Poland syndrome associated with renal agenesis

Poland syndrome is characterized by unilateral aplasia or hypoplasia of the sternocostal portion of the pectoralis major muscle and ipsilateral syndactyly. In some cases other associated anomalies, including renal malformations, dextrocardia, and vertebral abnormalities, have been reported. We report a 7-month-old girl with Poland syndrome who also presented with ipsilateral renal agenesis. This report suggests that renal structural anomaly may be an integral part of this syndrome. We recommend renal imaging studies be performed on all children with Poland syndrome. Received: 23 July 2001 / Revised: 23 October 2001 / Accepted: 23 October 2001     

Intraoperative total serum calcium levels,unlike intraoperative intact PTH levels,do not correlate with cure of hyperparathyroidism

BACKGROUND: Intraoperative intact parathyroid hormone (iPTH) monitoring is useful in the operative management of hyperparathyroidism. Recent studies suggest that measurement of intraoperative total serum calcium (TSC) levels may be a more cost effective and readily available method of intraoperative guidance during neck dissection than iPTH levels, the gold standard. We compared the accuracy of intraoperative TSC to iPTH in predicting surgical cure during parathyroidectomy. PATIENTS AND METHODS: From September 1, 2001 to October 31, 2002, 88 parathyroidectomies were performed. iPTH and TSC were measured at the start of the operation, and at 5 and 10 min after gland removal. Data were compared, and trends were analyzed with respect to removal of abnormal parathyroid tissue as confirmed by pathology. One-way analysis of variance was used to determine if decreases in TSC were significant. RESULTS: The mean baseline iPTH level (418 +/- 610 pg/ml) dropped by 70% 5 min after removal of the abnormal glands (86 +/- 102 pg/ml) and by 85% at 10 min (39 +/- 39 pg/ml). The mean baseline TSC level (10.0 +/- 0.8 mg/dl) dropped by 4% at 5 min after removal of the abnormal glands (9.6 +/- 0.9 mg/dl) and remained at 4% at 10 min (9.6 +/- 0.8 mg/dl). iPTH dropped by > or =50% in 73 patients (83%) at 5 min and in 87 patients (99%) at 10 min after gland resection. TSC decreased below baseline at 5 min and remained below baseline at 10 min in only 47 patients (54%). In the remaining patients, intraoperative TSC changes were less predictable and did not respond consistently to resection of abnormal glands. CONCLUSIONS: The decreases in TSC during parathyroidectomy, if present, are minimal. Unlike iPTH levels, TSC levels do not consistently decrease at 5 and 10 min after gland resection. While attractive in terms of cost and availability, intraoperative TSC levels are not clinically reliable in confirming removal of abnormal parathyroid tissue.     

Vascular hyperpermeability as a hallmark of phacomatoses: is the etiology angiogenesis related to or comparable with mechanisms seen in inflammatory pathways? Part II: angiogenesis- and inflammation-related molecular pathways,tumor-associated macrophages,and possible therapeutic implications: a comprehensive review

