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1.  Triennial Reproduction Symposium: The ovarian follicular reserve in cattle: What regulates its formation and size?1,2 
Journal of animal science  2013;91(7):3041-3050.
The ovarian follicular reserve has been linked to fertility in cattle. Young adult cattle with low vs. high numbers of antral follicles ≥ 3 mm in diameter in follicular waves also have fewer preantral follicles and decreased fertility. This underscores the importance of understanding the factors that regulate early follicular development and establish the ovarian follicular reserve, but little is known about how the follicular reserve is first established. In ruminants and humans, follicles form during fetal life, but there is a gap (about 50 d in cattle) between the appearance of the first primordial follicles and the first growing, primary follicles. In this review we present evidence that in cattle, fetal ovarian steroids (i.e., estradiol and progesterone) are negative regulators of both follicle formation and of the acquisition by newly formed follicles of the capacity to activate (i.e., initiate growth). The results indicate that capacity to activate is linked to the completion of meiotic prophase I by the oocyte. The inhibitory effects of estradiol on follicle activation were found to be reversible and correlated with inhibition of the progression of meiotic prophase I. Fetal bovine ovaries produce steroid hormones and production varies considerably during gestation and in a pattern consistent with the hypothesis that they inhibit follicle formation and capacity of newly formed follicles to activate in vivo. However, little was known about how steroid production is regulated. In our studies, both LH and FSH stimulated progesterone and estradiol production by ovarian pieces in vitro. The addition of testosterone to the culture medium enhanced estradiol production, especially when FSH was also present, but inhibited progesterone production, even in the presence of gonadotropins. Evidence is also presented for effects of maternal nutrition and health and for potential effects of estrogenic endocrine-disrupting chemicals on the size of the ovarian follicular reserve established during fetal life. In summary, fetal ovarian steroids may be important regulators of the early stages of follicular development in cattle. Therefore, external factors that alter steroid production or action may affect the size of the ovarian follicular reserve.
PMCID: PMC5418586  PMID: 23736047
cattle; endocrine-disrupting chemicals; maternal nutrition; ovarian follicle; ovarian follicular reserve; ovary
2.  Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate☆ 
Microvascular Research  2017;111:32-36.
In patients with systemic sclerosis (SSc), fingertip digital ulcers (DUs) are believed to be ischaemic, and extensor surface DUs a result of mechanical factors/microtrauma. Our aim was to assess blood flow response to topical glyceryl trinitrate (GTN) compared to placebo in SSc DUs, looking for differences in pathophysiology between fingertip and extensor lesions.
This was a double-blind, randomised, crossover, placebo-controlled study. Sixteen (6 fingertip, 10 extensor) DUs were each studied twice (one day apart): once with GTN and once with placebo ointment. Perfusion at the DU centre (‘DUCore’) and periphery (‘DUPeriphery’), as measured by laser Doppler imaging was performed before and immediately after ointment application, then every 10 min, up to 90 min post-application. We calculated the area under the response curve (AUC) and the ratio of peak perfusion to baseline, then compared these between GTN and placebo.
Perfusion was lower in the DUCore compared to the DUPeriphery (ratio of 0.52). The microvessels of the DUCore were responsive to GTN, with an increase in perfusion, with a similar effect in both fingertip and extensor DUs. The AUC and peak/baseline perfusion difference in means (ratio, 95% confidence interval) between GTN and placebo at the DUCore were 1.2 (1.0–1.6) and 1.2 (1.0–1.5) respectively, and at the DUPeriphery were 1.1 (0.8–1.6) and 1.0 (0.9–1.2) respectively.
DUs (both fingertip and extensor) were responsive to topical GTN, with an increase in perfusion to the ischaemic DU centre. If both fingertip and extensor DUs have a (potentially reversible) ischaemic aetiology, this has important treatment implications.
•SSc fingertip DUs are believed to be ischaemic, whereas, extensor surface DUs are a result of mechanical factors/microtrauma.•DUs (both fingertip and extensor) were responsive to topical GTN, in particular the ischaemic centre.•If both fingertip and extensor DUs have a ischaemic aetiology, this has important treatment implications.
