détergents et précipitation des lipoprotéines sériques par des immunsérums

By using gel diffusion methods, it was shown that during immunoelectrophoresis and double diffusion in two dimensions, anionic detergents (sodium oleate, sodium desoxycholate, sodium lauryl-sulfate and sodium decyl-sulfate), added to human serum at the final concentration of 0.5%, do not prevent the formation of an insoluble antigen-antibody complex (precipitation line) when specific antibodies react with serum lipoproteins: LDL, HDL and VLDL. In spite of the presence of anionic detergents, the antigen-antibody interaction in gel occurs even if the amount of lipoproteins in serum was highly reduced. On the contrary, the non ionic detergent tween 80, has a strong inhibitory effect on the specific precipitation of lipoproteins, especially in the case of HDL.