Phacomatoses are a special group of familial hamartomatous syndromes with unique neurocutaneous manifestations as well as characteristic tumors. Neurofibromatosis type 2 (NF2) and tuberous sclerosis complex (TSC) are representatives of this family. A vestibular schwannoma (VS) and subependymal giant cell tumor (SGCT) are two of the most common intracranial tumors associated with these syndromes, related to NF2 and TSC, respectively. These tumors can present with an obstructive hydrocephalus due to their location adjacent to or in the ventricles. Remarkably, both tumors are also known to have a unique association with elevated protein concentrations in the cerebrospinal fluid (CSF), sometimes in association with a non-obstructive (communicating) hydrocephalus. Of the two, SGCT has been shown to be associated with a predisposition to CSF clotting, causing a debilitating recurrent shunt obstruction. However, the exact relationship between high protein levels and clotting of CSF remains unclear, nor do we understand the precise mechanism of CSF clotting observed in SGCT. Elevated protein levels in the CSF are thought to be caused by increased vascular permeability and dysregulation of the blood–brain barrier. The two presumed underlying pathophysiological processes for that in the context of tumorigenesis are angiogenesis and inflammation. Both these processes are correlated to the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin pathway which is tumorigenesis related in many neoplasms and nearly all phacomatoses. In this review, we discuss the influence of angiogenesis and inflammation pathways on vascular permeability in VSs and SGCTs at the phenotypic level as well as their possible genetic and molecular determinants. Part I described the historical perspectives and clinical aspects of the relationship between vascular permeability, abnormal CSF protein levels, clotting of the CSF, and communicating hydrocephalus. Part II hereafter describes the different cellular and molecular pathways involved in angiogenesis and inflammation observed in both tumors and explores the existing metabolic overlap between inflammation and coagulation. Interestingly, while increased angiogenesis can be observed in both tumors, inflammatory processes seem significantly more prominent in SGCT. Both SGCT and VS are characterized by different subgroups of tumor-associated macrophages (TAMs): the pro-inflammatory M1 type is predominating in SGCTs, while the pro-angiogenetic M2 type is predominating in VSs. We suggest that a lack of NF2 protein in VS and a lack of TSC1/TSC2 proteins in SGCT significantly influence this fundamental difference between the two tumor types by changing the dominant TAM type. Since inflammatory reactions and coagulation processes are tightly connected, the pro-inflammatory state of SGCT may also explain the associated tendency for CSF clotting. The underlying cellular and molecular differences observed can potentially serve as an access point for direct therapeutic interventions for tumors that are specific to certain phacomatoses or others that also carry such genetic changes.     

Vascular hyperpermeability as a hallmark of phacomatoses: is the etiology angiogenesis comparable with mechanisms seen in inflammatory pathways? Part I: historical observations and clinical perspectives on the etiology of increased CSF protein levels,CSF clotting,and communicating hydrocephalus: a comprehensive review

Phacomatoses are a special group of familial hamartomatous syndromes with unique neuro-cutaneous manifestations as well as disease characteristic tumors. Neurofibromatosis 2 (NF2) and tuberous sclerosis complex (TSC) are representatives of this family. Vestibular schwannoma (VS) and subependymal giant cell tumor (SGCT) are two of the most common intracranial tumors associated with NF2 and TSC, respectively. These tumors can present with obstructive hydrocephalus due to their location adjacent to or in the ventricles. However, both tumors are also known to have a unique association with an elevated protein concentration in the cerebrospinal fluid (CSF), sometimes in association with non-obstructive (communicating) hydrocephalus (HCP), the causality of which has been unclear. Furthermore, SGCTs have repeatedly been shown to have a predisposition for CSF clotting, causing debilitating obstructions and recurrent malfunctions in shunted patients. However, the exact relation between high protein levels and spontaneous clotting of the CSF is not clear, nor is the mechanism understood by which CSF may clot in SGCTs. Elevated protein levels in the CSF are thought to be caused by increased vascular permeability and dysregulation of the blood–brain barrier. The two presumed underlying pathophysiologic mechanisms for that, in the context of tumorigenesis, are angiogenesis and inflammation. Both mechanisms are correlated to the Pi3K/Akt/mTOR pathway which is a major tumorigenesis pathway in nearly all phacomatoses. In this review, we discuss the influence of angiogenesis and inflammation on vascular permeability in VSs and SGCTs at the phenotypic level as well as their possible genetic and molecular determinants. Part I describes the historical perspectives and clinical aspects of the relationship between vascular permeability, abnormal CSF protein levels, clotting of the CSF, and communicating HCP. Part II describes different cellular and molecular pathways involved in angiogenesis and inflammation in these two tumors and the correlation between inflammation and coagulation. Interestingly, while increased angiogenesis can be observed in both VS and SGCT, inflammatory processes seem more prominent in SGCT. Both pathologies are characterized by different subgroups of tumor-associated macrophages (TAM): the pro-inflammatory, M1 type is predominating in SGCTs while pro-angiogenetic, M2 type is predominating in VSs. We suggest that lack of NF2 protein in VS and lack of TSC1/2 proteins in SGCT determine this fundamental difference between the two tumor types, by defining the predominant TAM type. Since inflammatory reactions and coagulation processes are tightly connected, a “pro-inflammatory state” of SGCT can be used to explain the observed associated enhanced CSF clotting process. These distinct cellular and molecular differences may have direct therapeutic implications on tumors that are unique to certain phacomatoses or those with similar genetics.     

