Ultrastructural and three-dimensional analysis of the contractile cells of the cutaneous microvasculature.

The three-dimensional relationships between smooth muscle cells and endothelial cells and between pericytes and endothelial cells in four segments of the microcirculation were analyzed by computer reconstructions from serial electron micrographs. In elastic-containing arterioles, the smooth muscle cells formed an inner longitudinal layer above and parallel to the elastica and an outer spiral layer. In the terminal arterioles the two layers of smooth muscle cells and elastica were replaced by a single smooth muscle cell that completely encircled the endothelial cell tube. The pericytes in the post-capillary venules completely encircled and gripped the endothelium through multiple contact points from their lateral processes. In the large venules the pericytes only partially encircled the endothelial cell tube and were more randomly placed.

The response of psoriatic epidermis and microvessels to treatment with topical steroids and oral methotrexate.

In a previous paper we showed that the microvessels in a psoriatic plaque as studied by electron microscopy returned to normal before the labeling index of the basal cells did during successful therapy with PUVA or the Goeckerman treatment. In this paper we studied the same parameters in 4 additional psoriatic patients: 2 received oral methotrexate and 2 were treated with a topical steroid under plastic wrap occlusion. The labeling index of the basal cells returned to normal in 3 and near normal in 1. The histologic features of the psoriatic epidermis became normal except for mild to moderate acanthosis, but the capillary loops in the dermal papillae retained their venous capillary ultrastructure and showed no signs of reversion to a normal arterial capillary configuration. The lack of response of the dermal capillaries to the topical steroid and oral methotrexate during the initial clinical improvement raises the possibility that the clinical relapses in psoriasis which may promptly follow discontinuation of topical steroid therapy and oral methotrexate may be related to an inability of these drugs to restore the microvasculature to normal in such situations.

Role of the microcirculation in the treatment and pathogenesis of psoriasis.

Controversy exists whether the initiating events in psoriasis are primarily epidermal or dermal (vascular). To study this point, serial biopsies from 6 patients were taken from the periphery of individual plaques before, and at 1 to 3 day intervals during, Goeckerman and PUVA treatments. Part of the biopsy was studied by electron microscopy to determine the fine structure of the capillary loops and part was incubated with tritiated thymidine to determine the labeling index (LI) of the basal cells. Normal appearing buttock skin of the 11 other psoriatic patients not under treatment was studied by identical methods. In 4 of the 6 treated patients, the capillary loops began to return toward normal 3 to 8 days before the LI began to decrease. Two patients did not show a return toward normal of either capillaries or LI during the period of the experiment. The LI was elevated in the normal appearing buttock skin of 6 of 11 untreated psoriatics. In 4 of the 6, the loops were normal arterial capillaries. We did not observe abnormal (venous) capillaries associated with a normal LI in the other 5 untreated patients. These data support the concept that the initiating factors in psoriasis are in the epidermis, but epidermal hyperplasia cannot occur without vascular proliferation. Understanding the factors responsible for shortening the capillary loops during epidermal normalization and for inhibition of capillary growth in the presence of an increased LI could lead to other ways of controlling psoriasis.

A study of the veil cells around normal, diabetic, and aged cutaneous microvessels.

The veil cells around normal, diabetic, and aged vessels were reconstructed in 3 dimensions by a computer graphics system from 120-140 serial ultrathin sections. The normal vessel was surrounded by a single layer of veil cells which had a wrinkled and pleated surface. The diabetic vessels were surrounded by 3-6 layers of cellular material produced by increased numbers of veil cells and their associated cytoplasmic sheets. The veil cells around aged vessels appeared to have the same length as young and diabetic veil cells but were underdeveloped in their lateral extensions so that they did not cover the vessel circumferentially as well as did the normal veil cells. Preliminary data suggest that young, diabetic, and aged veil cells have the same metabolic activity per unit area of cytoplasm and are of the same length. The abnormal thickness or thinness of the vascular wall of dermal microvessels appears to be related to the degree of development and numbers of veil cells around the vessels rather than any change in their basic metabolic activity from normal.

Ultrastructural analysis of the endothelial-pericyte relationship in diabetic cutaneous vessels.

