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The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease.

This study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be important in the development of autoimmune thyroid disease. These factors were examined in (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone. Eight of 40 patients who were receiving lithium therapy were found to be positive for thyroid microsomal and/or thyroglobulin antibodies, compared to only 3/40 patients who were receiving some other form of treatment for their depression. Peripheral blood mononuclear cells from patients receiving lithium were found to have significantly reduced numbers of suppressor/cytotoxic T cells (P less than 0.05). In addition, suppressor T cells from these patients showed a significantly reduced response to stimulation with concanavalin A (P less than 0.01). These effects were greatest in patients found to be antibody positive. Increased B cell activity, as measured by increased IgG and IgM release following mitogen stimulation, was seen in patients receiving lithium and in those patients receiving other forms of treatment for their depression. This would suggest that the increase is a feature of primary affective disorders and is not due specifically to lithium treatment. It would appear from this study that lithium therapy induces antibody formation in susceptible individuals and this may ultimately lead to the development of thyroid disease.

Adult↗

Biochemical analysis of dermal connective tissue in subjects affected by primary uncomplicated varicose veins.

Biochemical analysis of dermal connective tissue was carried out in 14 subjects affected by primary uncomplicated varicose veins and 14 controls. Skin samples were taken, according to fixed criteria, from operation pieces of total mastectomy for breast cancer. The results suggest that the dermal tissue in these subjects is just thinner than that of controls, confirming previous similar clinical findings. The elective reduction of the collagen content observed, unassociated with changes of other components of the dermal connective tissue, brings evidence for a systemic biochemical defect of the extracellular matrix i.e. a collagen defect affecting the entire body structure and not only the varicose or pre-varicose veins of the lower limbs.

Adult↗

Autosomal primary immunodeficiencies affecting human bone marrow B-cell differentiation.

Since the initial report of X-linked agammaglobulinemia by Bruton, numerous autosomal primary immune deficiencies affecting early B-cell differentiation have been described in humans. The identification of these autosomal mutations has been facilitated by phenotype comparison with knockout mice. In mice, defects in B-cell development have been observed after disruption of genes encoding transcription factors, the interleukin-7 pathways as well as structural or signaling components of the pre-B-cell receptor. In general, the phenotypes of primary immune deficiencies in humans correlate with those observed in mutant mice, validating the use of the mouse model approach. In addition, we report a follow-up analysis of an autosomal primary deficiency in a young female patient born from consanguinous parents and characterized by the absence of pre-B and B-cell compartments. The patient's gene defect was identified as a cytosine insertion at the beginning of the CH1 exon of the Ig(mu) gene, resulting in a stop codon at position 48 and the absence of Ig(mu) chain expression. The precise phenotype of this patient is compared to other autosomal primary immunodeficiencies affecting humans and mice.

Amino Acid Sequence↗

Dentinoenamel junction area in primary teeth affected by Morquio's syndrome.

Separation of dentin from enamel in the dentinoenamel junction area was achieved in primary teeth affected by Morquio's syndrome. Enamel and dentin junctional surfaces were examined by means of scanning electron microscope. These two tissues were found to be separated by a layer of amorphous material. Recurrent treatment of the amorphous layer with NaOCl caused its gradual removal, exposing the rod tips on the enamel side and tubules on the dentin side. It is reasonable to suppose from this finding that the amorphous layer is rich in organic matrix. It is suggested that this amorphorus layer is analogous to the enamel-dentin membrane, that in this syndrome is only partially calcified.

Acid Etching, Dental↗

Evaluation of the outcome of patients admitted to the pediatric intensive care unit in Alexandria using the pediatric risk of mortality (PRISM) score.

The aim of this prospective study was to evaluate the use of pediatric risk of mortality (PRISM) score to predict the patient outcome in Alexandria Pediatric Intensive Care Unit (PICU). The study included all admissions to a tertiary care teaching hospital for 13 months. All patients were subjected to thorough history taking and clinical examination. The PRISM score was obtained within 8 h from admission (including 14 parameters with 34 variables). The primary affected system, referral site, number of organ failure on admission, length of hospital stay (LOS) and outcome of patients were recorded. The bed occupancy rate, turnover rate, average LOS, total and adjusted death rates were also recorded. Results showed that the total and adjusted mortality rates were 50 and 38 per cent respectively (n = 205/406 and 125/326, respectively). The mean PRISM score on admission was 26. Non-survivors showed a significantly higher mean score compared with survivors (36 vs. 17). Non-survivors compared with survivors, were significantly younger (12 vs. 23 months), had shorter LOS (3.8 vs. 5.3 days), three or four organ system failure on admission (77 vs. 25 per cent, and 9 vs. 0 per cent of patients) and had significantly higher percentage of sepsis syndrome and neurological diseases, as the primary affected system (20 vs. 10 per cent and 26 vs. 16 per cent). The PRISM score showed a significant positive correlation only with the number of organ failure on admission (r = 0.8104; p < 0.001). The cut-off point of survival was a PRISM score 26 with expected/observed ratio of 1.05 for non-survivors with 91.6 per cent accuracy. Multiple logistic regression analysis revealed that PRISM score, LOS, and the primary affected system were relevant predictors of patient outcome in PICU. In conclusion, the PRISM score is proved to be a good predictor of outcome for children admitted to a PICU with a cut-off point of 26. The mortality in the PICU is affected by LOS, primary system affected, and number of organ failure on admission.