Acquired glomerulocystic kidney disease following hemolytic uremic syndrome

Glomerulocystic kidney disease (GCKD) is a rare congenital condition that is usually reported in infants and young children. Only five cases of acquired GCKD after an acquired renal disease have been reported. Among these, two patients have developed cystic glomerular lesions following hemolytic uremic syndrome (HUS). We report a third case in a 2-year-old patient with this association. Common features between these three cases include atypical HUS, development of GCKD after prolonged peritoneal dialysis treatment, severe hypertension, and normal-sized kidneys without development of macroscopic cysts. Pathology findings in our patient include heavy expression of epidermal growth factor receptor in proximal tubules and evidence of obstruction of the glomerular outflow. We speculate that cystic dilatation of the Bowman’s capsule may be secondary to ischemic lesions leading to proximal tubular obstruction. Received: 6 October 2000 / Revised: 1 February 2001 / Accepted: 13 February 2001     

Parental hypertension and 24 h-blood pressure in children prior to diabetic nephropathy

In a search for predictors of nephropathy development, albumin excretion rate (AER), ambulatory blood pressure, and parental hypertension were assessed in 40 type 1 diabetic patients and 27 normal siblings (age<18 years) during a 2-year follow-up period. A double-antibody kit and an automated device were used for measuring 24-h AER and ambulatory blood pressure monitoring (ABPM), respectively. Patients had higher 24-h and daytime diastolic blood pressure (DBP), diastolic load, and daytime heart rate than siblings. Patients with hypertensive parents had higher 24-h DBP and diastolic load than patients with normotensive parents and all siblings. Non-dipping was more frequent in children with hypertensive parents (P<0.05). Both diabetes (P<0.001) and parental hypertension (P<0.05) had independent effects on longitudinal AER (average AER during follow-up). Patients with intermittent or persistent microalbuminuria showed a trend towards higher diastolic load (P<0.05); the latter group had higher 24-h DBP (P<0.01). Longitudinal AER correlated with 24-h DBP (P<0.01) and maternal mean blood pressure (P<0.05). Since changes in blood pressure preceded persistent microalbuminuria, ABPM might help to identify diabetic children prone to nephropathy. Received: 18 June 2001 / Revised: 1 October 2001 / Accepted: 4 October 2001     

Premature acute myocardial infarction in a child with nephrotic syndrome

We report a case of acute myocardial infarction in a nephrotic child. A 7-year-old boy with a 4-year history of steroid-unresponsive nephrotic syndrome due to mesangial proliferation disease presented with acute vomiting and chest pain. An electrocardiogram showed ST elevation and pathological Q waves in leads consistent with anterior and septal myocardial infarction. Subsequent cardiac catheterization showed no evidence of atherosclerotic coronary artery disease, and thrombotic occlusion of the anterior descending coronary artery was the likely cause of the event. Myocardial scintigraphy showed extensive myocardial damage. The child had no long history of extreme hypercholesterolemia or hypertriglyceridemia. The case suggests that children with long-lasting nephrotic syndrome may be at increased risk for ischemic cardiovascular events, due to hyperlipidemia as well as a hypercoagulability state. The literature is reviewed regarding the relationship between nephrotic syndrome and the incidence of ischemic heart disease. Received: 2 May 2001 / Revised: 31 October 2001 / Accepted: 18 November 2001     

Lithium-induced nephrotic syndrome in a young pediatric patient

Lithium-induced nephrotic syndrome is a rare complication of lithium therapy and is even rarer in children. Most reported cases have been secondary to minimal change disease, which reverses within 1–4 weeks on discontinuation of lithium therapy. However, focal glomerulosclerosis (FSGS) has occasionally been reported and is not always reversible with discontinuation of lithium. We report an 11-year-old child with lithium-induced FSGS nephrotic syndrome who went into full remission after lithium was discontinued. Received: 11 June 2001 / Revised: 9 October 2001 / Accepted: 9 October 2001     