PMCID: PMC5351498  PMID: 28027937
Systemic sclerosis; Scleroderma; Digital ulcers; Digital ischaemia; Glyceryl trinitrate; Microvascular
3.  Running Backwards: Consequences of Current HIV Incidence Rates for the Next Generation of Black MSM in the United States 
AIDS and behavior  2016;20(1):7-16.
Black men who have sex with men (MSM) in the United States are disproportionately impacted by HIV. To better understand this public health problem, we reviewed the literature to calculate an estimate of HIV incidence among Black MSM. We used this rate to model HIV prevalence over time within a simulated cohort, which we subsequently compared to prevalence from community-based samples. We searched all databases accessible through PubMed, and Conference on Retroviruses and Opportunistic Infections abstracts for HIV incidence estimates among Black MSM. Summary HIV incidence rates and 95 % confidence intervals (CIs) were calculated using random effects models. Using the average incidence rate, we modeled HIV prevalence within a simulated cohort of Black MSM (who were all HIV-negative at the start) from ages 18 through 40. Based on five incidence rates totaling 2898 Black MSM, the weighted mean incidence was 4.16 % per year (95 % CI 2.76–5.56). Using this annual incidence rate, our model predicted that 39.94 % of Black MSM within the simulated cohort would be HIV-positive by age 30, and 60.73 % by 40. Projections were similar to HIV prevalence found in community-based samples of Black MSM. High HIV prevalence will persist across the life-course among Black MSM, unless effective prevention and treatment efforts are increased to substantially reduce HIV transmission among this underserved and marginalized population.
PMCID: PMC4718884  PMID: 26267251
HIV/AIDS; Black MSM; Epidemiology; Prevention; HIV incidence; HIV prevalence
4.  Differences in Alcohol Use and Alcohol-Related Problems between Transgender- and Nontransgender-identified Young Adults 
Drug and alcohol dependence  2015;154:251-259.
Little is known about differences in alcohol use and alcohol-related problems between transgender- and nontransgender-identified populations. Using data from a large-scale health survey, we compare the drinking patterns and prevalence of alcohol-related problems of transgender-identified individuals to nontransgender-identified males and females. For transgender-identified people, we examine how various forms of victimization relate to heavy episodic drinking (HED).
Cross-sectional surveys were completed by 75,192 students aged 18–29 years attending 120 post-secondary educational institutions in the United States from 2011–2013. Self-reported measures included alcohol use, alcohol-related problems, victimization, and sociodemographics, including 3 gender-identity groups: transgender-identified individuals; nontransgender-identified males; and nontransgender-identified females.
Compared to transgender-identified individuals, nontransgender-identified males were more likely to report HED in the past 2 weeks (relative risk=1.42; p=0.006); however, nontransgender-identified males and females reported HED on fewer days than transgender-identified people (incidence-rate ratios [IRRs] ranged from 0.28–0.43; p-values<0.001). Compared to transgender-identified people, nontransgender-identified males and females had lower odds of past-year alcohol-related sexual assault and suicidal ideation (odds ratios ranged from 0.24–0.45; p-values<0.05). Among transgender-identified people, individuals who were sexually assaulted (IRR=3.21, p=0.011) or verbally threatened (IRR=2.42, p=0.021) in the past year had greater HED days than those who did not experience those forms of victimization.
Compared to transgender-identified people, nontransgender-identified males and females: have fewer HED occasions (despite nontransgender-identified males having greater prevalence of HED); and are at lower risk for alcohol-related sexual assaults and suicidal ideation. Experiences of sexual assault and verbal threats are associated with greater HED occasions for transgender-identified people.
PMCID: PMC4536098  PMID: 26210734
Transgender; alcohol use; heavy episodic drinking; alcohol-related problems; violence
5.  Does the Clinical Context Improve the Reliability of Rheumatologists Grading Digital Ulcers in Systemic Sclerosis? 
Arthritis Care & Research  2016;68(9):1340-1345.
Digital ulcers (DUs) are often a primary end point in systemic sclerosis (SSc; scleroderma) clinical trials, although the reliability of rheumatologists grading DUs is poor to moderate at best. DU assessment in recent trials has been based upon visual inspection alone, which potentially misses “real‐world” clinical contextual information. Our aim was to investigate whether this clinical information improves the reliability of rheumatologists grading DUs. A secondary aim was to assess agreement between patients and rheumatologists.
