Diabetes insipidus revealing primary malignant non-Hodgkin''s lymphoma of bone]

Renal histology is increasingly used as a guide for therapy and prognosis in SLE but data in children are few and/or short-term. We assessed renal histological features in 19 children with SLE to determine whether these features are useful in predicting long-term outcome. Mean age at biopsy was 10 +/- 1.7 years old, male to female ratio was 1:2.8. Fourteen patients (73%) had diffuse proliferative lupus nephritis. Renal histology was evaluated using an activity index (AI) and chronicity index (CI). Clinical assessment of renal function at biopsy and outcome were graded according to urinalysis and serum creatinine. Renal function at biopsy correlated well with AI (p < 0.001) but not CI. At short-term follow-up (30 months), 3 patients had died from sepsis and another 2 reached end-stage renal disease. CI predicted poor clinical outcome, i.e. death or renal failure (p < 0.005) but AI did not. At long-term follow-up (mean 92.1 +/- 26.8 months) only one more patient reached end-stage renal disease. In others renal function assessment showed improvement or were stable. Neither CI nor AI correlated with clinical outcome. We conclude that although AI correlates well with renal function at biopsy and CI with short-term prognosis, neither can predict long-term outcome. Treatment may have altered the natural course of disease in these patients.     

Technetium-99m-HMPAO brain SPECT in systemic lupus erythematosus with CNS involvement

Functional brain SPECT is playing an increasingly important role in evaluating CNS conditions in patients with systemic lupus erythematosus (SLE). However, SPECT findings varied in different studies because of their small population. Furthermore, earlier researchers, being restricted by the resolution of the camera, might not have been able to evaluate deep-seated nuclei such as the basal ganglia and thalamus. In this study, we describe the different patterns of SPECT findings in SLE patients with CNS involvement. METHODS: Seventy-two SLE patients (aged 14-67 yr; mean 33.2 yr) were divided into three groups: Group 1 with definite neuro-psychiatric disorder (including stroke, seizures and psychosis); Group 2 with minor neuropsychiatric disorders (headache, dizziness and recent memory impairment); and Group 3 without any neuropsychiatric symptoms or signs. Ninety minutes after injection of 1110 MBq 99mTc-HMPAO, brain SPECT was performed using a dual-head camera and fan-beam collimator. In addition, MRI and an electroencephalography (EEG) were also performed. RESULTS: SPECT findings were normal in 87% of the Group 3 patients and abnormal in all Group 1 patients; 84.6% of the Group 2 patients had abnormal SPECT findings. The parietal, frontal and temporal lobes were the most common areas of CNS involvement. Parietal lobes were involved in 95.6% of Group 1 patients and 80.7% in Group 2 patients. Frontal lobes were involved in 56.5% of Group 1 patients and 65.3% of Group 2 patients. Temporal lobes were involved in 56.5% of Group 1 patients and 46.1% of Group 2 patients. The basal ganglion was involved in about 30% of Group 1 patients and 11.5% of Group 2 patients, while the thalamus and cerebellum were less involved in neuropsychiatric SLE. MR images showed less sensitivity in the detection of CNS involvement than the SPECT and were normal in 27.3% of patients with definite neuropsychiatric disorders. The EEG and anticardiolipin antibody did not correlate well to the clinical diagnosis. CONCLUSION: HMPAO brain SPECT had the best correlation with the clinical diagnosis and may provide additional and objective information on SLE patients with potential CNS involvement.     

Identification of patients with autosomal dominant polycystic kidney disease at highest risk for end-stage renal disease