Yield of renal arteriography in the evaluation of pediatric hypertension

The prevalence of renovascular disease is estimated to be 3%–5% in pediatric patients with hypertension. The utility of non-invasive imaging tests has not been evaluated in children, and renal arteriography remains the diagnostic test of choice. However, there are no established guidelines for the application of this test and information is not available about the likelihood of detecting an abnormality if an arteriogram is performed in children with hypertension. Therefore, we reviewed the yield of renal arteriography in pediatric patients if the test was performed based on the following two criteria: (1) severe hypertension exceeding the 99th percentile for age and sex or (2) failure to control high blood pressure with one antihypertensive drug. During the period 1983–1998, 28 children (mean age 11.7 years) who satisfied one of the above criteria underwent renal arteriography to investigate hypertension. None of the patients were renal transplant recipients. The average duration of hypertension was 11 months and the peak blood pressure was 168/107 mmHg. The renal arteriogram was abnormal in 12 patients (43%). Unilateral renal artery stenosis was the most-common abnormality. When the patients were divided into two groups – those with an abnormal or normal test result – they did not differ in age, sex, or racial distribution. The peak systolic blood pressure was higher in children with an abnormal renal arteriogram (P<0.05). Among those undergoing the arteriogram on the basis of the first criterion, i.e., severe hypertension, 11 of 23 (48%) studies were abnormal. Five children had an arteriogram based on the second criterion – failure to control the blood pressure with one medication – and in 1 patient (20%) the test was abnormal. We conclude that the prevalence of renovascular disease in a population of hypertensive children subjected to renal arteriography is around 40%. Two clinical criteria – namely severe hypertension or failure to control hypertension effectively with one drug – are useful to guide the application of renal arteriography in children with hypertension. Received: 12 August 1999 / Revised: 24 November 1999 / Accepted: 28 November 1999     

Increased apoptosis of peripheral blood lymphocytes in children with nephrotic syndrome

Nephrotic syndrome is accompanied by and probably related to abnormal T-lymphocyte function. Decreased stimulation of survival factors and increased levels of ”dead signals” may lead to the malfunction of many cells, including lymphocytes. In our study, we investigated the process of apoptosis within T cells in children with a first attack of nephrotic syndrome (NS). We found that the number of apoptotic T cells is greater in these patients than in both children in remission from NS and in controls. The percentage of annexin-V-fluorescein isothiocyanate (FITC)-positive CD3+ cells was 27.30± 12.13% in children with a first attack of NS, 19.22± 15.16% (P=0.006) in children in remission and 16.20± 6.13% (P=0.004) in controls. The percentage of annexin-V-FITC-positive CD3+CD4+ cells was 7.35±7.72% in children with a first attack of NS, 3.80±3.75% (P=0.0001) in children in remission and 3.82±2.01% (P=0.0002) in controls. We conclude that abnormal number and function of T lymphocytes found in NS patients may be related to an increased apoptotic rate of circulating lymphocytes. Received: 30 May 2001 / Revised: 11 October 2001 / Accepted: 13 October 2001     

Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case and review

Thrombotic thrombocytopenic purpura (TTP) is rare in children with systemic lupus erythematosus (SLE). We report a 15-year-old female who simultaneously presented with TTP and SLE. Kidney biopsy showed membranous nephropathy. Her condition improved with plasmapheresis, intravenous cyclophosphamide, and prednisone pulse therapy. We also reviewed the literature for this association in pediatric patients comparing presenting sequence and renal pathology with cases documented in the adult literature. Received: 30 October 2000 / Revised: 21 February 2001 / Accepted: 26 March 2001     

睾丸特异性新基因TSC23在小鼠和人睾丸组织中的表达分析

目的筛选与精子发生相关的睾丸特异性新基因，并探讨其在精子发生过程中所起的作用。方法将不同发育阶段的小鼠睾丸组织cDNA探针与Affymetrix全基因组芯片进行杂交，通过杂交信号的比较，筛选出差异表达的基因。用生物学信息软件对该基因进行生物学信息分析。RT-PCR分析该基因在小鼠不同发育阶段睾丸、小鼠不同组织及人不同组织中的表达。结果通过4、9、18、35、54d和6月龄小鼠睾丸的芯片信号比较筛选出一个差异表达基因（GenBank登录号：AK016041），全长有803bp，含有606bp的完整ORF，编码一个有201氨基酸、分子量为22．686kDa的蛋白质，我们将其命名为TSC23。亚细胞定位预测显示TSC23基因可能在细胞核中表达。SMART功能域分析表明氨基酸序列1-18区域为信号肽功能域，36-58区域为穿膜功能域。TSC23蛋白在人的同源基因GenBank登录号为XM-371248，在201个氨基酸区域内有75％的同源性。RT-PCR分析表明TSC23基因特异性表达于人和小鼠睾丸组织中，且只在38d和6月龄小鼠睾丸中表达。结论TSC23为人和小鼠睾丸特异性表达基因，只在38d和6月龄小鼠睾丸中表达，提示其可能在精子发生中起着重要作用。     