Child, Preschool↗

N-methylnicotinamide excretion and affective disorders.

N-Methylnicotinamide urinary output is examined in 38 healthy volunteers, 52 patients with secondary affective disorders (SAD), 55 patients with primary affective disorders (PAD) and 46 healthy first-degree relatives of PAD patients. The results indicate (1) that in PAD patients and their first-degree relatives the frequency of low N1-MN excretion was significantly higher (P less than 0-001) than in healthy controls and in patients with secondary affective disorders, and (2) that PAD patients have a consistently low N1-MN output, at all times constant and independent of the clinical phases of the disease. These findings provide evidence that the low N1-MN levels may represent an index of a biological background linked to a high morbidity risk for primary affective disorders. The theoretical implications deriving from these data are briefly discussed.

Adjustment Disorders↗

Family history of suicidal behavior among suicide attempters.

Efforts to predict suicide and attempted suicide are hampered by their relative rarity on the one hand and the inadequate specificity of clinical characteristics and relevant antecedent events on the other; that is, these features are found widely among the nonsuicidal as well. In an effort to further understand these phenomena, the authors studied family history of suicidal behaviors (suicide, attempted suicide, and suicide threats) in 127 patients hospitalized following a suicide attempt. Patients with personality disorders (antisocial personality disorder, alcoholism, somatization disorder, and narcotic addiction), comprising 45 per cent of the sample, frequently reported a family history of these behaviors, most notably attempted suicide. Patients with primary affective disorder reported a family history of suicidal behaviors somewhat less often. The diagnoses grouped here as personality disorders (excepting alcoholism) contribute little to the suicide rate, while primary affective disorder contributes substantially. Although further data are needed, it is suggested that a family history of suicidal behavior in primary affective disorder should alert the clinician to heightened suicide risk, while a similar history in nonalcoholics with other psychiatric diagnoses is not particularly significant.

Adolescent↗

Psychotropic drugs and their relationship with psychopathology of affective disorders.

UNLABELLED: In this paper we discuss the relationship between the psychopathology of depressive behavior and the effectiveness of drugs affecting mood. Particular emphasis is given to the recent contribution of the authors (1975-1977) to the specific items of: 1. non-psychological validation of diagnosis of primary affective disorders 2. predictability of the response to antidepressant drugs 3. factors involved in the effectiveness of long-term lithium treatment. Key words: depression, primary affective disorders, secondary affective disorders, unipolar depression, bipolar depression, N1-methylnicotinamide, 3-methoxy-4-hydroxyphenylglycol, tricyclic antidepressant drugs, lithium prophylaxis, intraerythrocyte/plasma lithium ratio. ABBREVIATIONS: Cerebral spinal fluid (CSF); intraerythrocyte/plasma lithium ratio (Li ratio); 3-methoxy-4-hydroxyphenylglycol (MHPG): monoamine oxidase (MAO); morbidity risk (MR); N1-methylnicotinamide (N1-MN); norepinephrine (NE); primary affective disorders (PAD); secondary affective disorders (SAD).

Animals↗

The rho-115 mutation in transcription termination factor rho affects its primary polynucleotide binding site.

We have investigated the effect of the rho-115 mutation on the catalytic properties of the Escherichia coli termination protein, rho. Comparison of the primary and secondary polynucleotide binding sites activities reveals dramatic differences between the mutant and wild-type molecules. Wild-type rho must bind single-stranded polynucleotides to activate its nucleotide triphosphatase (NTPase) activity, and either poly(C), or poly(dC) plus oligo(C), will suffice. In contrast, attempted activation of the rho-115 NTPase with poly(C) in the presence of poly(dC) showed the latter to be a potent inhibitor. Inclusion of small oligonucleotides such as oligo(C) in the activation assay does not inhibit the poly(C)-induced NTPase reaction of either wild-type rho or rho-115. This would indicate, in the two polynucleotide binding site model for rho proposed by Richardson (Richardson, J.P. (1982) J. Biol. Chem. 251, 5760-5766), that the mutation in rho-115 affects the primary polynucleotide binding site. Transcription termination in vitro at the rho-dependent site trp t' showed dramatically reduced termination with rho-115 protein compared to wild-type rho. In the presence of rho-115, the transcript is longer and termination occurs over a narrower range of nucleotides than with wild-type rho. This suggests that the primary polynucleotide binding site is important not only for efficient termination of transcription but may also be involved in determining the terminal end point of the transcript itself.

