[Placental angiogenic factors. Essentials and clinical significance in preeclampsia].
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Angiogenic Proteins↗
Biomedical subjects
D Dimitrakov
Publications and source records attributed to D Dimitrakov.
[Lymphocyte populations and subpopulations in peripheral blood of pregnant women with pre-eclampsia].
AIM: To investigate the changes of lymphocyte populations and subpopulations in peripheral blood of pregnant women suffering preeclampsia. MATERIAL AND METHODS: By means of flowcytometry the following lymphocyte populations and subpopulations were determined in peripheral blood of 37 pregnant women, of whom 12 had preeclampsia and 25 had normal pregnancy pespectively: Total lymphocyte count CD19+ (B-lymphocytes), CD2+ (Total T-lymphocytes), CD3+ (Immunocompetent T-lymphocytes) CD3+CD4+ (T-helpers), CD3+CD8+ (Suppressor-cytoxic T-lymphocytes), CD4+/CD8+ ratio, Lymphocyte subpopulations with predominant killer activity: CD8-CD56+, CD8+CD56+ and activated immunocompetent T-lymphocytes (CD3+HLADR+). RESULTS: In patients with preeclampsia a T-helper increase and relative T-suppressor cytotoxic decrease was found. A significant increase of activated immunocompetent T-lymphocyte was found, compared to the total increase of immunocompetent T cell. No significant difference between cytotoxic cell with MHC unrestrained function (CD8-CD56+) and cell with MHC restrained cytotoxic function (CD8+CD56+) was found. CONCLUSIONS: In pregnant women with preeclampsia the main lymphocyte populations and the immunocompetent T-lymphocytes are increased. The raised level of T-lymphocytes is found as a result of the substantial quantitative changes of T-helper cells an increase of CD4+/CD8+ ratio is prominent, which is a proof of the activated immune potential in pregnant women with preeclampsia with the dominant influence of T-helper subpopulations.
Antigens, CD↗
Angiotensin-converting enzyme activity and the ACE Alu polymorphism in autosomal dominant polycystic kidney disease.
BACKGROUND: Previous studies concerning Alu I/D polymorphism in the ACE gene and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual and ethnic differences in the proportion of variance in ACE activity explained by the I/D genotype may have confounded these studies. This investigation examines the association between ADPKD severity and ACE in terms of plasma enzyme activity and I/D genotypes in individuals from three different countries. METHODS: Blood samples were collected from 307 ADPKD patients (116 Australian, 124 Bulgarian and 67 Polish) for determination of ACE activity levels and I/D genotypes. Chronic renal failure (CRF) was present in 117 patients and end-stage renal failure (ESRF) in 68 patients. RESULTS: ACE activity was related to the I/D genotype, showing a dosage effect of the D allele (P=0.006). The proportion of variance due to the Alu polymorphism was 14%. No difference in ACE activity and I/D genotype distribution was found between patients with CRF versus normal renal function (P=0.494; P=0.576) or between those with ESRF versus those without ESRF (P=0.872; P=0.825). No effect of the I/D genotype on age at development and progression to renal failure (CRF; ESRF) was detected in the overall group, and in subgroups based on ethnic origin, linkage status and sex. CONCLUSION: ACE is not likely to play a role as a determinant of ADPKD phenotype severity.
Adolescent↗
Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene in 41 Bulgarian and Australian kindreds reveals a prevalence of protein truncating mutations.
Screening for disease-causing mutations in the unique region of the polycystic kidney disease 1 (PKD1) gene was performed in 41 unrelated individuals with autosomal dominant polycystic kidney disease. Exons 34-41 and 43-46 were assayed using PCR amplification and SSCP analysis followed by direct sequencing of amplicons presenting variant SSCP patterns. We have identified seven disease-causing mutations of which five are novel [c.10634-10656del; c.11587delG; IVS37-10C>A; c.11669-11674del; c.13069-13070ins39] and two have been reported previously [Q4010X; Q4041X]. Defects in this part of the gene thus account for 17% of our group of patients. Five of the seven sequence alterations detected are protein-truncating which is in agreement with mutation screening data for this part of the gene by other groups. The two other mutations are in-frame deletions or insertions which could destroy important functional properties of polycystin 1. These findings suggest that the first step toward cyst formation in PKD1 patients is the loss of one functional copy of polycystin 1, which indirectly supports the "two-hit" model of cystogenesis where a second somatic mutation inactivating the normal allele is necessary to occur for development of the disease condition.
