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Biomedical subjects

J M Middeldorp

Publications and source records attributed to J M Middeldorp.

At least 19 recordsLinked to original sources
PubMed2007

Fetoscopic laser surgery in 100 pregnancies with severe twin-to-twin transfusion syndrome in the Netherlands.

OBJECTIVE: In this prospective cohort study, we evaluated the initial results of fetoscopic laser surgery for severe second trimester twin-to-twin transfusion syndrome (TTTS) treated at our centre. METHOD: A total of 100 consecutive pregnancies with severe second trimester TTTS treated at our centre with selective fetoscopic laser coagulation of vascular anastomoses on the placental surface between August 2000 and November 2004 were included in the study. Perinatal survival was analysed in relation to Quintero stage. RESULTS: Median gestational age was 20 weeks at fetoscopy (range: 16-26) and 33 weeks at delivery (range: 18-40). Perinatal survival rate was 70% (139/200). The treatment resulted in at least one survivor at the age of 4 weeks in 81% of pregnancies. Perinatal survival was significantly higher when treatment was performed in the early Quintero stages (95% in stage 1, 76% in stage 2, 70% in stage 3, 50% in stage 4) (p = 0.02). CONCLUSION: Results of fetoscopic laser surgery for TTTS in our centre are similar to those in specialised centres in other countries. Diagnosis and treatment in the early Quintero stages resulted in significantly higher perinatal survival.

Female↗
PubMed2006

Assessment of feto-fetal transfusion flow through placental arterio-venous anastomoses in a unique case of twin-to-twin transfusion syndrome.

In vivo measurements of blood flow through arterio-venous anastomoses in monochorionic twin placentas have recently been attempted with Doppler ultrasound, but the accuracy is questionable. We present a case of twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. The ex-recipient subsequently became severely anaemic and was treated with an intrauterine blood transfusion at 29 weeks' gestation. After birth, a placental injection study identified residual unidirectional arterio-venous anastomoses from the ex-recipient to the ex-donor without arterio-venous anastomoses in the opposite direction. Prospective measurements of decreasing haemoglobin levels between the intrauterine transfusion and birth allowed us to assess the net blood flow through the anastomoses as 27.9mL/24h. This finding may also explain the inaccuracy of Doppler flow measurements, as such low flow velocities cannot possibly be detected with current Doppler techniques.

Adult↗
PubMed2006

Residual anastomoses after fetoscopic laser surgery in twin-to-twin transfusion syndrome: frequency, associated risks and outcome.

Fetoscopic laser coagulation of placental vascular anastomoses is considered to be the treatment of choice in severe twin-to-twin transfusion syndrome. The aim of fetoscopic laser surgery is to separate completely the inter-twin placental circulation. Incomplete laser coagulation may result in residual vascular anastomoses. The incidence and clinical implications of residual anastomoses in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery has not yet been studied. We examined all placentas treated with fetoscopic laser surgery and delivered at our center between June 2002 and December 2005 with vascular injection using colored dyes. Presence of residual anastomoses was studied in association with adverse outcome and inter-twin hemoglobin difference at birth. Adverse outcome was defined as fetal demise, neonatal death or severe cerebral injury. The relation between residual anastomoses and placental localization (anterior or posterior uterine wall) was evaluated. A total of 52 laser-treated placentas were studied. Residual anastomoses were detected in 33% (17/52) of placentas. Adverse outcome was similar in the groups with and without residual anastomoses, 18% (6/34) and 29% (20/70), respectively (p=0.23). Large inter-twin hemoglobin differences (>5g/dL) were found in 65% (11/17) of cases with residual anastomoses and 20% (7/35) of cases without residual anastomoses (p<0.01). Anterior placental localization was not associated with a more frequent presence of residual anastomoses. In conclusion, residual anastomoses at our institution are seen in one-third of monochorionic placentas treated with fetoscopic laser surgery. Although residual anastomoses in our study were not associated with adverse outcome, they were often associated with neonatal hematological complications.

Arteriovenous Anastomosis↗
PubMed2006

Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligo-polyhydramnios sequence.