The microvessels in the buttock skin of 15 patients with long-standing juvenile diabetes were studied both by electron microscopy and three-dimensional (3D) computer reconstruction of a prototypical diabetic postcapillary venule. Endothelial cell gaps were found in postcapillary venules and capillaries, but only in association with an increased deposition of basement membrane-like material in the vascular wall. In parallel with the increased amounts of deposited basement membrane-like material, the space between pericytes and endothelial cells was wider and the cytoplasmic processes that formed the contact points between them were longer and thinner than normal. Pericytes, devoid of any cytoplasmic contacts with the underlying endothelial cells, were observed as isolated cells within the outer third of the vascular wall in markedly thickened vessels. These observations offer an explanation for the known increased vascular permeability of diabetic vessels, and suggest a possible explanation for the development of diabetic retinopathy with aneurysm formation.

Increased synthesis of poly(ADP-ribose) in isolated liver nuclei from autoimmune NZB/NZW mice.

The synthesis and degradation of poly(ADP-ribose) were investigated in isolated liver nuclei from autoimmune NZB/W mice and four strains of normal mice. Compared to normal mice the maximum levels of incorporation of [3H]NAD into poly(ADP-ribose) were increased about 2-fold in the autoimmune mice. The kinetics of incorporation suggested that this change was due to an increase in the activity of the polymerase rather than a decrease in the level of degradative enzymes. Thus there may be a connection between autoimmunity and poly(ADP-ribose) metabolism.

Management of corticosteroid-induced osteoporosis.

OBJECTIVES: To educate scientists and health care providers about the effects of corticosteroids on bone, and advise clinicians of the appropriate treatments for patients receiving corticosteroids. METHODS: This review summarizes the pathophysiology of corticosteroid-induced osteoporosis, describes the assessment methods used to evaluate this condition, examines the results of clinical trials of drugs, and explores a practical approach to the management of corticosteroid-induced osteoporosis based on data collected from published articles. RESULTS: Despite our lack of understanding about the biological mechanisms leading to corticosteroid-induced bone loss, effective therapy has been developed. Bisphosphonate therapy is beneficial in both the prevention and treatment of corticosteroid-induced osteoporosis. The data for the bisphosphonates are more compelling than for any other agent. For patients who have been treated but continue to lose bone, hormone replacement therapy, calcitonin, fluoride, or anabolic hormones should be considered. Calcium should be used only as an adjunctive therapy in the treatment or prevention of corticosteroid-induced bone loss and should be administered in combination with other agents. CONCLUSIONS: Bisphosphonates have shown significant treatment benefit and are the agents of choice for both the treatment and prevention of corticosteroid-induced osteoporosis.

Laboratory tests.

Despite impressive advances in our understanding of the natural history of the rheumatic diseases and their treatments, there remains much to be learned. The management of most of these diseases is far from satisfactory for either the clinician or patient. There is little distinction between clinical practice and clinical research. How much and what type of data one should collect clearly depends on the setting and on the clinical/research questions being asked. One must ensure that the literature is relevant to his or her practice. The corollary is that research must be derived from a variety of settings, including both the traditional researcher and the traditional clinician.

Cardiac abnormalities in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of cardiac abnormalities in patients with systemic lupus erythematosus. DESIGN: Prospective survey. SETTING: Rheumatic diseases unit of a university hospital. PATIENTS: Volunteer sample comprising 83% of patients with systemic lupus erythematosus followed annually in the rheumatic disease unit (93 patients; mean age 46 +/- 13 years; female 79, male 14). These patients were age-matched with 16 female control volunteers (mean age 43 +/- 5 years) recruited from hospital staff. INTERVENTIONS: Electrocardiograms, two-dimensional echocardiograms and radionuclide angiograms were performed in patients and controls. Anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay in the systemic lupus erythematosus patients. MAIN RESULTS: At least one cardiac abnormality was detected in 44 of 93 systemic lupus erythematosus patients (47%). These abnormalities included: aortic valve thickening 12%; mitral valve thickening, prolapse, vegetations or stenosis 23%; left ventricular segmental dysfunction 4%; left ventricular global hypokinesis 4%; right ventricular hypokinesis 4%; left ventricular hypertrophy 14%; left ventricular diastolic dysfunction 16%; and pericardial effusion 2%. Three of the 16 controls (19%) had cardiac abnormalities consisting of mitral valve prolapse (one), right ventricular hypokinesis (one) and pericardial effusion (one). Cardiac abnormalities were more common in the systemic lupus erythematosus group compared with controls (47% versus 19%, P less than 0.05). Raised anticardiolipin antibodies were specific (88%) but not sensitive (33%) for the presence of cardiac abnormalities in systemic lupus erythematosus patients. Renal disease and prednisone therapy were more common in systemic lupus erythematosus patients with cardiac involvement than in such patients without evidence of cardiac disease (40% versus 16%, P = 0.03; and 81% versus 59%, P = 0.04, respectively). CONCLUSIONS: Cardiac abnormalities can be identified noninvasively in 47% of patients with systemic lupus erythematosus.