3' Untranslated Regions↗
Screening for mutations in the peripheral myelin genes PMP22, MPZ and Cx32 (GJB1) in russian charcot-marie-tooth neuropathy patients; irina V. Mersiyanova, sookhrat M. Ismailov, alexandr V. Polyakov, elena L. Dadali, valeriy P. Fedotov, eva nelis, ann Lofgren, vincent timmerman, christine van broeckhoven, and oleg V. Evgrafov (Article was originally published in human mutation 15:340-347, 2000)
The authors wish to correct a mistake which occurred in the reporting of one of the mutations. The mutation in Cx32 Met34Lys is wrongly described as 100A>G. The correct description of the mutation should be 101T>A (Met34Lys).
Journal Article↗
Location of mutations within the PKD2 gene influences clinical outcome.
BACKGROUND: Since the cloning of the gene for autosomal dominant polycystic kidney disease type 2 (PKD2), approximately 40 different mutations of that gene have been reported to be associated with the disease. The relationship between the PKD2 genotype and phenotype, however, remains unclear. METHODS: Detailed clinical information was collected for PKD2 families in which the underlying mutation had been identified. Logistic regression analysis was employed to assess the influence of age and sex on hypertension, hematuria, renal calculi, and urinary tract infections, and a clinical phenotype score was computed. Patients were then grouped according to the relative location of their mutation within the cDNA sequence, and differences in the mean phenotypic score between groups were tested for statistical significance by means of a multiple pairwise t-test. RESULTS: While phenotypic scores for each mutational group revealed a considerable degree of intragroup variability, the variability in phenotypic scores was significantly higher between mutational groups than within groups. A group-wise comparison of the mean phenotypic scores confirmed the observation of significant nonlinear variation in disease severity, with high- and low-scoring mutational groups interspersed along the gene sequence. CONCLUSION: The identification of groups of mutations in the PKD2 gene, which differ significantly with respect to clinical outcome, is to our knowledge the first description of a genotype/phenotype correlation in autosomal dominant polycystic kidney disease. It also provides evidence against complete loss of function of the mutant PKD2 gene product.
Analysis of Variance↗
Frequency and clinical characteristics of mycoplasma urinary tract infections in the early post-transplantation period in renal allograft patients.
Using a highly sensitive and specific polymerase chain reaction (PCR) protocol, we studied 36 renal allograft recipients and 30 healthy controls. Midstream urine samples were analyzed using routine microbiological methods and the Mycoplasma IST (BioMerieux, France). Mycoplasma infections of the upper urinary tract were found in 9 patients. In three of them E.coli and Proteus were also present. We discuss the clinical characteristics of mycoplasma infections in the early post-transplantation period and its possible implications for graft rejection.
Adult↗
A case of Chlamydia trachomatis infection in a renal allograft patient.
We describe a renal allograft patient with a Chlamydia trachomatis infection. A 43 year-old man was diagnosed with end-stage renal disease in 1985 which necessitated the transplantation of a cadaver kidney in 1986. The kidney was rejected two years later. A second transplantation was performed in 1991. At the beginning of 1998 symptoms and signs of chronic renal failure and dysuria set in. Routine microbiological studies were negative. Cell culture on McCoy cell line was positive for an active infection with C. trachomatis--initially 3+, then 2+, 1+ and negative following treatment. The patient was positive on the AMPLICOR CT/NG test (Roche Diagnostic Systems, Branchburg, USA) twice with OD values OVER--above 2 at 450 nm wavelength measured on an ELISA reader. The patient received treatment with azithromycin and doxycycline for 10 days following which the serum creatinine levels fell and the creatinine clearance values improved. Dynamic microbiological follow-up showed disappearance of C. trachomatis as evidenced by the negative PCR test. We conclude that the deterioration of renal function in our patient is complex but the infection with C. trachomatis is part of the complex of the underlying chronic renal failure and immunosuppressive treatment.