Binding Sites↗

Primary aspergillosis affecting the tongue of a leukemic patient.

We describe a case of primary aspergillosis involving the tongue of a patient with acute myeloid leukemia. Intraoral aspergillosis is very rare and we found only 23 cases reported in the English literature. Clinically it was a 2-cm, ulcerated, grayish lesion on the dorsum of the tongue. Microscopically there was invasion of the epithelium, connective tissue and muscle of the tongue by fungal hyphae branching at 45 degrees angle. The large hyphae were easily seen by H & E stain, and were strongly positive for periodic acid-Schiff and Grocott methenamine. The patient was successfully treated with intravenous amphotericin B. Based on clinical, microscopic and culture data, the diagnosis of primary aspergillosis of the tongue was established. Invasive oral aspergillosis is a potentially lethal disease and it should be considered in immunosuppressed patients.

Acute Disease↗

[Permanent hair loss after Kerion Celsi].

Kerion celsi is a deep dermatophytic infection of the scalp. The diagnosis is based on the characteristic clinical picture and is verified by examination for the fungus. Treatment consists of griseofulvin in a dosage of 10 mg/kg/day. The present article is a retrospective investigation of 18 patients with kerion celsi who had been treated in the Department of Dermatology in Marselisborg Hospital during the period 1978-1989. Sixteen out of the 18 patients were children. Twelve of the children were boys. A questionnaire investigation revealed that only five out of 18 patients had normal hair growth. We found a connection between the degree of severity of the alopecia and the age of the patient and the extent of the primary affection, respectively, so that low patient age and large primary affection result in a poorer prognosis. On the other hand, we have not found any connection between the latent period from the first appearance of symptoms and relevant treatment and the alopecia. Nor is there any evidence that treatment with systemic steroid is of significance for the prognosis.

Adult↗

Pastoral relationships and holding work in primary care: affect, subjectivity and chronicity.

OBJECTIVES: To understand family doctors' constructs of long-term therapeutic relationships with patients in primary care. METHODS: Semi-structured interviews were administered to general practitioners with > 5 years of experience (n = 28) working in an English semi-rural district, and the results were subjected to constant comparative qualitative analysis. RESULTS: Participants identified pastoral relationships as long-standing patterns of doctor-patient interaction aimed at providing reliable supportive care indirectly concerned with clinical medicine. Holding work was identified as a technique for structuring and delivering care within pastoral relationships. Pastoral relationships and holding work were seen as valuable in the affective management of people with long-standing chronic illness, especially mild-to-moderate depression and anxiety. DISCUSSION: At a time when primary care is undergoing significant structural change, respondents in this study laid emphasis on personal and continuing relationships with patients who had diffuse needs connected with the experience of complex and chronic problems, and their accounts intimately connected life events with health status. Importantly, these accounts suggest that such relationships are hard to define and therefore hard to measure, but have important therapeutic purposes.

Chronic Disease↗

A prospective follow-up of patients with bipolar and primary unipolar affective disorder.

OBJECTIVE: As part of the National Institute of Mental Health Collaborative Study of the Psychobiology of Depression, the comparative course of manic depressive (bipolar) and primary unipolar patients was assessed. DESIGN: Systematic evaluation using structured instruments every 6 months for a period of 5 years with the recording of remissions, new episodes, and subsequent hospitalizations. PATIENTS: The number of subjects varied somewhat depending on the analyses conducted. For a comparison of course in bipolar patients and unipolar patients, 148 bipolars were compared with 172 unipolar patients. RESULTS: Both unipolar and bipolar patients were more likely to have episodes if they had episodes prior to index admission. Likewise, prior hospitalizations predicted multiple hospitalizations in follow-up. Chronicity was significantly more prevalent among unipolar depressives but in both unipolar and bipolar patients, chronicity diminished over time. Bipolar patients were more likely than unipolar patients to have multiple episodes at the 2-year and 5-year follow-ups. In bipolar patients, there was no difference in the number of episodes in follow-up between males and females but in unipolar patients, females were significantly more likely to have subsequent hospitalizations and episodes than males. Treatment variables did not relate to these differences. A family history of mania or schizoaffective mania predicted multiple episodes in bipolar patients but not in primary unipolar depressives. A family history of all affective illness (mania, schizoaffective mania, bipolar II illness, and depression) did not predict a multiple-episode course in either bipolar or unipolar illness. In unipolar patients, the independent variables leading to multiple-episode course in follow-up are being female, an early age of onset, and prior episodes. CONCLUSIONS: As a result of this systematic follow-up study, new data add to the distinction between bipolar and primary unipolar patients both as regards number of episodes in follow-up and also as regards risk factors that are associated with the multiple-episode course.