To identify those potential factors that, early in the course of disease, mark a population of patients with autosomal dominant polycystic kidney disease (ADPKD) who have worse renal survival, survival analysis and risk ratio calculation for 1215 ADPKD patients were performed. Survival times were calculated as time to dialysis, transplantation, or death. Risk ratios were calculated using the Cox proportional hazards model. Three hundred eighty-eight patients entered end-stage renal disease and 205 patients died. ADPKD2 subjects had longer renal survival than ADPKD1 subjects (median survival, 68 versus 53 yr; P < 0.0005; risk ratio, 2.5). Women had significantly better renal survival than men (56 versus 52 yr; P < 0.0001; risk ratio, 1.6). Subjects who were diagnosed before age 30 and those who developed hypertension before age 35 had worse renal survival than those subjects who were diagnosed after age 30 or those who remained normotensive after age 35, respectively (age of diagnosis: 49 versus 59 yr; P < 0.0001; risk ratio, 3.2; hypertension: 51 versus 65 yr; P < 0.0001; risk ratio, 4.4). Similarly, those who had an episode of gross hematuria before age 30 had a worse renal outcome than those who did not (49 versus 59 yr; P < 0.0001; risk ratio, 2.6). We have also calculated risk ratios for a combined model. When therapeutic interventions become available for this disease, these populations with high risk ratios should be considered for such interventions.     

Predictors of success on the ARRT''s MRI exam

Our objective was to determine the effect of 1 year low-dose cyclosporine A (CSA) treatment on disease activity and renal involvement in systemic lupus erythematosus (SLE). Patients included in the pilot study had an active form of the disease as defined by the SLE Disease Activity Index (SLEDAI). Main organ involvement was represented by lupus nephritis classified in repeated renal biopsies. Eleven patients with SLE were enrolled in the study. In eight of them, previous therapy with cyclophosphamide or azathioprine had to be interrupted due to serious adverse reaction or low efficacy. Nine patients experienced clinical nephrotic syndrome, and two the nephritic syndrome. After 12 months of CSA treatment, the mean SLEDAI score had decreased significantly from 26.18 to 4.00 (P < 0.01). Similarly, the titre of antinuclear and anti-dsDNA antibodies had dropped significantly (P < 0.01). Proteinuria decreased rapidly from 9.10 to 1.70 g/24 h (P < 0.001). According to the WHO classification of renal biopsies, three patients had their class altered from IV to III in response to CSA treatment and five patients had changed the status from the high severity grade to the mild. The adverse reactions included hypertension (45%), gingival hyperplasia (18%) and hirsutism (9%). No significant increase in serum creatinine or any CSA related toxic changes were found in renal biopsies. The favourable response observed in patients with active SLE and with major renal involvement strongly suggests that low-dose CSA is a potent drug as much for the reduction of the disease activity as for lupus nephropathy treatment.     

Long-term prognosis of Henoch-Sch?nlein nephritis in adults and children. Italian Group of Renal Immunopathology Collaborative Study on Henoch-Sch?nlein purpura

BACKGROUND: The aim of this multicentre collaborative study was to compare the progression of renal disease in children and adults with Henoch-Sch?nlein purpura (HPS) nephritis selected on the basis of IgA-dominant renal deposits and biopsy material available for review. METHODS: The analysis was performed in 152 patients (95 adults and 57 children < 16 years old at diagnosis) with a follow-up (> or = 1 year up to 20 years (4.9 +/- 3.4 years in adults and 4.8 +/- 3.9 years in children). RESULTS: Renal histology and clinical presentation were similar in both age groups: crescents were found in 36% of adults and 34.6% of children (in only 2.7% of adults and 1.9% of children involving > 50% of glomeruli), nephrotic-range proteinuria in 29.5% of adults and 28.1% of children and functional impairment in 24.1% of adults and 36.9% of children. The outcome was similar for both age groups (remission, 32.5% of adults and 31.6% of children; renal function impairment, 31.6% of adults and 24.5% of children). Endstage renal disease was observed in 15.8% of adults and in 7% of children. Renal function survival at 5 years was not significantly different in the two groups (85% in adults and 95% in children) and at 10 years it was approximately 75% in both groups. None of the children died and adult survival was 97% at 5 years. In adults at presentation, renal function impairment (P < 0.02) as well as proteinuria higher than 1.5 g/day (P < 0.02) and hypertension (P < 0.001) were negative prognostic factors. Multivariate analysis stressed the main statistical relevance of proteinuria (relative risk 2.37, P < 0.02). Conversely, in children no definite level of proteinuria, hypertension or other data were found to be associated with poor prognosis. CONCLUSIONS: Among patients with a clinical presentation which warrants renal biopsy, HSP nephritis has a similar prognosis in children and adults. The evolution is more predictable in adults than in children.     