Eighty images of a range of digital lesions were collected from patients with SSc with the clinical context: pain (severity and temporal relationship), lesion duration, and discharge (patient reported and clinician observed). Raters received all images either with or without the clinical context, and graded these images (using a custom‐built interface) on an ordinal scale of severity: no ulcer, inactive ulcer, or active ulcer. Patients also graded their lesion(s) on the same scale.
Fifty‐one rheumatologists from 15 countries completed the study (26 without and 25 with context): 4,590 (including 510 repeated) image gradings were obtained. Context did not significantly increase (without and with context) either intra‐ (0.64, 0.71) or interrater (0.32, 0.36) reliability. Pain (visual analog scale and temporal relationship) and discharge (patient reported and clinician observed) were associated with increased lesion severity, and duration with reduced severity. Agreement between individual patients and rheumatologists was poor without and with context (0.19, 0.28).
The overall intra‐ and interrater reliability of DU grading did not significantly improve with the clinical context. Agreement between patients and rheumatologists was poor.
PMCID: PMC5006886  PMID: 26748825
6.  Simulating Nailfold Capillaroscopy Sequences to Evaluate Algorithms for Blood Flow Estimation 
The effects of systemic sclerosis (SSc) – a disease of the connective tissue causing blood flow problems that can require amputation of the fingers – can be observed indirectly by imaging the capillaries at the nailfold, though taking quantitative measures such as blood flow to diagnose the disease and monitor its progression is not easy. Optical flow algorithms may be applied, though without ground truth (i.e. known blood flow) it is hard to evaluate their accuracy.
We propose an image model that generates realistic capillaroscopy videos with known flow, and use this model to quantify the effect of flow rate, cell density and contrast (among others) on estimated flow. This resource will help researchers to design systems that are robust under real-world conditions.
PMCID: PMC4936514  PMID: 24110268
7.  Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long‐Term Treatment Response in Rheumatoid Arthritis 
Jani, Meghna | Chinoy, Hector | Warren, Richard B. | Griffiths, Christopher E. M. | Plant, Darren | Fu, Bo | Morgan, Ann W. | Wilson, Anthony G. | Isaacs, John D. | Hyrich, KimmeL. | Barton, Anne | Prouse, P. J. | Moitra, R. K. | Shawe, D. J. | Nisar, M. | Fairburn, K. | Nixon, J. | Barnes, T. | Hui, M. | Coady, D. | Wright, D. | Morley, C. | Raftery, G. | Bracewell, C. | Bridges, M. | Armstrong, D. | Chuck, A. J. | Hailwood, S. | Kumar, N. | Ashok, D. | Reece, R. | O'Reilly, S. C. | Ding, T. | Badcock, L. J. | Deighton, C. M. | Raj, N. | Regan, M. R. | Summers, G. D. | Williams, R. A. | Lambert, J. R. | Stevens, R. | Wilkinson, C. | Kelly, C. A. | Hamilton, J. | Heycock, C. R. | Saravanan, V. | Cope, A. | Garrood, T. | Ng, N. | Kirkham, B. | Green, M. | Gough, A. | Lawson, C. | Das, D. | Borbas, E. | Wazir, T. | Emery, P. | Bingham, S. | Bird, H. A. | Conaghan, P.G. | Pease, C. T. | Wakefield, R. J. | Buch, M. | Bruce, I. | Gorodkin, R. | Ho, P. | Parker, B. | Smith, W. | Jenkins, E. | Mukhtyar, C. | Gaffney, K. | Macgregor, A. J. | Marshall, T. | Merry, P. | DeSilva, C. | Birrell, F. N. | Crook, P. R. | Szebenyi, B. | Bates, D. | James, D. | Gillott, T. | Alvi, A. | Grey, C. | Browning, J. | McHale, J. F. | Gaywood, I.C. | Jones, A. C. | Lanyon, P. | Pande, I. | Doherty, M. | Gupta, A. | Courtney, P. A. | Srikanth, A. | Abhishek, A. | Das, L. | Pattrick, M. | Snowden, H. N. | Bowden, A. P. | Smith, E. E. | Klimiuk, P. | Speden, D. J. | Naz, S. | Ledingham, J. M. | Hull, R. G. | McCrae, F. | Cooper, A. | Young‐Min, S. A. | Wong, E. | Shaban, R. | Woolf, A. D. | Davis, M. | Hutchinson, D. | Endean, A. | Mewar, D. | Tunn, E. J. | Nelson, K. | Kennedy, T. D. | Dubois, C. | Pauling, J. | Korendowych, E. | Jenkinson, T. | Sengupta, R. | Bhalla, A. | McHugh, N. | O'Neil, T. | Herrick, A. L. | Jones, A. K. | Cooper, R. G. | Dixon, W. G. | Harrison, B. | Buckley, C. D. | Carruthers, D. C. | Elamanchi, R. | Gordon, P. C. | Grindulis, K. A. | Khattak, F. | Raza, K. | Situnayake, K. | Akil, M. | Till, S. | Dunkley, L. | Tattersall, R. | Kilding, R. | Tait, T. | Maxwell, J. | Till, S. | Kuet, K.