A new era for giant cell arteritis.

The landscape of the investigation and management of giant cell arteritis (GCA) is advancing. In this review we will outline the recent advances by searching the current English literature for relevant articles using key words of giant cell arteritis, temporal arteritis, Horton's disease, investigation, and treatment. Delay in diagnosis, diagnostic uncertainty and glucocorticoid (GC) morbidity are among the highest concerns of clinicians and patients in this disease area. The positive news is that fast track pathways, imaging techniques and new therapies are emerging for routine management of GCA. Future directions for intervention in the treatment paradigm will be discussed.

Further observations on tuberculin reactions in active tuberculosis.

One hundred patients with active tuberculosis were tested for tuberculin reactivity within 24 hours of their admission to the hospital. Commercial intermediate tuberculin, Tween stabilized intermediate tuberculin and the Tine test as well as a mumps antigen were applied simultaneously. False negative reactions were obtained in 28 per cent with Tine testing and in 21 per cent with Tween stabilized as well as plain tuberculin. These nonreactors were clinically identifiable as seriously ill with manifestations primarily attributable to protein depletion as a result of their illness. This is not specifically related to the effects of tuberculosis itself, but can be demonstrated in patients suffering the same sequelae of other debilitating illness. After two weeks of protein supplementation via a high calorie, high protein, hospital diet, skin reactivity was restored in the vast majority of these nonreactors. It is concluded that the lack of tuberculin reactivity on hospital admission probably results from impaired lymphocyte function in patients suffering serious protein depletion as a result of their illness; it is not attributable to deficiencies in the tuberculin test itself.

Nongranulomatous interstitial pneumonitis in sarcoidosis. Relationship to development of epithelioid granulomas.

Nongranulomatous, nonspecific interstitial pneumonitis was a predominating or prominent histopathologic finding in 62 percent of 128 granuloma-containing specimens from open lung biopsies obtained from patients with sarcoidosis. Data from this study, combined with observations by others on the evolution of experimentally induced granulomas, indicate that interstitial pneumonitis represents a very early lesion, possibly the initial lesion, in pulmonary sarcoidosis. Because of the relatively large error of sampling inherent in the currently increasing practice of obtaining small specimens for lung biopsy via the flexible fiberoptic bronchoscope, we anticipate that interstitial pneumonitis will be seen as the only histopathologic finding in these specimens with increasing frequency. It is therefore important to recognize that interstitial pneumonitis is a characteristic, although nondiagnostic, morphologic feature of pulmonary sarcoidosis.

Pulmonary tuberculosis and bronchocentric granulomatosis.

Bronchocentric granulomatosis (BG) is an uncommon inflammatory lesion of unknown etiology defined on morphologic grounds by the presence of necrotizing granulomata centered on bronchi and bronchioles. We report the typical pathologic features of BG in a patient with tuberculosis. Mycobacterial and other types of infection should be excluded by appropriate stains and cultures in all patients with BG on lung biopsy, especially those who are nonasthmatic.

Adult respiratory distress syndrome as a cause of death in pneumococcal pneumonia. Report of ten cases.

The Pneumococcus continues to be a common cause of infectious pneumonia; however, the cause of death in pneumococcal disease remains obscure. Ten patients are described who developed the adult respiratory distress syndrome (ARDS) secondary to pneumococcal pneumonia. The patients are young (median age, 33 years) and leukopenic (median white blood cell count, 2.1 cells/cu mm) and have a mortality of 50 percent (five patients). It is postulated that pulmonary sequestration of leukocytes may play a role in the pathogenesis of ARDS secondary to pneumococcal disease. Four different pneumococcal capsular subtypes (9V [68]; 9A [33]; 4; 3) were found capable of causing ARDS. The currently available pneumococcal vaccine does not contain two of the capsular subtypes associated with ARDS.

A comparative study of subcutaneously administered terbutaline and epinephrine in the treatment of acute bronchial asthma.