Adult↗
Dynamic follow-up of the intact parathormone levels in hemodialysis patients treated with Rocaltrol and calcium.
UNLABELLED: The object of the present study was to follow prospectively the serum levels of intact parathormone (PTH) of hemodialysis patients and the subsequent changes following the oral administration of 1.25(OH)D3 and calcium. METHODS: We studied 30 chronic renal failure hemodialysis patients--16 men and 14 women, aged 20-70 years. Twenty-one of them were on hemodialysis with duration of up to 5 years (Group 1) and nine--up to 10 years (Group 2). All patients received oral supplementation therapy with 1.0 elemental calcium and Rocaltrol (Roche) 0.25 microgram/day. We measured the serum calcium, ionized calcium, serum phosphorus, alkaline phosphatase and the intact serum PTH levels in intervals of 12 months. RESULTS: Patients with duration of dialysis of up to 5 years had a significantly lower baseline PTH level of 392.5 +/- 94.7 pg/ml versus 896.4 +/- 160.7 pg/ml for those from the second group (P < 0.01). The intact PTH levels showed a tendency towards decrease--at the end of the study they were as follows: 372.02 +/- 76.9 for group 1 versus a significant increase for those from group 2--serum PTH levels of 1793.65 +/- 290.3 (P < 0.02). The differences in alkaline phosphatase and serum phosphorus levels at the end of the study period failed to reach statistical significance. Serum calcium levels were increased in both groups following the initiation of treatment but the difference was statistically significant only for group 2. A significant positive correlation was observed between the duration of hemodialysis treatment and the intact serum PTH levels. CONCLUSIONS: 1. Long-term low-dose conventional calcitriol therapy in combination with calcium supplementation could slow the progression of secondary hyperparathyroidism in some hemodialysis patients. 2. Low-dose therapy with active vitamin D-metabolites is effective only in hemodialysis patients with baseline serum PTH levels below 500 pg/ml and without pronounced hyperphosphatemia.
Adult↗
PCR studies on the presence of Chlamydia trachomatis in the upper urinary tract of patients with obstructive pyelonephritis.
Chlamydia trachomatis infections are among the most common sexually transmitted diseases in the world and it is only logical to hypothesize that it alone or in association with mycoplasmas can participate in the initiation and persistence of upper urinary tract infections. Having in mind the inconclusive evidence regarding the role of C. trachomatis in upper urinary tract infections we decided to study the presence of C. trachomatis in the upper urinary tract of patients with obstructive pyelonephritis using the polymerase chain reaction. We studied 20 patients (12 female and 8 male, aged 20-60 years) with symptoms and signs of acute pyelonephritis in accordance with Kunin's criteria (1997). Samples were taken during surgery of the upper urinary tract by aspirating urine from the renal pelvis or the ureter above the level of the obstruction and analyzed for the presence of bacterial pathogens using routine microbiological techniques and employing the "AMPLICOR CT/NG" test (Roche Diagnostic Systems, Branchburg, NJ, USA) for the presence of C. trachomatis. Chlamydia trachomatis was found in the aspirated urine of 5 patients (25%). In 3 of the patients the microbiological tests of the aspirated urine did not establish any other microbial agent. In the other two Escherichia coli and Proteus mirabilis were cultured. The analysis of the clinical and laboratory findings in the patients with Chlamydia trachomatis infection alone and those with an associated bacterial pathogen failed to reach statistical significance. Following the operation all of the patients received treatment with Ofloxacin 200 mg bid for 7 days with a favorable clinical and laboratory outcome. In our opinion, the AMPLICOR CT/NG test is a sensitive and specific method for diagnosing low-number Chlamydia trachomatis infections of the upper urinary tract in patients with obstructive pyelonephritis. Chlamydia trachomatis should be considered as a possible etiologic agent in acute pyelonephritis and the therapeutic regimen in such patients should be targeted at its possible underlying presence.