Placental vascular anastomoses in monochorionic twins may lead to acute or chronic inter-twin transfusion. We report an uncommon form of chronic inter-twin transfusion, referred to as twin anemia-polycythemia sequence (TAPS), with severe anemia in one twin and polycythemia in the other, without the characteristically associated twin oligo-polyhydramnios sequence (TOPS) seen in the classical twin-to-twin transfusion syndrome (TTTS). The clinical course and placental characteristics of two pairs of monochorionic twins with TAPS born at, respectively, 33 and 34 weeks' gestation were reviewed. Serial fetal ultrasound examinations revealed no signs of TOPS. At birth, both donor twins were severely anemic requiring blood transfusion and both recipients were polycythemic, one requiring partial volume exchange transfusions. Inter-twin difference in reticulocyte counts was extremely high, suggesting a chronic form of inter-twin blood transfusion. Placental injection studies revealed a preponderance of very small (<1mm) arterio-venous anastomoses in one direction. In conclusion, chronic inter-twin transfusion may lead to an uncommon form of inter-twin transfusion, named TAPS, not associated with TOPS, resulting in severe fetal or neonatal hematological complications. We hypothesize that TAPS is mediated through minuscule unidirectional anastomoses. TAPS can be diagnosed antenatally with Doppler studies and postnatally by hemoglobin and reticulocyte measurements.

Adult↗
PubMed2006

Timely diagnosis of twin-to-twin transfusion syndrome in monochorionic twin pregnancies by biweekly sonography combined with patient instruction to report onset of symptoms.

OBJECTIVES: To assess the value of serial ultrasound examinations together with patient instructions to report the onset of symptoms in achieving timely detection of twin-to-twin transfusion syndrome (TTTS) in a cohort of monochorionic diamniotic twin pregnancies, and to evaluate sonographic TTTS predictors. METHODS: Timely detection of TTTS was defined as diagnosis before severe complications of TTTS occurred, such as preterm prelabor rupture of membranes, very preterm delivery (24-32 weeks of pregnancy), fetal hydrops, or intrauterine fetal death. During a 2-year period, a prospective series of 23 monochorionic twin pregnancies was monitored from the first trimester until delivery. At least every 2 weeks we performed ultrasound and Doppler measurements (nuchal translucency thickness, presence of membrane folding, estimated fetal weight, deepest vertical pocket, bladder filling, and Doppler waveforms of the umbilical artery, ductus venosus and umbilical vein). Measurements of TTTS cases were compared with those of non-TTTS cases matched for gestational age. Furthermore, patients were informed about the symptoms caused by TTTS, and instructed to consult us immediately in case of rapidly increasing abdominal size or premature contractions. RESULTS: In all four TTTS cases, the diagnosis was timely. At the time of diagnosis, one case was at Quintero Stage 1, two at Quintero Stage 2, and one at Quintero Stage 3. Two of the TTTS cases became apparent after the patients' feeling of rapidly increasing girth. The identification of TTTS predictors was successful with respect to one parameter: isolated polyhydramnios in one sac, without oligohydramnios in the other, preceded the ultimate diagnosis of TTTS in two of the four TTTS cases. All other ultrasound measurements of TTTS cases, prior to the diagnosis of TTTS, were within the range of measurements of non-TTTS cases. CONCLUSION: Biweekly ultrasound examinations, with special attention to the amniotic fluid compartments of both fetuses, combined with detailed patient instructions to report the onset of symptoms resulted in timely diagnosis of all TTTS cases and appears to be a safe program for monitoring monochorionic twin pregnancies.

Adult↗
PubMed2006

Amnioinfusion to facilitate external cephalic version after initial failure.

OBJECTIVE: To evaluate the effectiveness of antepartum transabdominal amnioinfusion to facilitate external cephalic version after initial failure. METHODS: Women with a structurally normal fetus in breech lie at term, with a failed external cephalic version and an amniotic fluid index (AFI) less than 15 cm, were asked to participate in our study. After tocolysis with indomethacin, a transabdominal amnioinfusion was performed with an 18G spinal needle. Lactated Ringers solution was infused until the AFI reached 15 cm, with a maximum of 1 L. External cephalic version was performed directly afterward. RESULTS: Seven women participated in the study. The gestational age of the women was between 36(+4) and 38(+3) weeks, and three women were primiparous. The AFI ranged from 4 cm to 13 cm. A median amount of 1,000 mL Ringers solution (range 700-1,000 mL) was infused per procedure. The repeat external cephalic versions after amnioinfusion were not successful in any of the patients. CONCLUSION: In our experience, amnioinfusion does not facilitate external cephalic version.

Adult↗
PubMed2006

Single-assay combination of Epstein-Barr Virus (EBV) EBNA1- and viral capsid antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G (IgG) and IgA antibody levels in sera from nasopharyngeal carcinoma patients: options for field screening.

