Relative safety of single versus divided dose imipramine in adolescent major depression.
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Biomedical subjects
Publications and source records attributed to M Davies.
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Hypophosphataemic rickets is commonly an X linked dominant hereditary disorder associated with a renal tubular defect in phosphate transport and bone deformities. The gene causing this disorder has been mapped to Xp22.31----p21.3 by using cloned human X chromosome sequences identifying restriction fragment length polymorphisms (RFLPs) in linkage studies of affected families. The hypophosphataemic rickets gene locus (HPDR) was previously mapped distal to the X linked polymorphic locus DXS41 (99.6) but its position in relation to the distal loci DXS43 (D2) and DXS85 (782) was not established. In order to obtain a precise mapping of the disease locus in relation to these genetic loci, additional affected families informative for these X linked markers have been investigated. The combined results from the two studies have established linkage with the loci DXS41 (99.6) and DXS43 (D2); peak lod score for DXS41 (99.6) = 7.35, theta = 0.09, and peak lod score for DXS43 (D2) = 4.77, theta = 0.16. Multilocus linkage analysis mapped the hypophosphataemic rickets gene distal to the DXS41 (99.6) locus and proximal to the DXS43 (D2) locus, thereby revealing two bridging genetic markers for the disease.
The overnight effluent obtained from 62 patients undergoing CAPD was examined for IgG, C3 and C4 concentrations and for opsonic activity against S. epidermidis using polymorphonuclear leucocyte phagocytosis and luminol-dependent. chemiluminescence. There was a negative correlation between IgG and the age of the patient, but no relationship between IgG, C3 and C4, time on CAPD, or clinical diagnosis. Forty-eight of these patients were followed up for 6 months and 37 for a full year. An effluent IgG concentration of less than 0.105 g/l was associated with a significantly greater risk of infection with S. epidermidis during the study period. Comparing 'high' and 'low' values of C3 and C4, and using phagocytosis and chemiluminescence as measures of opsonic activity there were significant differences in the frequency of S. epidermidis peritonitis between the two groups during the follow up periods. No patient with high values of both IgG and C3 had S. epidermidis peritonitis during 12 months of study. Opsonic activity was both immunoglobulin and complement dependent. The latter activity involved both the classical and alternative complement pathways. These results suggest that routine screening of dialysate for IgG and C3 concentrations may be of prognostic value.
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Two patients with extensive tumoral calcinosis were treated with aluminium hydroxide. Initial metabolic studies showed positive calcium and phosphorus balances which became negative with aluminium hydroxide treatment. One subject, who had renal impairment, developed transient hypercalcaemia, parathyroid suppression, low levels of 1,25-dihydroxyvitamin D and calcium malabsorption during treatment with aluminium hydroxide. The second patient developed calcium malabsorption due to vitamin D deficiency. When she was replete with vitamin D there were supranormal levels of 1,25-(OH)2D in the serum and enhanced calcium absorption during treatment with aluminium hydroxide. Both subjects developed hypercalciuria and there was dissolution of many of the calcific tumours. The patient with renal impairment accumulated aluminium in the bone.
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We have examined the ability of rat mesangial cells to regulate neutral proteinase production in vitro. Mesangial cells constitutively produced gelatinase when cultured in serum-free medium, and enzyme production by these cells was inhibited by cycloheximide. Coculture with thioglycollate-elicited rat peritoneal macrophages resulted in enhanced gelatinase production. The increase in enzyme released correlated directly with the number of macrophages added. Conditioned medium from LPS-activated peritoneal macrophages also enhanced gelatinase production in a dose-dependent manner. Fractionation of these macrophage supernatants on Sephacryl S-200 revealed a predominant fraction of gelatinase-enhancing activity in a m.w. range between 10,000 and 20,000. These data suggested that the enhanced mesangial cell gelatinase production was mediated through the action of interleukin 1. This was confirmed by the finding that purified interleukin 1, prepared from LPS-stimulated rat peritoneal macrophages, stimulated mesangial cells to secrete gelatinase in a dose-dependent manner. These findings may be of significance in the understanding of the pro-inflammatory role of macrophages in immune-mediated glomerulonephritis.
