Unrelenting Depression and Suicidality in Women with Autistic Traits.

Understanding the cognitive and emotional mechanisms that link autistic traits and risk for suicide is a vital next step for research and clinical practice. This study included a broad sample of adult women (n = 74) who report finding social situations confusing and/or exhausting, and who score high on measures of autistic traits. Regardless of autism diagnostic status, these women reported high rates of suicidal thoughts and behaviors. Depression symptoms were more associated with suicidality than were autistic trait measures of social communication. Measures of neurotypical "imagination" and of repetitive behavior likewise were associated with suicidality risk. Simultaneously feeling sad and feeling stuck or unable to imagine alternate strategies, may uniquely increase suicide risk in autism.

Evidence for sodium-coupled acid-base transport across the basolateral membrane of the reabsorptive duct of the human eccrine sweat gland.

Intracellular pH was measured in isolated nonperfused ducts of human eccrine sweat glands in vitro to investigate basolateral acid-base transport mechanisms. Bath sodium removal led to a bicarbonate-independent, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid insensitive acidification. The recovery of this acidification was ethylisopropyl amiloride sensitive, suggestive of basolateral sodium:hydrogen exchange. Whereas bath chloride removal led to a small acidification this was not 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid sensitive and its causes remain unclear. Elevation of bath potassium to depolarize the basolateral membrane led to a small alkalinization but this was not mimicked by addition of barium or chloride removal. As chloride removal and barium addition would be expected to cause larger depolarizations than potassium elevation these observations do not support a major role for electrogenic acid-base transport. In conclusion, although this study does not support a major role for electrogenic acid-base transport, it has demonstrated the basolateral presence of sodium-coupled acid-base transport in the reabsorptive duct of the human eccrine sweat gland, which most likely represents a sodium:hydrogen exchanger involved in regulation of intracellular pH.

Symptom differences in major depression, dysthymia, panic disorder, and generalized anxiety disorder.

OBJECTIVE: The authors compared symptom features of specific subtypes of depressive and anxiety disorders. METHODS: Psychiatric outpatients with moderate levels of psychopathology and DSM-III diagnoses of major depression, dysthymia, panic disorder, or generalized anxiety disorder were given five standard measures of symptoms of anxiety and depressive disorders. Most of the outpatients were white, and most were middle-class. RESULTS: Principal components analysis revealed 12 orthogonal symptom components. Discriminant function analysis indicated that anxiety was distinguished by specific autonomic arousal symptoms, threat-related cognitions, and subjective anxiety and tension. Discriminant function analysis also indicated that depression was distinguished by anhedonia, cognitions of personal loss and failure, and dysphoric mood. CONCLUSIONS: As nosological categories, major depression and panic disorder were better differentiated by specific symptom markers than dysthymia and generalized anxiety disorder.

Measurement of cutaneous blood flow velocity in delayed hypersensitivity reactions in guinea pigs.

The blood flow velocity in the skin of the flanks of guinea pigs can be measured precisely by laser Doppler velocimetry, provided the animal is mildly sedated. The probe holder can be attached to the shaved skin with cyanoacrylate glue and can be detached after completion of blood flow velocity measurements by application of acetone without harming the animal. The technique is pain-free and non-invasive: it can be used to make serial measurements on the same animal. The system has demonstrated hyperaemia in delayed-type responses to tuberculin PPD, ovalbumin and Keyhole Limpet Haemocyanin with immunological specificity. The time course of evolution and resolution of the vasomotor response accords with previous experience. The method can detect hyperaemia-inducing mediators in the supernatant of antigen or mitogen stimulated lymphocyte cultures and could be used for their bioassay.

Dynamic thermographic imaging for estimation of regional perfusion in the tuberculin reaction in healthy adults.