-P. | Plant, M. J. | Clarke, F. | Fordham, J. N. | Tuck, S. | Pathare, S. K. | Paul, A. | Marguerie, C. P. | Rigby, S. P. | Dunn, N. | Abbas, I. | Filer, C. | Abernethy, V. E. | Clewes, A. R. | Dawson, J. K. | Kitas, G. | Erb, N. | Klocke, R. | Whallett, A. J. | Douglas, K. | Pace, A. | Sandhu, R. | John, H. | Shand, L. | Lane, S. | Foster, H. | Griffiths, B. | Griffiths, I. | Kay, L. | Ng, W.-F. | Platt, P. N. | Walker, D. J. | Peterson, P. | Lorenzi, A. | Friswell, M. | Thompson, B. | Lee, M. | Pratt, A. | Hopkinson, N. D. | Dunne, C. A. | Quilty, B. | Marks, J. | Mukherjee, S. | Mulherin, D. | Chalam, S. V. | Price, T. | Sheeran, T. | Venkatachalam, S. | Baskar, S. | Al- Allaf, W. | McKenna, F. | Shah, P. | Filer, A. | Bowman, S. J. | Jobanputra, P. | Rankin, E. C. | Allen, M. | Chaudhuri, K. | Dubey, S. | Price‐Forbes, A. | Ravindran, J. | Samanta, A. | Sheldon, P. | Hassan, W. | Francis, J. | Kinder, A. | Neame, R. | Moorthy, A. | Bukhari, M. | Ottewell, L. | Palkonyai, E. | Hider, S. | Hassell, A. | Menon, A. | Dowson, C. | Kamath, S. | Packham, J. | Dutta, S. | Price, S. | Roddy, E. | Paskins, Z. | O'Reilly, D. T. | Rajagopal, V. | Bhagat, S. | Chattopadhyay, C. B. | Green, M. | Quinn, D. | Isdale, A. | Brown, A. | Saleem, B. | Foo, B. | Al Saffar, Z. | Koduri, G.
To investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.
A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.
Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.
Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.
PMCID: PMC4843946  PMID: 26109489
8.  Usability evaluation of the progress note construction set. 
OVERVIEW: The Veterans Administration (VA) Computerized Patient Record System (CPRS) is a nationally deployed software product that integrates provider order entry, progress notes, vitals, consults, discharge summaries, problem lists, medications, labs, radiology, transcribed documents, study reports, and clinical reminders. Users rapidly adopted the graphical user interface for data retrieval, but demanded options to typing for data entry. We programmed "point and click" forms that integrate with CPRS individually, but were soon overwhelmed by requests. Subsequently, we developed the Progress Note Construction Set (PNCS); a tool suite that permits subject matter experts without programming skills to create reusable "point and click" forms. In this study, we evaluate the usability of these user-constructed forms. METHODS: An untrained, non-VA subject matter expert used the PNCS to create a graphical form for "skin tear" documentation. Ten VA nurses used the skin tear form to document findings for 7 standardized clinical scenarios. Following each scenario the subjects answered usability questions about the form. RESULTS: The subject matter expert created the skin tear form in 78 minutes. Users found the form to facilitate their data entry (p 0.0265), and to be at least as fast (p 0.0029) and as easy to use as expected (p 0.0166). Average note entry time was 3.4 minutes. CONCLUSION: The PNCS allowed a non-programmer to quickly create a usable, CPRS-integrated point and click form. Users found the subject matter expert s form fast and easy to use. The tool suite is a more scaleable form creation method because capacity is no longer limited by programmer availability.