Assessment of immunoglobulin A (IgA) antibody responses to various Epstein-Barr virus (EBV) antigen complexes, usually involving multiple serological assays, is important for the early diagnosis of nasopharyngeal carcinoma (NPC). Through combination of two synthetic peptides representing immunodominant epitopes of EBNA1 and viral capsid antigen (VCA)-p18 we developed a one-step sandwich enzyme-linked immunosorbent assay (ELISA) for the specific detection of EBV reactive IgG and IgA antibodies in NPC patients (EBV IgG/IgA ELISA). Sera were obtained from healthy donors (n = 367), non-NPC head and neck cancer patients (n = 43), and biopsy-proven NPC patients (n = 296) of Indonesian and Chinese origin. Higher values of optical density at 450 nm for EBV IgG were observed in NPC patients compared to the healthy EBV carriers, but the large overlap limits its use for NPC diagnosis. Using either EBNA1 or VCA-p18 peptides alone IgA ELISA correctly identified 88.5% and 79.8% of Indonesian NPC patients, with specificities of 80.1% and 70.9%, whereas combined single-well coating with both peptides yielded sensitivity and specificity values of 90.1 and 85.4%, respectively. The positive and negative predictive values (PPV and NPV, respectively) for the combined EBNA1 plus VCA EBV IgA ELISA were 78.7% and 93.9%, respectively. In the Indonesia panel, the level of EBV IgA reactivity was not associated with NPC tumor size, lymph node involvement, and metastasis stage, sex, and age group. In the China panel the sensitivity/specificity values were 86.2/92.0% (EBNA1 IgA) and 84.1/90.3% (VCA-p18 IgA) for single-peptide assays and 95.1/90.6% for the combined VCA plus EBNA1 IgA ELISA, with a PPV and an NPV for the combined EBV IgA ELISA of 95.6 and 89.3%, respectively. Virtually all NPC patients had abnormal anti-EBV IgG diversity patterns as determined by immunoblot analysis. On the other hand, healthy EBV carriers with positive EBV IgA ELISA result showed normal IgG diversity patterns. By using EBV IgG immunoblot diversity as confirmation assay for EBV IgA ELISA-positive samples, the sensitivity and specificity for NPC diagnosis increased to 98% and 99.2%, respectively, in the Indonesian NPC samples. The use of these combined methods for seroepidemiological screening studies is proposed.

Antigens, Viral↗
PubMed2005

Comparison of three different serological techniques for primary diagnosis and monitoring of nasopharyngeal carcinoma in two age groups from Tunisia.

Nasopharyngeal carcinoma (NPC) in Tunisia is characterized by its bimodal age distribution involving juvenile patients of 10-24 years and adult patients of 40-60 years. Three serological techniques were compared for primary diagnosis (N = 117) and post-treatment monitoring (N = 21) of NPC patients separated in two age groups. Immunofluorescence assay (IFA) was used as the "gold standard" for detection of IgG and IgA antibodies reactive with Epstein-Barr virus (EBV) early (EA) and viral capsid (VCA) antigens. Results were compared with ELISA measuring IgG and IgA antibody reactivity to defined EBNA1, EA, and VCA antigens. Immunoblot was used to reveal the molecular diversity underlying the anti-EBV IgG and IgA antibody responses. The results indicate that young NPC patients have significantly more restricted anti-EBV IgG and IgA antibody responses with aberrant IgG VCA/EA levels in 78% compared to 91.7% in elder patients. IgA VCA/EA was detected in 50% of young patients versus 89.4% for the elder group (P < 0.001). Immunoblot revealed a reduced overall diversity of EBV antigen recognition for both IgG and IgA in young patients. A good concordance was observed between ELISA and IFA for primary NPC diagnosis with 81-91% overall agreement. Even better agreement (95-100%) was found for antibody changes during follow-up monitoring, showing declining reactivity in patients in remission and increasing reactivity in patients with persistent disease or relapse. ELISA for IgA anti-VCA-p18 and immunoblot proved most sensitive for predicting tumor relapse. VCA-p18 IgA ELISA seems suitable for routine diagnosis and early detection of NPC complication.

Adolescent↗
PubMed2005

Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation.

OBJECTIVE: Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. METHODS: Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. RESULTS: Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). CONCLUSION: If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

ABO Blood-Group System↗
PubMed2004

Expression and analysis of the Epstein-Barr virus BARF1-encoded protein from a tetracycline-regulatable adenovirus system.