Evaluation and management of bilateral renal artery stenosis in children: a case series and review

This report describes the clinical course, diagnostic evaluation and management of six children with bilateral renal artery stenosis (RAS) and concurrent narrowing of the abdominal aorta. Except for one child with active arteritis, the others were asymptomatic. There were no clinical or laboratory features suggesting the etiology of hypertension in four of six patients, and diagnostic procedures, including Doppler duplex ultrasound and captopril scintigraphy, were unreliable in screening for such hypertension. Abdominal aortography and selective renal angiography confirmed the diagnosis of bilateral RAS and associated anatomical alterations of the aorta and its branches. The hypertension was severe and minimally responsive to antihypertensive agents. It was cured or improved after percutaneous transluminal angioplasty (PTA) of three vessels in two children with mid-vessel stenoses, while hypertension persisted after PTA of two mid-vessel stenoses in a third child and one vessel with ostium stenosis in a fourth child. Autotransplantation of seven kidneys in four children resulted in cure of significant improvement of the hypertension. Renal function was preserved in all children during a mean follow-up time of 41 months. Based on illustrative data from these six children, as well as information from a review of the literature, this report discusses the key diagnostic issues and stresses the potential advantages of renal autotransplantation in selected children with this disorder.     

Myocardial involvement in systemic lupus erythematosus. A noninvasive study of left ventricular function

A relatively high incidence of heart failure is noted among patients with systemic lupus erythematosus (SLE) without clearly defined clinical causes. To evaluate left ventricular performance in patients with SLE without evidence of cardiovascular disease, noninvasive measurement of the systolic time intervals was carried out. Simultaneous recording of the electrocardiogram, phonocardiogram and carotid arterial pulsation were obtained in 25 patients with systemic lupus erythematosus and compared with 22 normal subjects. The patients with SLE had a shorter left ventricular ejection time (P less than 0.05), a longer pre-ejection period (P less than 0.02) and an increased ratio of pre-ejection period/left ventricular ejection time (P less than 0.005). These abnormalities on ventricular function were independent of age, duration of the disease, hypertension, renal involvement, anemia, immunologic activity and corticosteroid treatment. Several etiologic possibilities are discussed and the clinical usefulness of this method to detect and follow-up the cardiac dysfunction in systemic lupus erythematosus is emphasized.     

Continuous ambulatory measurement of blood pressure in children--personal experience

Ambulatory blood pressure monitoring (ABPM) during normal daily activities and during night, when the patient is asleep, is a new method of measuring blood pressure (BP) in children, used for better diagnosis and treatment of hypertension. Compared to casual BP measurements, it documents normal daily BP variations, BP during sleep, the influence of emotional and physical stress on BP and is a better predictor of hypertension associated with end-organ damage. However, the experience in ABPM in children is still limited. In our country ABPM has been used since recently, and first results are referred to children with end-stage renal failure. SUBJECTS AND METHODS: ABPM was performed in two groups of children: group A consisted of 61 children, aged 14.3 +/- 2.9 (mean +/- SD) yrs in whom intermittent outpatient BP measurements (for at least 3 months) suggested the diagnosis of hypertension (according to the data of Second Task Force); group B consisted of 52 patients (pts), aged 12.8 +/- 4.6 yr with renal disease. Four pts from group A (6.6%) and 20 pts from group B (38.5%) received antihypertensive therapy (captopril, nifedipine, furosemide and propranolol ). All children from group A and half of the children from group B had normal renal function. Eighteen pts from group B were on chronic haemodialysis (34.6%). Blood pressure was recorded during a 24-hour period except in haemodialyzed pts (48 h) (Table 1). Results of BP measurements are presented as the mean values of BP during a 24-hour period, during normal daily activities and during sleep. We used the age- and gender-appropriate 95th percentile from the Task Force Study as the daytime upper-limit of normal and 10% lower for the upper-limit at night. According to BP load (the percentage of BPs exceeding the upper limits of normal for age), children were assumed to have mild-to-moderate hypertension (BP load between 20% and 40%) or severe hypertension (BP load more than 40%). The success of antihypertensive therapy was evaluated after 1-3 months in 11 pts (twice in 10 pts and three times in one pt). RESULTS: In group A 39.4% of pts were normotensive and 36.1% were without antihypertensive therapy, 58.4% of normotensive and 40.5% of hypertensive pts had blunted circadian BP rhythm (nocturnal BP reduction of less than 10% of diurnal values) (Graph. 1). In group B 38.5% of pts were normotensive and 27% were without antihypertensive therapy. In the group of normotensive pts alteration of circadian BP rhythm was found in 40% of pts with normal renal function, 80% of pts with chronic renal failure and in 100% of pts with terminal renal failure, while in the hypertensive group, altered circadian BP rhythm had 68%, 100% and 92% of pts, respectively (Graph 2). Mild-to-moderate hypertension had 54% of hypertensive pts from group A and 37.5% of hypertensive pts from group B. Severe hypertension was more frequent in group B (62.5%) comparing to group A (46%). The effectiveness of antihypertensive therapy was assessed in 11 pts. In 69.2% of pts BP became normal or was significantly decreased, in 23.1% of pts BP was not changed and 7.7% of pts had higher values of BP. DISCUSSION: ABPM is very useful for diagnosing white coat hypertension. Like other authors, we have pointed out that more than one third of pts who were hypertensive according to usual BP measurements had normal 24-hour BP and we classified them as white coat hypertensives. More than a half of the pts had blunted circadian BP rhythm, and as it is not certain whether they will become hypertensive in adulthood they should be periodically controlled. There are several proofs that results of ABPM have a better correlation with hypertensive end-organ damage; therefore ABPM is used for assessing the severity of hypertension. In our former work, we showed excellent correlation of BP with left ventricular mass index in children with end-stage renal failure. (ABSTRACT TRUNCATED)     