PMCID: PMC2243587  PMID: 11825158
9.  The content coverage and organizational structure of terminologies: the example of postoperative pain. 
Concepts such as symptoms present specific representational challenges in the EMR. This is because concepts without clear boundaries and external referents such as physical objects can only be examined against other terminology-based concept representation systems. The truth and falsity of such concept representation is therefore relative to the terminology-based systems. Using the concept of acute postoperative pain as an example, we examined three terminology based approaches to representing the concept. Widely varying coverage across existing clinical terminologies was evident, although the common clinical approach to reporting attributes of symptoms provided a useful organizational structure and should be examined in relation to developing terminology and information models.
PMCID: PMC2243894  PMID: 11079900
10.  Investigation of anal function in patients with systemic sclerosis. 
Annals of the Rheumatic Diseases  1996;55(6):370-374.
OBJECTIVE: To investigate anorectal function in women patients with systemic sclerosis (SSc), with and without lower gastrointestinal symptoms. METHODS: Anorectal manometry was performed in 16 patients with SSc: six with no or minimal bowel symptoms, seven with constipation, and three with diarrhoea and faecal incontinence. Eleven healthy women acted as control subjects. Pressure data were recorded via an eight lumen polyvinylchloride water perfused catheter. Station and rapid pull through techniques were used. RESULTS: In the patients with SSc, mean resting pressure, maximal voluntary squeeze effort, and squeeze vector volume were lower, and squeeze asymmetry was greater, compared with the healthy controls. Differences were significant in the subgroup with constipation. CONCLUSION: Radial asymmetry and vector volume parameters provide detailed analysis of segmental anal canal function. Our findings suggest significant segmental deficits in those patients with SSc who have lower gastrointestinal symptoms. The trend towards smaller pressures and squeeze vector volumes in the asymptomatic SSc group suggests subclinical dysfunction in these patients.
PMCID: PMC1010188  PMID: 8694576
11.  Von Willebrand factor, thrombomodulin, thromboxane, beta-thromboglobulin and markers of fibrinolysis in primary Raynaud's phenomenon and systemic sclerosis. 
Annals of the Rheumatic Diseases  1996;55(2):122-127.
OBJECTIVE: To determine whether measurement of different markers of endothelial damage, activation of coagulation, and platelet activation might differentiate between patients with primary Raynaud's phenomenon (PRP), limited cutaneous and diffuse systemic sclerosis (lcSSc and dSSc), and healthy control subjects. METHODS: Under carefully controlled conditions, fasting blood was drawn from 19 healthy control subjects, 10 patients with PRP, 17 with lcSSc and nine with dSSc for measurement of the following: von Willebrand factor (VWF) and soluble thrombomodulin as markers of endothelial damage/activation, thromboxane (as thromboxane B2) and beta-thromboglobulin as markers of platelet activation, and tissue plasminogen activator antigen, tissue plasminogen activator activity and plasminogen activator inhibitor-1 (PAI-1) as markers of fibrinolysis. RESULTS: VWF was increased significantly in patients with SSc, and there was also a linear trend for thromboxane and tissue plasminogen activator antigen (in addition to VWF) to differentiate between different subgroups of patients with Raynaud's phenomenon. Patients with dSSc had the highest values. A combined index of VWF and thromboxane showed a highly significant trend across the four groups studied. CONCLUSION: VWF, and to a lesser extent thromboxane and tissue plasminogen activator antigen, are associated with disease severity in patients with Raynaud's phenomenon. Prospective studies are now required to establish if these parameters can be used as markers of disease progression.
PMCID: PMC1010106  PMID: 8712862
12.  Anticardiolipin, anticentromere and anti-Scl-70 antibodies in patients with systemic sclerosis and severe digital ischaemia. 
Annals of the Rheumatic Diseases  1994;53(8):540-542.