Epstein-Barr virus (EBV) has been associated with human cancers of lymphocytic or epithelial origin. Potential functions of the BARF1 early gene in EBV oncogenesis emerged from our observations showing expression of BARF1-encoded protein in nasopharyngeal carcinoma biopsies, and induction of either malignant transformation (in rodent fibroblast and human B cell lines) or immortalization (in monkey primary epithelial cells) following BARF1 transfection. We previously reported expression of the BARF1 product as a cytoplasm/membrane-associated protein from 293-tTA cells infected with a BARF1-recombinant adenovirus. Since constitutive expression of BARF1 from this heterologous system became inefficient, we developed a tetracycline-regulatable recombinant vector expressing BARF1 and green fluorescent protein from a dicistronic message. As here reported, stable and efficient expression of BARF1 from this vector in either permissive or non-permissive cell lines, allowed the first sequencing identification and further molecular characterization of BARF1-encoded protein.

Adenoviridae↗
PubMed2004

[The initial results of fetoscopic laser treatment for severe second trimester twin-to-twin transfusion syndrome in the Netherlands are comparable to international results].

OBJECTIVE: Evaluation of the initial results of selective fetoscopic laser coagulation of placental blood vessels for severe second-trimester twin-to-twin transfusion syndrome in the Netherlands. DESIGN: Prospective cohort study. METHOD: Between August 2000 and December 31, 2002, 49 patients were included with severe second-trimester twin-to-twin transfusion syndrome. Treatment took place in the Leiden University Medical Centre and consisted of selective fetoscopic laser coagulation of anastomoses along the vascular equator on the placental surface. Follow-up was complete until six weeks after delivery. RESULTS: Median gestational age was 20 weeks at fetoscopy and 34 weeks at birth. Perinatal survival rate was 65% (64/98). The treatment resulted in at least one surviving child in 80% of pregnancies. CONCLUSION: The results of fetoscopic laser treatment for severe second-trimester twin-to-twin transfusion syndrome in the Netherlands are similar to the recent results in specialised foreign centres.

Cohort Studies↗
PubMed2003

Genetic diversity: frameshift mechanisms alter coding of a gene (Epstein-Barr virus LF3 gene) that contains multiple 102-base-pair direct sequence repeats.

Frameshift mutations provide recognized mechanisms for changing the coding potential of an organism. Here, multiple frameshifts are identified in repetitive sequences within an Epstein-Barr virus unspliced early gene, LF3, which is associated with the viral replicative cycle and also transcriptionally expressed in many virally associated tumors. On the DNA strand encoding LF3, there are three open reading frames, only one of which contains an initiation codon. Most (>95%) of the gene consists of numerous (>20, varying with cell source) GC-rich copies of a 102-bp direct repeat (called IR 4) flanked by small unique sequences. LF3 may express a protein if its initiation and termination codons reside in the same reading frame, but this is not always the case. Frameshifting events, occurring in short runs of pyrimidines (mainly C residues) in the repeats, give rise to mutations which may provide a mechanism for escape of an LF3 function from host surveillance. Sequence studies link these frameshifts to DNA replication errors. Notably, the number of sites in LF3 at which such mutations can occur permits a very large amount of diversity in this gene. Our data also suggest a second degeneracy mechanism within the protein itself, which influences its stability and may reflect a host defense mechanism. LF3 thus provides a potentially important model for studying the quest for supremacy between a virus and its host.

Amino Acid Sequence↗
PubMed2002

Detection of late pp67-mRNA by NASBA in peripheral blood for the diagnosis of human cytomegalovirus disease in AIDS patients.

OBJECTIVE: To evaluate the value of late-pp67-mRNA nucleic acid sequence-based amplification (NASBA) in comparison to DNA-PCR, blood culture and pp65-antigenemia assay for the detection of human cytomegalovirus (HCMV) disease in HIV-infected patients. METHODS: The results of pp67-mRNA NASBA, DNA-PCR, culture and pp65-antigenemia assay were compared in 402 whole blood specimens of 98 HIV-infected patients with a low CD4 lymphocyte count who had not yet received highly active antiretroviral therapy (HAART). Thirty-seven samples were obtained from 30 patients with a diagnosis of HCMV disease and 365 samples from 68 patients without HCMV disease. RESULTS: The highest agreement of test results was observed between pp67-mRNA NASBA and quantitative pp65-antigenemia, with a threshold of nine antigen-positive cells/10(5) leukocytes (kappa-value 0.70, 95% CI=0.58-0.82). The sensitivity of pp67-mRNA NASBA for the diagnosis of HCMV disease (59.3%) was identical to that of the quantitative pp65-antigenemia assay, higher than that of the blood culture (48.2%) but lower than that of the DNA-PCR (77.8%). Pp67-mRNA NASBA (92.3%), quantitative pp65-antigenemia assay (92.3%) and blood culture (93.9%) were highly specific for the diagnosis of HCMV disease and as a result, had a higher positive predictive value (76.2, 76.2 and 76.5%, respectively) than the qualitative DNA-PCR (58.3%) and the qualitative pp65-antigenemia assay (47.6%). CONCLUSION: pp67-mRNA NASBA, an easy and rapid to perform assay, well-standardised by virtue of co-amplified internal system control RNA, provides a high specificity and positive predictive value for the diagnosis of HCMV disease in HIV-infected patients, comparable to that of the quantitative pp65-antigenemia assay and blood culture.