From genes to development: phenogenetic contributions to developmental biology in Soviet Russia from 1917 to 1967

A prospective study of all new cases of chronic renal failure (CRF) including inservice referrals was done at our hospital over a period of 1 year from May 1994 to April 1995. The diagnosis of CRF was based on clinical, laboratory, and radiological features. Kidney biopsies were done when indicated. The patients were subdivided into various etiologic groups of primary renal disease according to standard criteria. There were a total of 835 cases of CRF with a median age of 43 years (range 10 days to 90 years); 67.8% of them were men. Glomerulonephritis (28.6%), diabetic nephropathy (23.2%), and interstitial nephritis (16.5%) were the most common causes of CRF, followed by obstructive nephropathy (6.4%), benign nephrosclerosis (4.1%), and polycystic kidney disease (2%). However, in patients more than 40 years of age, diabetic nephropathy was the most common cause (36.8%). The cause of CRF was unknown in 16.2% of the cases. One hundred twenty-one patients (14.5%) had an acute deterioration of their underlying renal dysfunction at presentation. This was most commonly due to accelerated hypertension (26.1%), infection (22.4%), volume depletion (20.1%), and drugs (14.9%). Anti-inflammatory drugs were the most common drugs responsible for the acute decline in renal function. One year after their initial presentation, of the 512 patients (61.3%) with end stage renal disease, 12.5% had died, 17% had received a kidney allograft, 12.7% were on some form of maintenance dialysis, and 295 patients were lost to follow-up. Of the 323 patients with less severe illness, 7 died, 209 were on outpatient treatment, and 107 patients were lost to follow-up. We conclude that the pattern of CRF in India does not differ greatly from that in the developed countries. However, it carries a poorer prognosis due to late referral and limited availability and affordability of renal replacement therapy in India.     

Screening for renovascular hypertension in a population with relatively low prevalence