Terbutaline, a new bronchodilator drug reported to have selective affinity for beta 2-adrenergic receptors, was compared with epinephrine in the treatment of 49 adult subjects with acute bronchial asthma. Under double-blind conditions, 24 subjects received 1.0 mg of terbutaline sulfate, and 25 subjects received 0.5 mg of epinephrine hydrochloride subcutaneously. Spirometric measurements, heart rate, and blood pressure, as well as subjective responses, were recorded prior to, and then at 5, 15, 30, 60, and 120 minutes after administration of the drug. The results indicate that terbutaline is an effective bronchodilator drug in subjects with acute asthma; however, the heart rate rose significantly after administration of terbutaline, with a maximal increase of 25 percent above control. Review of the literature reveals that tachycardia is a consistent finding when subcutaneous doses of terbutaline in excess of 0.25 mg are administered. Stimulation of beta 1-adrenergic receptors in the heart appears to be the most important factor involved in this response. A lesser cardioaccelerator effect was observed after administering epinephrine in a dose producing an equivalent degree of bronchodilatation.

Acute pulmonary complications in systemic lupus erythematosus. Immunofluorescence and light microscopic study.

Lung tissue obtained from eight consecutive patients with systemic lupus erythematosus complicated by severe, acute pulmonary disease was studied by both light and immunofluorescence microscopy. Light microscopic examination disclosed interstitial pneumonia in four cases, cytomegalovirus pneumonitis in one case, bronchiolitis and peribronchiolitis in one case, pulmonary infarction in one case and focal atelectasis in the remaining case. Direct immunofluorescence examination revealed focally bound immunoglobulins or complement (C3) within pleural and/or pneumocyte nuclei in each specimen. Immunohistologic studies in these cases may thus suggest a diagnosis of systemic lupus erythematosus with acute pulmonary complications, despite the lack of specificity of the pathologic changes seen by light microscopy.

Elevation of angiotensin-converting enzyme in granulomatous lymph nodes and serum in sarcoidosis: clinical and possible pathogenic significance.

A statistically highly significant elevation of serum ACE was found in a group of 58 patients with sarcoidosis (serum ACE was elevated in 34% of patients), as compared with normal controls and patients with tuberculosis and various other common diseases. The results suggest that serum ACE is a useful aid for the diagnosis of sarcoidosis when elevated, but that a normal value does not rule out the condition and may occur in more than one-half of monitored patients. There is a trend to diminution of serum ACE with increasing duration of disease with or without steroid therapy, perhaps correlating with the total body mass of active granulomas, as indirectly suggested in preliminary data by correlation of serum ACE with serum globulin in 16 sarcoidosis patients. It is not yet clear whether there is any significant steroid effect on serum ACE, but a significant number of patients on steroid therapy for more than 2-4 yr have elevated serum ACE values, which in some instances are extremely high. There was a 12-fold elevation in ACE to specific activities generally exceeding those of normal lung in granulomatous lymph nodes of 14 patients with sarcoidosis, suggesting that sarcoid granulomas may be actively synthesizing ACE and resulting in elevation of serum ACE. Extensively fibrotic sarcoid lymph nodes had normal or slightly elevated ACE, suggesting that obliteration of granulomas in sarcoid lymph nodes diminishes their ACE content and that this obliteration may be related to the tendency to diminution of serum ACE with time. ACE was not elevated in one tuberculous lymph node or in experimental granulomas, suggesting that elevation of ACE may have some specificity for the granuloma of sarcoidosis rather than being a characteristic of all granulomas. The catalytic and physical properties of ACE in serum and lymph nodes in sarcoidosis were generally similar to normal ACE with respect to pH activity, modulators, polyacrylamide-gel electrophoresis, and Sephadex G-200 gel filtration. However, sarcoid lymph node ACE appeared to be more heat labile than normal lung or lymph node ACE, suggesting the possibility that an abnormal ACE may be present in sarcoidosis. If an abnormal enzyme is indeed present, it might be coded for by a host gene that is not normally expressed or a nonhost gene or it might be a normal ACE that has been altered. No ACE activity was found in circulating white blood cells in sarcoidosis or in control subjects, suggesting that circulating white blood cells may not contain the epithelioid cell precursor or that ACE synthesis (or less likely, uptake) may be turned on at a later stage in the transformation. Lysozyme activity was also elevated in sarcoid lymph nodes. Serum ACE and serum lysozyme were significantly positively correlated in 16 sarcoidosis patients, suggesting a relationship between the two...

Mechanisms involved in the immunotoxicity induced by dermal application of JP-8 jet fuel.