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The antinociceptive effect of acute administration of 5-HT receptor agonists and agents releasing 5-HT from neuronal terminals was studied in rats by using the hot-plate, tail-flick and shock-titration tests. Noradrenaline depletion by the noradrenaline-neurotoxin N-2-chloroethyl-N-ethyl-2-bromo-benzylamine hydrochloride (DSP4, 2 X 50 mg/kg) blocked the analgesia induced by the 5-hydroxytryptamine (5-HT) receptor agonists 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and quipazine, as well as that induced by acute release of 5-HT by p-chloroamphetamine (PCA) and increased 5-HT synthesis by 5-hydroxytryptophan (5-HTP). Analgesia in the tail-flick test was partly blocked by both methergoline and mianserin, whereas the analgesic effects of 5-MeODMT in the hot-plate and shock-titration tests were unaffected by the 5-HT antagonists. In the shock-titration test it was found that the DSP4-pretreated animals were made hyperalgesic by acute 5-MeODMT, and this hyperalgesia was blocked by both mianserin and methergoline, implying that this effect was 5-HT receptor mediated. It is therefore concluded that a functional central noradrenergic system is required for eliciting 5-HT receptor mediated analgesia, and that these interactions, at least in part, are probably spinally located.
We examined sequelae of depressive mood, experienced at ages 15 to 16 years, nine years later at ages 24 to 25 years in subjects formerly enrolled in New York State public high schools. Feelings of dysphoria in adolescence predict most strongly a similar experience in adulthood. Such feelings also predict psychiatric hospitalization for women but not for men, at least up to the period we investigated. In addition, adolescent depression is associated with heavy cigarette smoking, increased use of minor prescription tranquilizers (among women), more deviant activities and accidents as young adults, and selective effects on interpersonal relationships. The long-term effects of adolescent depression manifest themselves in a reduced ability to establish an intimate relationship with a member of the opposite sex rather than the ability to maintain a circle of male and female friends. The distance from spouse (or partner) repeats within the marital dyad the lack of closeness to parents experienced in adolescence. Dysphoric mood seems to be associated with a deficiency to establish close interpersonal relationships within the family that expresses itself differently at different stages of the life cycle: toward parents in adolescence, and toward spouses and parents in young adulthood.
To examine the consequences of adolescent drug use on the psychosocial and health functioning of young adults, we followed up 1004 young men and women from age 15 or 16 years to age 25 years. The use of four different classes of drugs was examined: cigarettes, alcohol, marijuana, and other illicit drugs. Twenty outcomes were examined, including continuity of participation in work and in family roles, level of education, delinquent activities, self-reported health and psychological symptoms, and use of five drug classes in early adulthood (including prescribed psychoactive medications). The effects of marijuana and of other illicit drugs could not be disentangled, so these drugs were treated as a single class. Controlling for initial individual differences in adolescence, use of the three major drug classes between adolescence and early adulthood affected most of the outcomes examined; most strongly continued use of the same substance. Unique drug effects included those of illicit drugs on increased delinquency, unemployment, divorce, and abortions, and of cigarettes on lowered psychological mood. Illicit drugs predicted drug-related health problems, whereas cigarette use predicted increased breathing difficulties.
Eleven families with X-linked dominant hypophosphataemic rickets (HPDR) have been typed for a series of X chromosome markers. Linkage with probe 99.6 (DXS41) was demonstrated with a peak lod score of 4.82 at 10% recombination. Multilocus linkage analysis showed that HPDR maps distal to 99.6; this probe has previously been located at Xp22.31-p21.3 by in situ hybridisation. In the mouse hypophosphataemia (Hyp) maps to the distal part of the X chromosome; our location in man is consistent with a scheme which relates the mouse and human X chromosomes by two rearrangements. No marker has yet been found which shows no recombination with HPDR.