Adult↗
On the disturbances in carbohydrate metabolism in pre-dialysis patients with chronic renal failure.
UNLABELLED: We describe some of the aspects of impaired carbohydrate metabolism in predialysis uremic patients. METHODS: A total of seventy-five nondiabetic patients with chronic renal failure (CRF) were enrolled in the present study. The level of glycosylated hemoglobin was measured in 51 patients using kits from Merck and an oral glucose challenge test was performed in 20 according to a standard protocol. The levels of immunoreactive insulin and growth hormone (GH) were measured in all predialysis patients using original kits and an automatic minigamma counter (Abbott, USA). The results were compared with those from 30 healthy controls. RESULTS: In patients with first degree CRF the level of glycosylated hemoglobin was 5.9 +/- 05%. In patients with second and third degree CRF there was a trend towards higher glycosylated hemoglobin levels--6.3 +/- 0.6% (P > 0.05; u = 1.1) as compared with the controls--5.5 +/- 0.4%. The analysis of the results from the oral glucose challenge test revealed impaired glucose tolerance in 12 predialysis patients with CRF with blood glucose levels of 9.1 +/- 1.6 mmol/l at the second hour following the ingestion of glucose. Nine of those had second or third degree CRF. The baseline levels of plasma immunoreactive insulin showed a tendency towards increase in the patients with uremia as compared with the controls (7.2 +/- 1.1 IU/ml versus 6.4 +/- 0.7 IU/ml) whereas no significant difference was found at the 1st, 2nd or 3rd hour following the ingestion of glucose as compared with the healthy controls. Five of our patients had significantly elevated basal insulin levels. With regard to GH levels, we found similar baseline values in our study patients and the controls. At the 1st hour following the glucose challenge the GH values showed a tendency towards increase in the uremic patients--6.1 +/- 1.1 ng/ml. In 4 of our study patients we found significantly elevated GH levels at the 1st hour following the ingestion of glucose (6.6 +/- 0.7 ng/ml). CONCLUSIONS: 1. No significant disturbances in carbohydrate metabolism were found in patients with mild (initial) CRF. 2. In patients with moderate and advanced CRF we found changes consistent with impaired carbohydrate metabolism and a tendency towards an increase in the basal immunoreactive insulin levels. 3. Growth hormone levels showed a different pattern of change in predialysis patients and those changes cannot be explained by the changes in carbohydrate metabolism.
Carbohydrate Metabolism↗
A case of primary Sjögren's syndrome in combination with chronic mesangiocapillary glomerulonephritis and interstitial nephritis.
UNLABELLED: The authors present an extremely rare case of combination of primary Sjögren's syndrome and chronic glomerulonephritis, which was subsequently found to be mesangiocapillary on pathohistologic examination. METHODS: This case of mesangiocapillary glomerulonephritis in combination with interstitial nephritis is characterized in terms of the clinical, laboratory, immunologic and instrumental methods for diagnosis. Percutaneous kidney biopsy was performed and the characteristic findings on light microscopy were recorded. RESULTS: The therapeutic regimen consisting of pulse therapy with Immunovenin-intact and cyclophosphamide resulted in long-term clinical and laboratory remisson of the glomerulopathy and positively influenced the remaining syndromes. CONCLUSION: Pulse therapy with these drugs is an alternative to conventional pathogenetic therapy; it can also be the therapeutic modality of choice in cases similar to the one described here having in mind the long-term therapeutic remission.
Chronic Disease↗
Our experience in the combined pathogenetic treatment of chronic glomerulonephritis.