A sensitive method for measurement of the volume of blood flow through the skin, based on the kinetics of reheating after localised cooling, is described in this paper. This method has been used to study the tuberculin reaction as a model of cutaneous delayed-type hypersensitivity (DHS) in man. Over the positive reaction there is accelerated reheating similar in kinetics and extent to that seen after maximal hyperaemia induced by intradermal injection of histamine or prostaglandin E2. The earlier phase of reheating (10-100 s) is more dependent on blood flow, whereas the later phase (100-300 s) is apparently more dependent on non-perfusion heat exchange mechanisms, including conduction. The reheat kinetic method is largely dependent on blood flow in the deep dermal vessels (diameter > 50 microns), whereas the alternative approach of measurement of the velocity of flow of erythrocytes in the microcirculation by laser Doppler (LD) flowmetry gives results biased towards the most superficial dermal circulation. Previous studies with LD flowmetry have shown that the blood velocity is greatest at the centre of weak and strong reactions, while in the most intense reactions it is raised at the centre but maximal at the periphery (central relative slowing, CRS) raising the possibility of central ischaemia. The reheat kinetics approach has now indicated that the deep dermal circulation is not impaired in CRS reactions. It is concluded that there must be partial obstruction of the parts of the microcirculation communicating between the deep and superficial dermal plexuses, presumably from the accumulation of exudate oedema in the most intense tuberculin reactions.

A simple method for determining the extent of cellular contamination in peripheral blood lymphocyte preparations.

A method is described for calculating, from the size distribution of the cells, the extent of cellular contamination of lymphocyte concentrates prepared from venous blood. The precision of this method was checked by direct comparison with differential leucocyte counts obtained by direct microscopy on 29 samples chosen because they showed a wide range of intensity of contamination. By virtue of its technical simplicity, the method has proved useful in a diagnostic service laboratory for checking the purity of lymphocyte preparations either before performing lymphocyte function tests or after a period of 24 h in tissue culture.

A new method of testing for mitogen-induced lymphocyte stimulation: measurement of the percentage of growing cells and of some aspects of their cell kinetics with an electronic particle counter.

Human lymphocytes were cultured with or without added PHA for periods not exceeding one day so that none of the cells had entered the first mitotic division. The size distribution of the cells was measured with an electronic particle counter and the results were collected in a multichannel analyser. An iterative stochastic model was developed to estimate the proportion of responding cells and their growth characteristics. This mathematical model was based on a few simple assumptions about the pattern of cell growth and was considered to fulfill basic requirements of plausibility and parsimony. The technique described in this paper makes measurement of the absolute percentage of responding cells and their average growth rate in mitogen-induced lymphocyte stimulation tests possible in routine diagnostic laboratories for the first time.

Measurement of phagocyte chemiluminescence in a microtitre plate format.

Previously described assays of phagocyte chemiluminescence have required large numbers of cells and have not been able to follow responses from a large number of samples in single experiments. Recently, sensitive luminometers which employ a 96 well microtitre plate format have become available. We describe the application of this equipment to the measurement of phagocyte chemiluminescence using lucigenin to enhance the response and the estimation of the opsonic activity of serum. It was found that as few as 5 X 10(4) cells (polymorphonuclear leukocytes or monocytes) per well and a ratio of 10:1 zymosan particles to cells gave good results when opsonised with 10% whole serum. This method allows assays of opsonic activity to be performed in triplicate on large numbers of sera with a relatively small number of phagocytes and should aid the investigation of the role of opsonisation in infectious disease.

Measurement of skin swelling in the tuberculin test by ultrasonography.

A new method is described for non-invasive measurement of the thickness of the skin at the site of a skin test from the echo pattern of a pulsed ultrasonic (15 MHz) A-mode scanner. In tuberculin tests on normal volunteers, the skin thickness increased rapidly during days 1 and 2 and was usually greatest at day 4. The echogram measurements can be used to calculate the increase in skin volume and this is disproportionately greater than would be expected from measurements of the diameters of erythema and induration.