Dermal application of JP-8 jet fuel induces immune suppression. Classic delayed-type hypersensitivity as well as the induction of contact hypersensitivity to allergens applied to the shaved skin of JP-8-treated mice is suppressed. In addition, the ability of T cells isolated from JP-8-treated mice to proliferate in vitro is suppressed. Here we focused on further characterizing the immunotoxicity induced by JP-8 exposure and determining the mechanism involved. Suppression of T-cell proliferation was first noted 3 to 4 days after a single JP-8 treatment and lasted for approximately 3 weeks, at which time T-cell proliferation returned to normal. Cellular immune reactions appear to be more susceptible to the immunosuppressive effects of JP-8, as antibody production in JP-8-treated mice was identical to that found in normal controls. The mechanism through which dermal application of JP-8 suppresses cell-mediated immune reactions appears to be via the release of immune biological-response modifiers. Blocking the production of prostaglandin E(2) with a selective cyclooxygenase-2 inhibitor abrogated JP-8-induced immune suppression. Neutralizing the activity of interleukin-10 with a highly specific monoclonal antibody also blocked JP-8-induced immune suppression. Furthermore, injecting JP-8-treated mice with recombinant interleukin-12, a cytokine that drives cell-mediated immune reactions in vivo, overcame the immunotoxic effects of JP-8 and restored immune function. These data indicate that immune suppressive cytokines, presumably produced by JP-8-treated epidermal cells, are responsible for immune suppression in JP-8-treated mice and that blocking and/or neutralizing their production in vivo overcomes the immunotoxic effects of JP-8.

A microprocessor-based tissue displacement monitor for in vitro quantification of knee capsule deformation.

The advantages of utilizing a microprocessor design kit as a central element in custom laboratory instrumentation are demonstrated in the design of a real-time, multiple point, tissue displacement monitor. The tissue sample to be monitored is submerged in a saline bath, through which perpendicular electric fields are alternately generated. Analog displacement data are generated by differentially amplifying the voltage between each of 4 sense electrodes attached to the tissue surface, and a reference electrode, positioned on the tissue surface central to the sense electrodes. The microprocessor unit is used to control field generation, to multiplex the sensing electrode signals through the analog signal processing electronics, and after analog-to-digital conversion, to scale and interface the digital displacement data to a host processor.

Task-dependent properties of brain stimulation reward.

Lawful relationships established between lever-pressing and parameters of brian stimulation reward (BSR) were examined for several tasks. Task-contingent BSR was given to the same rats at identical sites using identical stimulation parameters. Lengthening stimulation duration from 100 to 300 msec increased lever-press rates. Subsequent lengthening from 400 to 800 msec decreased lever-press rates. Wheel-turning rates increased linearly with lengthening duration. The form of the response-duration function depended on current for lever-pressing but not for wheel-turning. As duration lengthened, time between responses increased systematically for the lever and was invariant for the wheel. Stimulation of the substantia nigra, posterior medial forebrain bundle, and anterior hypothalamus produced similar relations. To further examine the generality of these findings, licking and barrier-jumping were tested. Licking decreased monotonically as stimulation duration lengthened. Barrier-jumping increased from 100 to 500 msec and subsequently remained stable despite lengthening duration to 900 msec. In all tasks examined BSR was rewarding, but the form of the response-duration function depended on task characteristics. Since identical sites were stimulated, task differences cannot be attributed to neurochemical substrates. Results provide evidence for behavioral constraints on BSR.

Stimulation of collagenase secretion from rheumatoid synovial tissue by human collagen peptides.