OBJECTIVE: To evaluate the accuracy and cost-efficacy of the diagnostic procedure and treatment for renovascular hypertension. SETTING AND PATIENTS: A total of 519 patients referred to the university clinic for hypertension were screened for renovascular hypertension with 405 captopril challenge tests (CCT) and 450 captopril renographies (CRG). INTERVENTIONS: Abdominal angiography was performed on 84 patients for positive screening. Fifteen patients underwent angiography for a sole suspicious clinical presentation. The angiography revealed 17 renal artery stenoses and five occlusions in 20 patients. Fifteen technically successful angioplasties and three nephrectomies were performed. RESULTS: In the patients who underwent angiography, CCT had a specificity of 39% and a sensitivity of 67% for renovascular hypertension. CRG had a sensitivity of 100% and a specificity of 68%. In the whole study population, the estimated specificity of CCT was 88% and that of CRG 95%. Invasive treatment reduced systolic/diastolic blood pressure from 157/99 to 140/87 mmHg and the number of antihypertensive drugs used from 2.6 to 1.4 in 16 patients (mean age 49 years). Angiotensin converting enzyme (ACE) inhibition was effective in four elderly patients. Cost-efficacy analysis Screening with CRG and invasive treatment cost US$15400 per successful invasive treatment Equally effective pharmacological treatment would have cost US$10400. Limiting the screening with CRG to the 173 patients with no obvious renal parenchymal disease and with hypertension at a younger age (< or =30 years) or unresponsive to two antihypertensive drugs (diastolic blood pressure > 90 mmHg) would have yielded a prevalence of 12% and missed only one elderly patient who responded to ACE inhibition. The limited screening, along with invasive treatment, would have cost US$7300 per patient CONCLUSIONS: CRG is superior to CCT for screening of renovascular hypertension. Screening with CRG is cost-effective when limited to patients with no obvious renal parenchymal disease and with hypertension that does not respond to two antihypertensive drugs or is detected in patients no older than 30 years.     

Subdural haemorrhages in infants: population based study

OBJECTIVES: To identify the incidence, clinical outcome, and associated factors of subdural haemorrhage in children under 2 years of age, and to determine how such cases were investigated and how many were due to child abuse. DESIGN: Population based case series. SETTING: South Wales and south west England. SUBJECTS: Children under 2 years of age who had a subdural haemorrhage. We excluded neonates who developed subdural haemorrhage during their stay on a neonatal unit and infants who developed a subdural haemorrhage after infection or neurosurgical intervention. MAIN OUTCOME MEASURES: Incidence and clinical outcome of subdural haemorrhage in infants, the number of cases caused by child abuse, the investigations such children received, and associated risk factors. RESULTS: Thirty three children (23 boys and 10 girls) were haemorrhage. The incidence was 12.8/100 000 children/year (95% confidence interval 5.4 to 20.2). Twenty eight cases (85%) were under 1 year of age. The incidence of subdural haemorrhage in children under 1 year of age was 21.0/100 000 children/year and was therefore higher than in the older children. The clinical outcome was poor: nine infants died and 15 had profound disability. Only 22 infants had the basic investigations of a full blood count, coagulation screen, computed tomography or magnetic resonance imaging, skeletal survey or bone scan, and ophthalmological examination. In retrospect, 27 cases (82%) were highly suggestive of abuse. CONCLUSION: Subdural haemorrhage is common in infancy and carries a poor prognosis; three quarters of such infants die or have profound disability. Most cases are due to child abuse, but in a few the cause is unknown. Some children with subdural haemorrhage do not undergo appropriate investigations. We believe the clinical investigation of such children should include a full multidisciplinary social assessment, an ophthalmic examination, a skeletal survey supplemented with a bone scan or a skeletal survey repeated at around 10 days, a coagulation screen, and computed tomography or magentic resonance imaging. Previous physical abuse in an infant is a significant risk factor for subdural haemorrhage and must be taken seriously by child protection agencies.     

The etiology of idiopathic sudden sensorineural hearing loss. Experimental herpes simplex virus infection of the inner ear

PURPOSE: To evaluate dimercaptosuccinic acid (DMSA) scintigraphy and urography in the detection of renal involvement in children with urinary tract infection (UTI) in order to identify patients with a high risk of developing renal damage. MATERIAL AND METHODS: A total of 157 children (median age 0.4 years, range 5 days to 5.8 years) with first-time symptomatic UTI were examined scintigraphy (with an assessment of renal area involvement) and urography at the time of UTI and 1 year later. All evaluations were made blindly. RESULTS: Of the total 314 kidneys, 80 (25%) were abnormal at initial scintigraphy. Of these 80 kidneys, 44 (55%) had normalized at follow-up. Of the 234 initially normal kidneys, 29 (12%) were abnormal at follow-up. One year after UTI, abnormalities were seen in 59 children at scintigraphy and in 18 children at urography. Renal area involvement was larger and split function abnormalities more common in kidneys that were abnormal at both scintigraphy and urography than in kidneys with only scintigraphic abnormalities. CONCLUSION: Quantitation of renal area involvement and split renal function at early scintigraphy would seem to be useful in identifying patients at risk of developing renal damage. Urography at 1 year after infection identified mainly those with the most severe scintigraphic abnormalities. The clinical importance of scintigraphic abnormalities that are not confirmed by urography is not known.     