Adult↗

Primary factors affecting maximum torsional loading of the tibia in running.

The purpose of this study was to determine primary factors that contribute to the magnitude of the maximum torsional moment on the tibia during running based on information from three-dimensional shank kinematics and ground reaction forces. Eight male subjects were asked to run along a straight track at 5.0 m s-1. Data were collected using two high-speed cameras and a force platform. Each subject's left foot and tibia were modelled as a system of coupled rigid bodies. First, net axial moments acting at both ends of the tibia were calculated using inverse dynamics. Then the tibial torsional moment was determined from the quasi-equilibrium balance of the net tibial axial moments. Our results showed considerable inter-individual variations for the tibial torsional moment during the stance phase of running. The maximum torsional moment reflecting external rotational loading of the proximal tibia was significantly correlated with the outward tilt angle of the shank in the frontal plane (r = 0.78, p < 0.05) and with the vertical force of ground reaction (r = 0.70, p < 0.05). In conclusion, lowering tibial torsional loading by interventions based on the present findings may lead to the reduction of running injuries that occur in athletes' tibiae.

Adult↗

Intrasaccadic target steps during the deceleration of primary saccades affect the latency of corrective saccades.

This study investigates how visually guided saccades and subsequent corrective saccades are affected by a secondary target step occurring at different times during the primary saccade. Eye movements of human subjects were measured by means of a differential infrared light reflection technique while the subjects performed visually guided saccades to a laser spot in darkness. The target was stepped backward or onward during the targeting saccade. While the intrasaccadic target step did not influence gain, peak velocity or skewness of the primary saccade, it had a significant effect on the subsequent corrective saccade when the secondary target step occurred during the deceleration phase of the primary saccade: the latency of the corrective saccade was significantly increased compared with the one performed under the single-step control condition. This increase also occurred when single target steps were presented randomly intermixed with backward and onward double target steps and even between selected sub-samples of saccades with identical postsaccadic visual error. If the target step occurred early during the primary saccade, the latency of the corrective saccade was not changed. This indicates that visual information sampled during the deceleration phase of a saccade can lead to a cancellation of the normal trigger mode of corrective saccades.

Deceleration↗

Pollutional and meteorological factors are closely related to complaints of non-allergic, non-infectious perennial rhinitis patients: a time series model.

BACKGROUND: Epidemiological studies in the past have focused on meteorological conditions, pollution and pollen and their relationship with symptoms of bronchial hyper-reactivity, however, there are no epidemiological studies which examine a wide range of such factors and determine their role in nasal hyper-reactivity. OBJECTIVE: To investigate whether environmental factors can influence symptomatology in non-allergic non-infectious perennial rhinitis (NANIPER) patients, who suffer primarily from nasal hyper-reactivity symptoms. METHODS: We studied 16 non-smoking NANIPER patients and seven non-smoking controls during a 218-day study period (March-October) by means of daily symptom scores and visual analogue scales for the subsets patency, secretions and sneezing, and compared them to seven primary factors which affected 'symptoms' and 10 secondary factors which affected primary factors only. RESULTS: The mean symptom scores in the NANIPER and control groups were 2.17 and 0.13, respectively. In NANIPER, the highest correlations of primary factors with symptomatology were found for symptom scores and sneezing with minimum daytime temperature (r = -0.62 and -0.45, respectively), ozone and NO concentrations. Patency and secretions were associated with minimum daytime temperature (r = -0.39 and 0.32, respectively). Time series analysis, however, correcting for several confounders such as autocorrelated symptomatology, showed that minimum daytime temperature and daytime relative humidity made an independent contribution to symptoms. In the control group, correlations were much lower, though present. Time series analysis was not possible. CONCLUSIONS: We conclude that in a mild climate with relatively low levels of pollution, minor pollution and meteorological disturbances result in substantial changes in nasal reactivity symptoms in NANIPER patients, but not controls, irrespective of other factors such as allergy or infection.

Adolescent↗