A new method for semi-automated quantitation of E-rosettes using a particle size analyser (Coulter Channelyzer).

Visual counts of the number of SRBC attached to individual lymphocytes in E-rosette preparations from 3 healthy young adults were made by 3 experienced observers: from these data the size distribution profile of particles in each E-rosette preparation was calculated. In parallel experiments the size distribution profile was measured directly with a particle size analyser (Coulter Counter and Channelyzer): in every case the observed profile lay within the 95% confidence band around the reconstructed profiles. It was concluded that the Coulter Channelyzer profile is an accurate measurement of the E-rosette size distribution and that particle sizing could provide a reasonable basis for semi-automated tests for E-rosettes. A mathematical model has been developed by which the percentage of lymphocytes forming E-rosettes, the distribution of number of attached SRBC and the average avidity of the lymphocyte receptor for SRBC could be deduced from the size-distribution profiles. The method has a high degree of precision, and a good correlation (P less than 0.01) was obtained when the percentage of E-rosettes (defined for this purpose as having three or more attached SRBC) obtained from the new method was compared with results from standard light microscopy.

The sensitivity of peripheral blood lymphocytes to growth inhibition by hydrocortisone is not determined by their OKT4:OKT8 ratio.

Normal adult human subjects show considerable variation in sensitivity to depression of the activation phase of mitogen-induced lymphocyte growth by the natural glucocorticoid, hydrocortisone. In a study of 21 subjects, the slope of the log-dose response to hydrocortisone was unrelated to the relative numbers of cells in the two major T-cell subpopulations stained by the OKT4 and OKT8 monoclonal antibodies. It is concluded that the extent of the glucocorticoid-induced suppression of early mitogen-stimulated lymphocyte growth is probably not determined by relative numbers of the various immunoregulatory lymphocytes.

Observer variability in reporting of breast lesions.

The consistency of histological diagnosis of breast lesions by members of the panel was studied using a simplified six point classification system that covered the range from normal tissue to invasive carcinoma. In a representative set of 40 sections of the range of breast disease included in the Trial for Early Detection of Breast Carcinoma (the consecutive series), there was, overall, 82% agreement between the diagnoses submitted by members of the panel: diagnosis was virtually consistent (99% agreement) for frankly invasive carcinoma, but there was much greater variability in the diagnosis of borderline lesions. Diagnostic consistency was greatly improved when two categories only (benign and malignant) were considered (94% agreement). The diagnostic consistency of individual pathologists was studied by recirculating the sections: the overall agreement was 78% and, again, most of the inconsistencies occurred when borderline lesions were diagnosed. Additional studies were undertaken on borderline lesions that had been flagged during the first two years of the trial (the borderline series). Unsurprisingly, there was less agreement among the pathologists when all six diagnostic categories were used (70% and 77% for the specimens from the first and second years, respectively), but consistency was greatly improved when classification was simplified to either benign or malignant (86% and 91%, respectively). The diagnoses submitted by individual pathologists were found to deviate from the "majority" diagnosis to a relatively minor extent: each pathologist was generally consistent in either under-diagnosing or overdiagnosing in both the consecutive and borderline series.

Histometry of thyroids containing few and multiple nodules.

Histometric measurements were made on individual nodules and the internodular thyroid on glands from 15 patients without evidence of endocrine thyroid disease: some of the thyroids had multiple nodules. Measurements of the surviving internodular thyroid tissue showed that the various components were each within the normal range for thyroids from patients with no evidence of thyroid disease, but there were considerable deviations within a few glands in the colloid:epithelium ratio that were associated with histological appearances of dilated or collapsed acini. The interpretation of these appearances presented difficulties, but it was concluded that the balance of evidence favoured the inference that the internodular part of the gland was under physiological growth control at the time of study. The nodules varied in size: most contained proportionately less epithelium and more colloid than the internodular thyroid. It was concluded that the nodules were unlikely to be secreting autonomously in these patients.