UNLABELLED: The most common combined pathogenetic treatment regimens for the treatment of chronic glomerulonephritis are the object of the present study. It is not quite uncommon in everyday clinical practice for the physician to encounter patients with similar pathohistologic patterns who respond differently to a standard therapeutic schedule. METHODS: Having in mind the complexity of the problem we analyzed our ten-year experience with the combined pathogenetic treatment of 150 patients, aged 17 to 52, with histologically proven chronic glomerulonephritis. The diagnosis was made on the basis of light microscopy, immunofluorescent and, where available, electron microscopy studies of kidney biopsies using clinical and laboratory criteria. In most cases the combined pathogenetic treatment included standard dosage regimens consisting of corticosteroids--Prednisolone in a dose of 1.0-1.5 mg/kg, cytotoxic agents--Cyclophosphamide 1.0-1.5 mg/kg, anticoagulants--heparin (Calciparin) given for one month and antiplatelet drugs--Dipyridamole 300 mg/day. When the preceding regimen was unsuccessful the patients were given pulse therapy with Methylprednisolone 10-15 mg/kg on three successive days or Cyclophosphamide 10 mg/kg in a single dose. Those who failed to respond to the standard pathogenetic and pulse therapy were treated with Cyclosporin (Sandimmun-Sandoz) in a daily dose of 2-5 mg/kg. Complete remission occurred in forty-two patients (63.6%) with mesangial proliferative glomerulonephritis and 18 patients (60%) with membranous glomerulonephritis. The remaining patients were non-responders. RESULTS: The highest percentage of patients with complete remission was observed among those with minimal-change glomerulonephritis--20 patients (95.2%) and the lowest--among those with mesangiocapillary glomerulonephritis--5 patients (27.7%), focal segmental glomerular sclerosis and hyalinosis and sclerosing glomerulonephritis--11.1% and 16.7%, respectively. CONCLUSIONS: The authors think that at present the combined pathogenetic treatment of chronic glomerulonephritis has no alternative and can slow the progression of the renal injury as well as influence favorably the short- and long-term prognosis of the patient with glomerulonephritis.
Adolescent↗
Cyclic adenosine monophosphate (cAMP) levels in predialysis patients with chronic renal failure.
We studied the changes in the urinary cAMP level in fifty-five predialysis patients (30 men and 25 women) with chronic renal failure (CRF). The excretion of cAMP in 20 patients with first-degree CRF (serum creatinine levels below 356.6 mmol/I) and 15 patients with second or third degree CRF (serum creatinine below 800 mmol/I) was compared with that of 20 age-matched controls using the original I-125 RIA (radioimmunoassay) kit of Incstar Corporation, USA. The urinary cAMP was within normal limits in first-degree CRF patients (mean +/- Sx = 2,617 +/- 268.2 nmol/l) whose serum calcium level was slightly decreased. When calculated per 100 ml of glomerular filtration rate, their urinary cAMP level was significantly elevated--101.17 +/- 0.39--as compared with that of the controls--2.5 +/- 0.2. The urinary cAMP excretion was significantly higher in second and third degree CRF patients--mean 3,755 +/- 435.2 nmol/l, p < 0.05. This increase correlated with hypocalcemia whereas the serum alkaline phosphatase levels remained normal. 20% of the patients with second or third degree CRF had normal urinary cAMP excretion. In our opinion, urinary cAMP levels can reliably be employed as a sensitive and specific indicator of the onset of mild secondary hyperparathyroidism in predialysis patients with CRF.
Adult↗
Acute renal failure--etiologic and therapeutic considerations. A five-year experience at a single institution.