Tuberculosis among Filipino patients with systemic lupus erythematosus

A retrospective review of the clinical records of 54 patients with systemic lupus erythematosus (SLE) and documented tuberculosis (TB) infection seen at the University of Santo Tomas Hospital was accomplished. There were 53 women and one man, with a mean age of 32.2 +/- 10 years and a total of 57 TB occurrences. Pulmonary involvement was recorded in 42 (74%): upper lungfield in 25, mid to lower lungfield in 7, and miliary pattern or diffuse infiltrates in 10. TB arthritis was noted in 8, osteomyelitis in 4, and soft tissue abscesses in 4. Central nervous system involvement consisted of brain abscesses (tuberculomas) in two and meningitis in one. Two patients each had TB lymphadenitis, genitourinary TB, ileocecal TB, and TB peritonitis. Hepatobiliary and cutaneous TB occurred in one patient each. Eight of 10 patients with disseminated or miliary TB died primarily of respiratory failure; six of these eight patients also had some form of extrapulmonary involvement. Using the Wilcoxon rank-sum test, there were significant differences in the mean SLE Disease Activity Index (SLEDAI) and Severity of Disease Index (SDI) scores between those with limited TB (SLEDAI 24 +/- 7 SD; SDI 19 +/- 18 SD) versus those with extensive TB (SLEDAI 41 +/- 16 SD; SDI 36 +/- 21 SD), P < .05. There was no significant difference in the average daily prednisone dose (mg) between those with limited TB (25 +/- 17 SD) versus those with extensive TB (31 +/- 16 SD). The contributory role of tuberculous infection in the morbidity and mortality of patients with SLE must be emphasized, especially in areas endemic for TB.     

Social support and parental adjustment to pediatric cancer.

Assessed the psychosocial adjustment of 107 23–58 yr old parents whose children had cancer using the Psychosocial Adjustment to Illness Scale. Ss whose child had died showed poorer adjustment than Ss whose child was in treatment or had completed treatment. Ss over 30 yrs of age showed better adjustment than younger Ss. Different patterns of association between 11 sources of social support and adjustment were found. Psychosocial adjustment of Ss with a child in treatment was correlated more frequently with perceived social support than for other Ss. Results suggest that particular attention should be paid to the psychosocial adjustment of young bereaved parents. (7 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporomandibular joint derangement after air bag deployment: report of two cases

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.     

Antineutrophil cytoplasmic antibodies in primary Sj?gren's syndrome: prevalence and clinical significance

OBJECTIVE: To evaluate the prevalence of cytoplasmic (c) and perinuclear (p) antineutrophil cytoplasmic antibodies (ANCA) in patients with primary Sjogren's syndrome (SS), and to correlate the presence of ANCA with extraglandular and immunological manifestations related to SS. METHODS: In a cross-sectional study, we included 82 consecutive patients (75 female and seven male; mean age 61 yr; range 33-87 yr) attending our unit. All patients fulfilled four or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Extraglandular manifestations such as arthralgia and/or arthritis, Raynaud's phenomenon, autoimmune thyroiditis, peripheral neuropathy, renal involvement and cutaneous vasculitis were also recorded. Serum samples were examined by indirect immunofluorescence (IIF) and by ELISA using as substrates myeloperoxidase (MPO) and proteinase 3 (PR3). RESULTS: ANCA were detected in nine (11%) patients: seven had pANCA and two an atypical pattern. These two atypical ANCA became cANCA when paraformaldehyde fixation was applied. ELISA findings showed that two patients had antibodies against MPO, and no patient had antibodies to PR3. The most common extraglandular manifestations in the ANCA-positive patients were articular involvement in six (66%) patients, peripheral neuropathy in five (55%), Raynaud's phenomenon in four (44%) and cutaneous vasculitis in four (44%). Of the four patients with cutaneous vasculitis and ANCA, two had a mononuclear inflammatory vascular disease (MIVD) in the biopsy specimen. When compared with patients without ANCA, those with these antibodies had a higher prevalence of cutaneous vasculitis (44% vs 8%, P = 0.01), Raynaud's phenomenon (44% vs 8%, P = 0.01) and peripheral neuropathy (55% vs 7%, P < 0.001). CONCLUSION: ANCA positivity can be found in patients with primary SS and its detection is associated with the presence of clinical manifestations attributable to vascular involvement (cutaneous vasculitis, peripheral neuropathy and Raynaud's phenomenon).     