Arterial hypertension following renal transplantation in children—a short-term study

Systemic arterial hypertension is a common complication among transplanted patients. The objective of this study was to investigate the risk factors for arterial hypertension after kidney transplantation in children. A retrospective study was carried out of 70 kidney transplants performed on patients under 18 years of age at the Hospital do Rim and Hipertensão, from January 1998 to June 2001. At the end of 6 months post transplant, the patients were classified into either normotensive (n=31) or hypertensive (n=39) groups. The following potential risk factors for arterial hypertension were studied: (1) hypertension before transplantation; (2) the glomerular filtration rate (GFR) at 1, 3, and 6 months post transplant; (3) acute rejection episodes; (4) cumulative dose of corticosteroids; (5) the presence of native kidneys; (6) symptomatic renal artery stenosis; (7) cold ischemia time greater than 24 h; (8) age and sex of the donor; (9) age of the recipient; (10) transplant type (living related or cadaveric donor); (11) the body mass index of recipients at the end of the follow-up period; and (12) delayed graft function. The two groups were comparable in terms of the etiology of renal insufficiency, age, gender, and immunosuppressive drugs. Among the risk factors studied, the sole factor showing a statistically significant association with arterial hypertension was the GFR at 3 and 6 months after transplantation. In the group of normotensive patients, GFRs were 92±29 and 83±20 ml/min per 1.73 m² at 3 and 6 months, respectively, whereas in the hypertensive patients, GFRs were 74±23 and 70±21 ml/min per 1.73 m² respectively. Hence, only the lower GFR can be considered a risk factor for hypertension in children within our sample. However, arterial hypertension might be a risk factor for the early onset of chronic allograft nephropathy; in this case, hypertension should be considered the cause of lower glomerular filtration. Our data do not permit us to distinguish between these two hypotheses. The known risk factors for hypertension following renal transplantation in adults were not confirmed in the present study. It remains unclear to us as to whether this means the etiology of hypertension differs in children, or if this is the result of a bias in patient selection.     

Systolic hypertension in children: benign or beware?

Systolic blood pressure (SBP) has become the major criterion for the diagnosis, staging, and treatment of hypertension in adults, based on the epidemiology and pathophysiology of adult hypertension, linkage between SBP levels and disease, and benefits of treatment of isolated SBP hypertension. Although children do not typically suffer overt hypertensive disease, an accumulation of data suggests that SBP elevation is as important a factor in the morbidity of hypertension in children as in adults. SBP hypertension is more common in children, whether examining an unselected sample of patients by routine screening or a selected sample of referred hypertensive patients. Mild-to-moderate BP elevation in children is associated with increased left ventricular mass (LVM), with SBP more closely linked to LV morphology than diastolic blood pressure (DBP). Furthermore, SBP is associated with increased LVM even in patients with SBP within the ”normal” range. Among hypertensive children, the reported prevalence of LVH ranges from 30% to 70%, and LV hypertrophy is more closely related to SBP than to DBP. These data suggest that treatment of hypertension should be directed at normalization of SBP, even when DBP is within the normal range. In addition, trials of anti-hypertensive medications in children should incorporate SBP hypertension into study inclusion criteria. Received: 28 September 2000 / Revised: 13 December 2000 / Accepted: 18 January 2001     

Thalamic stroke secondary to straight sinus thrombosis in a nephrotic child

A 7-year-old Chinese boy with steroid-resistant nephrotic syndrome developed thalamic stroke secondary to straight sinus thrombosis. He was hospitalized due to status epilepticus and coma. The child recovered after treatment by low-molecular-weight heparin (LMWH) and warfarin. This case highlights the importance of magnetic resonance imaging with venography in the early diagnosis of cerebral sinus thrombosis (CST) in nephrotic children and the effectiveness of anticoagulation therapy in improving the neurological outcome. Received: 25 June 2001 / Revised: 6 September 2001 / Accepted: 12 October 2001     