AIDS-Related Opportunistic Infections↗
PubMed2001

Human cytomegalovirus immediate-early messenger RNA in blood of pregnant women with primary infection and of congenitally infected newborns.

Human cytomegalovirus (HCMV) immediate-early messenger RNA (IEmRNA) in sequential blood samples from 32 pregnant women with primary infection and from 14 congenitally infected newborns was qualitatively investigated by nucleic acid sequence-based amplification. IEmRNA was detected in 100%, 75%, 36.3%, 22.2%, and 0% of samples collected 1, 2, 3, 4-6, and >6 months after onset of primary HCMV infection, respectively, showing 83.7% sensitivity and 92.2% specificity, compared with results of quantitative DNAemia (detection of viral DNA in blood). In infected newborns, IEmRNA was positive in 100% of samples collected 1-7 days (median, 1.5 days) and in 46.4% of samples collected 27-260 days (median, 88 days) after birth, showing 75.7% sensitivity and 100% specificity, compared with DNAemia results. IEmRNA was not detected in HCMV-immune individuals with remote or recurrent HCMV infection or in uninfected newborns. IEmRNA determination appears to be a valuable tool for early diagnosis of both primary and congenital HCMV infection.

Adolescent↗
PubMed2001

Expression dynamics of human cytomegalovirus immune evasion genes US3, US6, and US11 in the blood of lung transplant recipients.

Delayed elimination of human cytomegalovirus (HCMV)-infected cells by the host immune system may contribute to viral dissemination and pathogenesis of HCMV infection. The mRNA expression dynamics of HCMV-encoded immune evasion genes US3, US6, and US11 expressed after active HCMV infection were analyzed in blood samples of lung transplant recipients by means of quantitative nucleic acid sequence-based amplification. The results were compared with the expression dynamics of IE1 mRNA and pp67 late mRNA, levels of pp65 antigenemia, and antiviral treatment. During acute infection, high levels of US3 and US6 RNA were detected before antigenemia, which were detected simultaneously with IE1 RNA. US11 RNA was detected simultaneously with antigenemia but before late pp67 RNA. These data suggest an active role of viral immune evasion during HCMV infection in vivo. Interestingly, immune evasion RNA remained detectable after clinical recovery, often independently of IE1 RNA expression, indicating persistent viral activity, which may have implications for long-term control of HCMV.

Antigens, Viral↗
PubMed2001

Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients.

Posttransplant lymphoproliferative disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)-associated complication in transplantation recipients that is caused by iatrogenic suppression of T-cell function. The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectively collected unfractionated whole blood and serum samples of lung transplantation (LTx) recipients with and without PTLD. In PTLD patients, 78% of tested whole blood samples were above the cut-off value of quantitative competitive polymerase chain reaction (Q-PCR) (greater than 2000 EBV DNA copies per mL blood), with the majority of patients having high viral loads before and at PTLD diagnosis. Especially in a primary EBV-infected patient and in patients with conversion of immunosuppressive treatment, rapid increases in peripheral blood EBV DNA load diagnosed and predicted PTLD. In non-PTLD transplantation recipients, only 3.4% of the whole blood samples was above the cut-off value (P <.0001) despite heavy immune suppression and cytomegalovirus (CMV)-related disease. These findings illustrate the clinical importance of frequent EBV DNA load monitoring in LTx recipients. The increased EBV DNA loads in PTLD patients were restricted to the cellular blood compartment, as parallel serum samples were all below cut-off value, which indicates absence of lytic viral replication. EBV(+) cells in PTLD patients have a very short doubling time, which can be as low as 56 hours, thereby creating the need for high screening frequency in high-risk patients. Furthermore, it is shown that EBV and CMV can reactivate independently in LTx recipients and that EBV DNA load monitoring may be useful in discriminating PTLD from rejection.

Adult↗