By the manipulation of the fractionation conditions of a series of protein A affinity columns it was possible to separate the antibody and antigen components of the immune complexes formed in the serum during normal human pregnancy. The two components were partially characterised in order to determine that they were separate biological entities. The IgG immunoglobulin component possessed antibody activity directed against the outer layer of the placenta, the syncytiotrophoblast. The antigen component was of apparent syncytiotrophoblast origin and consisted of a protein with two major polypeptides of Mr 63 kDaltons and 31 kDaltons.
The possible myocardial protective effect of oral propranolol in combination with potassium cardioplegia and hypothermia was investigated in 30 greyhounds, divided into 2 sub-groups, by determining the changes in myocardial ATP and CP levels, ultrastructural changes and the changes in hemodynamics after a 2-hour period of myocardial ischemia. In group 1, in animals with multiple doses of cardioplegia during the 2-hour ischemic period, preoperative treatment with propranolol did not have a significant myocardial protective effect. In group 2, in animals with a single dose of cardioplegia, during the 2-hour ischemic period, propranolol resulted in a trend of improved survival, although the myocardial ATP and CP levels were the same in both sub-groups. In addition, the multiple doses of cardioplegia in group 1 caused increased subcellular edema in the myocardium. This study suggests that oral propranolol treatment may provide additional myocardial protection during ischemic periods when used with potassium cardioplegia and hypothermia. The mechanism of this effect is not established, but could relate to reduced transmembrane calcium influx.
The seasonal changes in the biochemical indices of vitamin D nutrition have been measured in elderly people with differing requirements for institutionalized care. Residents of local authority homes (LAH) showed an increase in serum 25-hydroxyvitamin D3 [25(OH)D3] between spring and autumn (means 14-17 nmol/l, P less than 0.002). No significant seasonal changes were seen in patients on long-stay wards [(GW) serum 25(OH)D3 9.5 and 9.5 nmol/l] and in day-hospital attenders [(GDH) 25 and 26.8 nmol/l]. Significant differences (P less than 0.02 to P less than 0.0001) were found between the mean serum 25(OH)D3 amongst the three groups. A significant linear relationship (r = 0.84, P = 0.036) was found between mean serum 25-hydroxyvitamin D2[25(OH)D2] and dietary vitamin D2. The intake of vitamin D was suboptimal in all groups. The incidence of 25-hydroxyvitamin D deficiency [25(OH)D less than 12.5 nmol/l] varied from 11.7% of residents in LAH in autumn to 47% of GW patients in spring; but hypocalcaemia occurred less often (LAH 1.3% in autumn, GW 4.7% in spring). The diet assumes a greater role in protecting against vitamin D deficiency when the total 25(OH)D is low. Because most diets contain insufficient amounts of vitamin D, elderly institutionalized people will remain at high risk of developing vitamin D deficiency unless specific preventative measures are adopted.
Thirty-four adolescents with mean age 14.25 years who met RDC criteria for major depressive disorder as assessed with the K-SADS, were treated for 6 weeks on a fixed schedule of imipramine hydrochloride titrated to a dosage of 5.0 mg/kg/day except as limited by side effects. Mean dose was 246 mg/day (4.5 mg/kg/day). In spite of good indications of compliance with treatment only 44% of the adolescents improved to the level of no or only slight depressed mood or anhedonia, though most had less depressive symptomatology at the end of treatment. There was neither a linear nor curvilinear relationship between total plasma level of IMI plus DMI and clinical response, despite a wide range of both plasma level (77 ng/ml to 986 ng/ml) and outcome. Adolescents with associated separation anxiety had significantly poorer response to treatment of their depressive disorder than those with major depression alone. Poor response was also weakly associated with being female, having endogenous subtype of depression, and having higher plasma IMI (but not DMI) level. In the context of similar studies of IMI on depression in other age groups, it is hypothesized that high levels of sex hormones during adolescence and young adulthood may interfere with IMI's antidepressant effects. It is concluded that other types of antidepressants should be tested in adolescents with major depression.