Systemic lupus erythematosus in childhood correlations between changes in disease activity and serum complement levels

Serial complement component (C3 and C4) determinations were performed in 26 children with systemic lupus erythematosus. Twenty-one children with SLE had 52 episodes of C3 depression (mean duration 25 weeks); only 11 of these children had active nephritis when serum concentrations of complement were depressed. Fourteen children had active rash associated with low C3; in seven of these children rash was the only clinical evidence of disease activity. Ten children had active CNS disease; in seven children the CNS involvement correlated with low C3. In general, variations in serum concentrations of C4 did not reflect changes in SLE activity which were not reflected by changes in serum concentrations of C3. Serum C4 occasionally remained depressed longer than C3, perhaps reflecting continuing subclinical disease activity. Increased C3 occurred in 18 of 26 children as doses of corticosteroid were increased, in six of 14 when cyclophosphamide was added, and in two children when hydroxychloroquine was added. Our findings suggest that a wide variety of manifestations of childhood SLE may produce hypocomplementemia. In addition to renal disease, variations in serum concentrations of C3 and C4 can reflect, or occasionally predict, changes in rash and CNS disease.     

Familial clustering of end-stage renal disease in blacks with lupus nephritis

The factors that determine a patient's susceptibility to specific target organ involvement in systemic lupus erythematosus (SLE) remain unknown. Lupus nephritis can be a particularly devastating complication, with an increased mortality and the risk of progressive renal damage resulting in end-stage renal disease (ESRD). This analysis was performed to determine whether renal disease aggregated in select families or was a sporadic complication in patients with SLE. We compared the family history of ESRD in 50 patients with SLE complicated by lupus nephritis with 37 controls who had SLE but lacked nephritis after a mean follow-up duration of more than 11 years. The frequency of relatives with ESRD in the lupus nephritis cases was compared with that in controls using Fisher's exact test (significance at P < or = 0.05). Fifty percent (25) of the 50 lupus nephritis patients were black and 50% (25) white, in contrast to 35% (13) and 65% (24) of the 37 lupus non-nephropathy controls, respectively. A first-, second-, or third-degree relative with ESRD was present in 16% (eight) of the 50 lupus nephritis cases and in 0% of the 37 SLE non-nephropathy controls (P = 0.019, Fisher's exact test, two-tail). Twenty-eight percent (seven) of the 25 black patients with lupus nephritis had relatives with ESRD compared with 0% of the 13 black lupus non-nephritis controls (P = 0.07). Only one of the eight relatives with ESRD had SLE or a collagen vascular disease. Lupus nephritis patients and the non-nephritis controls had similar ages (mean +/- SD: 38.5 +/- 10.0 years v 46.6 +/- 11.8 years; P = 0.28), family sizes (6.27 +/- 2.61 first-degree relatives v 6.35 +/- 3.25 first-degree relatives; P = 0.16), and duration of SLE (9.26 +/- 5.94 years v 11.35 +/- 6.43 years; P = 0.60). Familial clustering of ESRD was observed in black patients with SLE who had nephritis. This was unlikely to be related to differences in patient age, family size, or duration of SLE. This data, coupled with the known familial aggregation of ESRD in blacks with hypertensive and diabetic ESRD, supports the contention that genetic factors contribute to the familial clustering. The presence of relatives with etiologies of ESRD other than SLE suggests that there is an inherited susceptibility to progressive renal failure, independent of the etiology of ESRD.     

Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study

OBJECTIVES: The aim of the present investigation was to redefine the clinicopathologic profile of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC), with special reference to disease progression and left ventricular (LV) involvement. BACKGROUND: Long-term follow-up data from clinical studies indicate that ARVC is a progressive heart muscle disease that with time may lead to more diffuse right ventricular (RV) involvement and LV abnormalities and culminate in heart failure. METHODS: Forty-two patients (27 male, 15 female; 9 to 65 years old, mean [+/-SD] age 29.6 +/- 18) from six collaborative medical centers, with a pathologic diagnosis of ARVC at autopsy or heart transplantation, and with the whole heart available, were studied according to a specific clinicomorphologic protocol. RESULTS: Thirty-four patients died suddenly (16 during effort); 4 underwent heart transplantation; 2 died as a result of advanced heart failure; and 2 died of other causes. Sudden death was the first sign of disease in 12 patients; the other 30 had palpitations, with syncope in 11, heart failure in 8 and stroke in 3. Twenty-seven patients experienced ventricular arrhythmias (ventricular tachycardia in 17), and 5 received a pacemaker. Ten patients had isolated RV involvement (group A); the remaining 32 (76%) also had fibrofatty LV involvement that was observed histologically only in 15 (group B) and histologically and macroscopically in 17 (group C). Patients in group C were significantly older than those in groups A and B (39 +/- 15 years vs. 20 +/- 8.8 and 25 +/- 9.7 years, respectively), had significantly longer clinical follow-up (9.3 +/- 7.3 years vs. 1.2 +/- 2.1 and 3.4 +/- 2.2 years, respectively) and developed heart failure significantly more often (47% vs. 0 and 0, respectively). Patients in groups B and C had warning symptoms (80% and 87%, respectively, vs. 30%) and clinical ventricular arrhythmias (73% and 82%, respectively, vs. 20%) significantly more often than patients in group A. Hearts from patients in group C weighed significantly more than those from patients in groups A and B (500 +/- 150 g vs. 328 +/- 40 and 380 +/- 95 g, respectively), whereas hearts from both group B and C patients had severe RV thinning (87% and 71%, respectively, vs. 20%) and inflammatory infiltrates (73% and 88%, respectively, vs. 30%) significantly more often than those from group A patients. CONCLUSIONS: LV involvement was found in 76% of hearts with ARVC, was age dependent and was associated with clinical arrhythmic events, more severe cardiomegaly, inflammatory infiltrates and heart failure. ARVC can no longer be regarded as an isolated disease of the right ventricle.     

Causes of death in autosomal dominant polycystic kidney disease

To determine the causes of death in autosomal dominant polycystic kidney disease (ADPKD) patients and to examine whether the extrarenal manifestations of ADPKD influence the causes of death, the medical records of 129 patients who died between 1956 and 1993 were reviewed; 58% of the 129 patients had an autopsy performed. Seventy-seven percent died after reaching ESRD. The mean age at death increased from 51 yr for those who died before 1975 to 59 yr for those who died after 1975, reflecting the introduction of renal replacement therapies. The most common cause of death before 1975 was infection (30%), followed by uremia (28%) and cardiac disease (21%); after 1975, these were cardiac disease (36%) and infection (24%). Infection was equally prevalent before and after 1975, presenting as sepsis in 94% and directly relating to ADPKD in 47% of these patients. Underlying factors for cardiac death were cardiac hypertrophy, seen in 89% of all autopsied patients, and coronary artery disease, seen in 81%. A neurologic event was the cause of death in 12% of patients; these were ruptured intracranial aneurysm in 6%, hypertensive intracranial hemorrhage in 5%, and ischemic stroke in 1%. The mean age of those who died of ruptured intracranial aneurysm was 37 yr. No patient died of renal cancer. Liver cysts were the most common extrarenal manifestation, seen in 70% of the autopsied cases; cysts in other organs were very rare. Colonic diverticula were found in 21%. Thus, the renal and extrarenal manifestations of ADPKD are important contributors to morbidity and mortality.