Does preoperative iodide treatment for thyrotoxicosis bring about involution?

It is generally believed that preoperative iodide decreases the hyperplasia of the toxic thyroid gland. Histometric studies of glands from thyrotoxic patients pretreated with propranolol alone compared with those from patients pretreated with propranolol and iodide failed to confirm this. Although histological appearances and volume percentage measurement of component tissues suggested that the glandular epithelium had involuted after iodine treatment, measurement of their absolute mass indicated that the mean mass of epithelium was the same in both groups and that involution had not occurred. We conclude that considerable confusion in the thyroid literature has arisen through incorrect use of the term involution.

The predictive value of histometry of thyroid tissue in anticipating hypothyroidism after subtoatl thyroidectomy for primary thyrotoxicosis.

Thyroid tissue removed at partial thyroidectomy from primary thyrotoxicosis patients, after preparation for operation with carbimazole and Lugol's iodine, was studied with the histometric technique. In patients with little or no evidence of autoimmunity before operation, the chance of developing postoperative hypothyroidism was approximately 1 in 2 in those who had volume percentage of epithelium greater than 40, but only approximately 1 in 10 in those who had volume percentage of epithelium less than 40. This approach may ultimately prove of predictive value in a substantial proportion of patients for anticipating hypothyroidism after subtotal thyroidectomy for primary thyrotoxicosis.

Indexing and filing of pathological illustrations.

An inexpensive feature card retrieval system has been combined with the Systematised Nomenclature of Pathology (SNOP) to provide simple but efficient means of indexing and filing 2 in. x 2 in. transparencies within a department of pathology. Using this system 2400 transparencies and the associated index cards can be conveniently stored in one drawer of a standard filing cabinet.

Cell death in granulomata: the role of apoptosis.

Unequivocal apoptosis were seen by light microscopy in examples of leprosy, sarcoidosis, tuberculosis, Crohn's disease and foreign body granulomata. A limited electron microscopic investigation showed typical apoptotic bodies in both sarcoid and leprosy granulomata. The number of apoptosis and mitoses in granulomata were counted and their densities calculated. The wide variation in the results between individual lesions may reflect differences in disease activity.

Grading of astrocytomas using a Quantimet 720 image-analysing computer.

Cerebral astrocytomas and undifferentiated gliomas were graded by (1) Kernohan classification on the basis of visual microscopy, and (2) optical density/area profiles obtained by automated densitometry with a Quantimet 720 image-analysing computer. In a retrospective study of 44 patients the Quantimet measurements seemed to give a more accurate assessment of prognosis than visual grading.

Differential cell counts in the histiocytic variant of lymphocytic predominance subtype of Hodgkin's disease.

Differential cell counts were made on a lymph node, the structure of which was replaced by the histiocytic variant of the lymphocytic predominance subtype of diffuse Hodgkin's disease. In terms of numbers of cells in various categories, this lymph node bears a closer relationship to the mixed cellularity subtype than to the classical lymphocytic predominance subtype. In this node, unlike the mixed cellularity subtype, the histiocytes are largely differentiated into epithelioid cells; the significance of this cellular adaptation for defence against neoplastic cells is not known.

Unresponsiveness to skin testing with bacterial antigens in patients with haemophilia A not apparently infected with human immunodeficiency virus (HIV).

Unresponsiveness to skin testing with PPD and tetanus toxoid was commonly seen in patients with haemophilia A but not infected with human immunodeficiency virus but was uncommon in controls. Vaccination history indicated that the unresponsive patients had not been immunised in childhood. Other tests of immune competence (skin tests with other antigens, lymphocyte stimulation with mitogens and antigens, and viral serology) showed that the haemophilia A patients had an adequate response to pathogens to which they had been exposed. Five of 12 such patients had a mild T4 lymphopenia, and this may have been related to parenteral administration of large quantities of protein.