Dayer et al. demonstrated that mononuclear cells from human peripheral blood produce a mononuclear-cell factor that stimulates collagenase secretion from adherent rheumatoid synovial cells. The production of this mononuclear-cell factor can be stimulated by phytohemagglutinin, a T-cell mitogen. We have examined immune mechanisms by which collagenase secretion may be stimulated from explants of rheumatoid synovial tissue and from primary monolayer cultures of rheumatoid synovial cells. Conditioned media from cultures of normal peripheral-blood mononuclear cells that had been activated by phytohemagglutinin stimulated collagenase secretion from most explants and from all monolayer cultures that were examined. The direct addition of phytohemagglutinin stimulated collagenase secretion in explants from eight of fourteen patients and in monolayer cultures from three of six patients. These observations indicate the presence of responsive T lymphocytes in rheumatoid synovial tissue and implicate them in the stimulation of collagenase secretion from synovial cells. The direct addition of type-II collagen peptides to rheumatoid explants also stimulated collagenase secretion in explants from six to fifteen patients. Four of five of these patients displayed moderate or severe disease activity. Other patients showed a marginal stimulation of collagenase secretion on addition of type-II collagen peptides (four of fifteen patients) and type-I collagen peptides (three of twelve patients). None of the patients with mild or inactive disease responded to type-II collagen. With one exception, the addition of collagen peptides to monolayer cultures did not stimulate collagenase secretion. An increased production of factors that enhance or inhibit the migration of polymorphonuclear leukocytes was also observed in explant cultures in response to the addition of phytohemagglutinin (in seven of twelve patients), of type-I collagen peptides (in five of ten patients), and of type-II collagen peptides (in five of eleven patients). There was no correlation between production of these factors and stimulation of collagenase secretion in rheumatoid synovial tissue.

Granulomatous pulmonary angiitis in sarcoidosis.

The occurrence and morphologic aspects of granulomatous pulmonary angiitis were evaluated in open lung biopsy specimens from 128 patients with sarcoidosis. All of the specimens showed parenchymal granulomas characteristic of sarcoidosis, and in 88(69%), granulomatous angiitis was seen. In the speclimens that exhibited granulomatous angiitis, venous involvement was mos common, seen in 92% of the cases. In 61% of these biopsy specimens, only venous involvement was seen; in 31%, both venous and arterial involvement was present. Only 8% of the positive specimens showed arterial lesions exclusively. The extent of angiitis was quantitated. Focal segmental elastic tissue destruction, partial or complete, was a common finding. No instances of aneurysm formation, endothelial erosion, or thrombosis were observed. Occlusive narrowing of small vessels was frequent. Bronchial blood vessels were not involved.

Seminal vesicle growth induced by Ascaris suum infection.

This study was designed to determine the effect of Ascaris suum infection upon growth of mouse vesicular glands. Mice were infected with varying dosages of A. suum eggs and killed after six weeks. Results indicated a dose dependent increase in seminal vesicle weight, independent of total body weight.

Seminal vesicle and coagulating gland growth induced by intraperitoneal inoculation of fungi in mice.

The effect of fungi on the growth of body organs in mice was investigated. Single, intraperitoneal injections of yeasts (Cryptococcus albidus, Saccharomyces cerevisiae, Schizosaccharomyces octosporus) or molds (Aspergillus niger, Geotrichum candidum, Mucor haemalis) induced an increase in the mass of seminal vesicles and coagulating glands independent of whole body weight changes in mice.

Indications for the use of tranylcypromine and trifluoperazine (Parstelin).

Thirty-two patients were treated with the combination of tranylcypromine and trifluoperazine (Parstelin). The patients fell into 3 clinical groups, namely, endogenous depression (7 patients), neurotic depressive reaction (10 patients) and phobic anxiety with some depressive features (15 patients). Satisfactory response was found in 10 out of the 15 patients with phobic symptoms. The response in the other 2 groups was not significant. Side effects were troublesome in the neurotic depressive reaction group. In the phobic group the symptoms of the patients who responded were inclined to recur when the treatment was discontinued. It is considered that it is a useful preparation in the treatment of some phobic patients, but one must expect that the patients are likely to have to remain on the drug for long periods of time.

Psychological screening for vasectomy.

PIP: 286 men presenting for vasectomy were interviewed preoperatively as a psychological screening; their wives were interviewed separately. Age range was from 23-49 years. Number of children tended to be small (mean, 2.7 children/couple). The length of time the couple was married varied widely (5-25 years). In this screening interview special reference was made to emotional and sexual difficulties in the marriage. Contraceptive history and sexual practice were also elicited. Serious chronic physical illness was reported in 10% of wives and 19% had histories of obstetrical and gynecological problems. Reasons for deciding on vasectomy were varied, but generally revolved around the absolute effectiveness of the procedure and the need to unburden the wife of contraceptive responsibility. Vasectomy was refused in 26 men and in another 11 cases the procedure is being deferred; the main contraindications were sexual difficulties and in stability within the marriage (vasectomy reversal requests often follow divorce).^ieng