OBJECTIVE--Following observation of weakly positive anticardiolipin (aCL) antibodies in four of eight patients with systemic sclerosis (SSc) and severe digital ischaemia requiring amputation, the association between the presence of these and other antibodies and severe peripheral ischaemia in patients with SSc was examined. METHODS--ACL antibodies (IgG and IgM), anticentromere and anti-Scl-70 antibodies were measured in a further 60 patients with SSc over a one year period. Thirty one of the 68 patients in whom aCL antibodies were assayed had 'severe ischaemia', having suffered digital ischaemia severe enough to warrant amputation (13 patients), surgical debridement or admission for intravenous vasodilator therapy. RESULTS--There was no difference in aCL positivity between those with severe ischaemia and those without, nor between those who had amputations and those who had not. Three of the 31 patients (10%) with severe ischaemia had IgG and eight (26%) IgM aCL antibodies in weak to moderate titre compared to 10 (27%) and 6 (16%) respectively of the remaining patients (p = 0.06 for IgG and p = 0.25 for IgM, Fisher's exact test). Seventeen of the 31 patients (55%) with severe ischaemia were anticentromere antibody positive compared with nine of 37 (24%) without ischaemia (p = 0.01). Six patients with severe ischaemia had anti-Scl-70 antibodies compared with two of the 37 without ischaemia (p = 0.08). CONCLUSIONS--The findings do not support an association between aCL antibodies and severe ischaemia in SSc, but confirm the previously reported association between anticentromere antibodies and severe peripheral ischaemia. Although anti-Scl-70 antibodies were present only in a small number of patients, there was also a tendency for these to be associated with severe ischaemia, suggesting that patients with either anticentromere or anti-Scl-70 antibodies should be considered at risk of digital loss.
PMCID: PMC1005396  PMID: 7944641
14.  Vasculitis in patients with systemic sclerosis and severe digital ischaemia requiring amputation. 
Annals of the Rheumatic Diseases  1994;53(5):323-326.
OBJECTIVES--To document the incidence of histological vasculitis in amputation specimens from patients with severe digital ischaemia secondary to systemic sclerosis (SSc), and to look for an association between anticardiolipin (aCL) antibodies and severe digital ischaemia in SSc. METHODS--This was a retrospective review of patients with SSc who underwent amputation for digital ischaemia over a three year period. RESULTS--Five of nine patients had histological vasculitis, four of whom had aCL antibodies, although these were not present in high titre. CONCLUSION--Vasculitis does occur in SSc, at least in that subgroup with severe peripheral ischaemia. These findings could have implications for treatment of this subgroup of patients with SSc.
PMCID: PMC1005331  PMID: 8017986
16.  Antinuclear antibodies and the diagnosis of systemic lupus erythematosus in patients with acute intermittent porphyria. 
Annals of the Rheumatic Diseases  1990;49(4):246-248.
To investigate the previously postulated association of systemic lupus erythematosus (SLE) and porphyria 38 patients with various types of porphyria were investigated for clinical and laboratory evidence of a connective tissue disease. Antinuclear antibodies (ANAs) were found in 8/15 (53%) patients with acute intermittent porphyria. These patients were more likely to have had a recent acute attack of porphyria, but only one patient had clinical evidence of SLE. Antinuclear antibodies were not found in any patients with latent acute intermittent porphyria or appreciably in any of the other types of porphyria studied. This finding of ANAs in patients with acute intermittent porphyria may explain the previously described association with SLE. Strict diagnostic criteria need to be used in any one patient as these two disorders have many similar clinical manifestations.
PMCID: PMC1004047  PMID: 2339906
17.  Acute intermittent porphyria in two patients on anticonvulsant therapy and with normal erythrocyte porphobilinogen deaminase activity. 
1. Acute intermittent porphyria (AIP) is sometimes termed a 'pharmacogenetic' disease. patients with genetic deficiency of the enzyme porphobilinogen deaminase are liable to develop acute attacks of porphyria if exposed to a variety of drugs. 2. Two patients are reported who had no evidence of deficiency of erythrocyte porphobilinogen deaminase yet developed typical attacks of AIP while on anticonvulsant therapy. 3. Normal activity of erythrocyte porphobilinogen deaminase does not completely exclude porphyria. 4. Acute porphyria should be suspected if clinical deterioration occurs during therapy with anticonvulsants, or other porphyrinogenic drugs, even in the absence of an underlying genetic defect in haem synthesis in peripheral blood cells.
PMCID: PMC1379729  PMID: 2497768

Results 1-18 (18)