In the present study we highlight the epidemiology, etiologic spectrum, and evaluation of ARF in adults. We then expand on the pathophysiologic mechanisms of renal failure and discuss the rationale for current therapeutic strategies in ARF patients. A total of 79 patients (45 male, female 34), aged 18-75 years (median age 51.2 +/- 17.7 years) with acute renal failure were studied in 5 years (January 1990 through October 1995). Emergency hemodialysis sessions following an acute anuric episode were instituted in 39 cases (49.3% of all patients). The median number of hemodialysis procedures per patient treated at our institution was 3.2 +/- 1.9. The total number of acute interstitial nephritis-associated ARF was 40. In 30 of them (75%) the acute renal insult included a combination of several therapeutic antimicrobial agents, in 2 cases (5%) ARF followed the administration of nonsteroidal anti-inflammatory drugs, in 1 (2.5%) it resulted from a combined therapeutic regimen and in the remaining 5 (12.5%) from the application of a single drug. Acute interstitial nephritis developed in 2 patients following a viral infection. In the hemodialysis-treated ARF group 12 patients (29.77%) had interstitial nephritis and 2 patients (5.13%) presented with renal impairment for an unspecified period of time preceding the development of overt ARF. In a subset of this group of patients, ARF occurred in 7 patients (17.95%) following an urologic intervention, in 8 patients (20.51%) as a consequence of thermal or mechanical trauma or intoxication and in 3 cases (7.69%) it resulted from fever of unknown origin. Three patients with postoperative peritonitis and 4 other (10.26%) with postoperative complications were encountered in our series. No cases of septic abortion-related or obstetric-related ARF were recorded. 92.3% of all hemodialysis-treated patients seen at our Institution had received a combination of antibiotics and only 2 patients had been pre-treated with a single antimicrobial agent. Our results underscore the strong tendency towards diversity in the etiologic spectrum of clinical entities causing ARF and the increase in the number of acute interstitial nephritis. These factors highlight the importance of precise dosing and administration of drugs, especially antibiotics, as well as the duration of antibiotic treatment.
Acute Kidney Injury↗
Comparative analysis of clinical manifestations of autosomal dominant polycystic kidney disease depending on linkage to chromosome 16.
The present study concerns 63 patients with autosomal polycystic kidney disease. In 35 patients the disease was linked to chromosome 16, and in the remaining 28 it was not linked to this chromosome. A comparative clinical analysis of the clinical manifestations of each of the forms was carried out using the objective criteria of age at onset of the initial clinical manifestations of ADPKD, age at onset of the hypertension syndrome, age at onset of the initial chronic renal failure and beginning of haemodialysis. The results show that the clinical manifestations of ADPKD in the patients with the unlinked from are milder and with a better prognosis.
Adult↗
Clinical electron microscopic correlations in patients with glomerulonephritis.
The purpose of the present study was to perform an electron microscopic investigation of patients with chronic glomerulonephritis and to find correlations between the type of glomerular disorder and the features of the clinical course of the disease. 26 patients--16 female and 10 male aged 17-62 years (mean age, 34.5 years) were investigated. All patients were clinically diagnosed as having chronic glomerulonephritis with a disease duration ranging from 3 months to 2 years. The main clinical and laboratory parameters studied were presence of edemas, hypertension, proteinuria, hyperlipidemia, haematuria and renal failure confirmed by the creatinine clearance. A puncture renal biopsy was performed by classical methods under ultrasound guidance using a Vim-Silverman needle. An electron microscope Philips CM-12 was used in the study. We found in all patients a significant correlation between the degree of proteinuria and the marked deformation and edema of the podocyte pedicles. In making the integral histological diagnosis of chronic glomerulonephritis it is necessary to determine more precisely the mesangial involvement and the changes in the membrane by means of an electron microscopic study. This will be conducive to a reduction in the number of mistakes in diagnosing some primary chronic glomerulonephrites.
Adolescent↗
Genetic heterogeneity of polycystic kidney disease in Bulgaria.
Linkage analysis was performed on 22 Bulgarian families with polycystic kidney disease (PKD) ascertained through the hemodialysis centers of two medical schools. A total of 128 affected and 59 unaffected individuals, and 54 spouses have been investigated using eight polymorphic markers linked to PKD1 and nine markers to PKD2. The results demonstrate locus heterogeneity with 0.67 as the maximum likelihood value of alpha, i.e., the proportion of families linked to PKD1. In five families, the results suggest linkage to PKD2 and observed recombinants place the gene between loci D4S1544 and D4S1542. In one family, two double recombinants for closely linked markers on chromosome 16 and on chromosome 4 give evidence for the lack of linkage to either PKD1 or PKD2, thus suggesting the involvement of a third locus. Analysis of clinical data in the PKD1 group versus the unlinked group shows no significant differences in the severity of the disease.
Adult↗