A case of peripartum eosinophilic myocarditis.

A 19-year-old postpartum patient with a previous history of asthma and eosinophilic myocarditis is described. Eosinophilic myocarditis is thought to be caused by exacerbation of the idiopathic hypereosinophilic syndrome by pregnancy. The diagnosis was made by a right ventricular endomyocardial biopsy, which showed an eosinophilic infiltrate with a few scattered foci of myonecrosis, but no fibrosis, vasculitis or granulomas. The patient's myocardial function continued to decline over a two-year follow-up period, despite normal levels of eosinophils. She developed echocardiographic evidence of diastolic and systolic dysfunction.

Apophysial joint degeneration, disc degeneration, and sagittal curve of the cervical spine. Can they be measured reliably on radiographs?

STUDY DESIGN: Interexaminer reliability study. OBJECTIVES: To determine the reliability of grading apophysial joint and disc degenerative changes and the reliability of measuring sagittal curves on lateral cervical spine radiographs. SUMMARY OF BACKGROUND DATA: Several authors have proposed that the presented of degenerative changes and the absence of lordosis in the cervical spine are indicators of poor recovery from neck injuries caused by motor vehicle collisions. The validity of those conclusions is questionable because the reliability of the methods used in their studies to measure the presence of degenerative changes and the absence of lordosis has not been determined. METHODS: Kellgren's classification system for apophysial joint and disc degeneration, as well as the pattern and magnitude of the sagittal curve on 30 lateral cervical spine radiographs were assessed independently by three examiners. RESULTS: Moderate reliability was demonstrated for classifying apophysial joint degeneration with an intraclass correlation coefficient of 0.45 (95% confidence interval, 0.09-0.71). Classifying degenerative disc disease had substantial reliability, with an intraclass correlation coefficient of 0.71 (95% confidence interval, 0.23-0.88). Measuring the magnitude of the sagittal curve from C2 to C7 had excellent interexaminer agreement, with an intraclass correlation coefficient of 0.96 (95% confidence interval, 0.88-0.98) and an interexaminer error of 8.3 degrees. CONCLUSIONS: The classification system for degenerative disc disease proposed by Kellgren et al and the method of measurement of sagittal curves from C2 to C7 demonstrated an acceptable level of reliability and can be used in outcomes research.

Formation of O-6-acetylmorphine in the 'homebake' preparation of heroin.

When O-6-acetylmorphine is found in toxicological or in illicit drugs cases it is usually assumed to be the product of heroin degradation. It is, therefore, used as evidence for the prior existence of heroin. In this study, it was found that, when morphine is partly acetylated with acetyl chloride, O-6-acetylmorphine is produced. In some experiments, partial acetylation of morphine sulphate yielded mixtures which contained O-6-acetylmorphine, unreacted morphine and only traces of O-3-acetylmorphine and heroin. Therefore, in cases where O-6-acetylmorphine is found in the absence of heroin, it should not be used as evidence of heroin having been present.

Editor's Mail.

The Editor welcomes readers' comments, and selected letters are published each month. Letters must be signed and should be sent to Editor's Mail at the address shown. The journal reserves the right to condense letters if necessary for space.

1965-1990: 25th anniversary of nurse practitioners. A classic manuscript reprinted in celebration of 25 years of progress. The Burlington randomized trial of the nurse practitioner. 1971-2.

From July 1971, to July 1972, in a large suburban Ontario practice of two family physicians, a randomized controlled trial was conducted to assess the effects of substituting nurse practitioners for physicians in primary-care practice. Before and after the trial, the health status of patients who received conventional care from family physicians was compared with the status of those who received care mainly from nurse practitioners. Both groups of patients had a similar mortality experience, and no differences were found in in physical functional capacity, social function or emotional function. The quality of care rendered to the two groups seemed similar, as assessed by a quantitative "indicator-condition" approach. Satisfaction was high among both patients and professional personnel. Although cost effective from society's point of view, the new method of primary care was not financially profitable to doctors because of current restrictions on reimbursement for the nurse-practitioner services.