False Aneurysm in the Palmar Segment of the Ulnar Artery: Report of a Case

A case demonstrating a false aneurysm in the palmar segment of the ulnar artery caused by a Fogarty's catheter, which had been inserted during a thrombectomy, is described. The diagnosis was suspected based on a clinical examination, and duplex ultrasonography and computed tomography (CT) confirmed an aneurysm in the palmar segment of the ulnar artery. The patient underwent a successful aneurysmectomy with end-to-end reanastomosis. Received: October 29, 2001 / Accepted: May 7, 2002 Reprint requests to: Y. ünlü, Atatürk Mah. Universite Loj, 38/8, Erzurum, Turkey     

Etiology of sustained hypertension in children in the Southwestern United States

We reviewed the records of 132 children with persistent hypertension who were evaluated by our pediatric nephrology services between 1987 and 1991. Eightynine (67%) of these children were found to have renal or renovascular disease, 30 (23%) had primary hypertension and 13 (10%) had a non-renal cause for their hypertension. Glomerulonephritis (n=37) and reflux nephropathy (n=26) were the most frequent renal disorders identified. Renal artery thrombosis was the most common cause of hypertension in the neonatal period (in 6 of 12 neonates, 50%) whereas cystic kidney disease was the most common cause of hypertension in the 1st year of life (in 9 of 30 infants, 30%). The prevalence of primary hypertension increased with age; this diagnosis was made in 16 of 46 (35%) hypertensive patients between 12 and 18 years of age and, more surprisingly, in 8 of 27 (30%) children between 7 and 11 years of age. These data confirm that secondary hypertension is the most common cause of hypertension in children but suggest that primary hypertension is more prevalent than previously recognized in patients between 7 and 18 years of age.     

Outcome in African-American children of neuropsychiatric lupus and lupus nephritis

The present study reviews the course of lupus nephritis (LN) with the added complication of neuropsychiatric systemic lupus erythematosus (NPSLE) in a predominantly African-American population in order to identify the risk factors accounting for the increased morbidity and mortality in African-American children. Previous studies, including those at our center, have demonstrated the poor prognosis for African-American children with LN. A possible factor is the involvement of the central nervous system (CNS), resulting in a heightened risk of morbidity, although to date there are no reports suggesting an association between NPSLE and patient and renal survival in children with lupus nephritis. To this end, we retrospectively analyzed charts of 72 children with lupus nephritis seen at our center from 1965 to 1999. These 72 patients formed two groups, with group 1 consisting of patients with lupus nephritis and NP manifestations and group 2 only lupus nephritis. We then examined various demographic factors such as age, sex and race along with the histopathologic class of lupus nephritis, occurrence of hypertension, incidence of end stage renal disease (ESRD), time to ESRD and mortality in both groups with the aid of Fisher’s exact t-test and the chi-square test. Briefly, the results revealed significantly higher class III or IV histopathologic lesions on biopsy, incidence of hypertension, progression to ESRD and mortality in children with NPSLE and LN (group 1) compared to LN alone (group 2) in spite of aggressive immunosuppressive therapy. In conclusion, we report that NPSLE with LN is associated with an increased rate of ESRD and mortality in our predominantly African-American children. Received: 26 March 2001 / Revised: 13 August 2001 / Accepted: 13 August 2001     

Severe hypertensive sequelae in a child with Seckel syndrome (bird-like dwarfism)

 We report a 19-year-old male with Seckel syndrome (bird-like dwarfism) who presents with malignant hypertension associated with hypertensive nephrosclerosis, dilated cardiomyopathy, and a ruptured cerebral artery aneurysm. Although end-organ injury due to chronic hypertension occurs frequently in adults, no previous reports of renal insufficiency due to hypertension exist in children or adolescents. We speculate that this patient may have been particularly prone to hypertensive end-organ injury due to his extreme short stature. Received: 6 May 1998 / Revised: 7 August 1998 / Accepted: 8 August 1998