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Biomedical subjects

V Jansen

Publications and source records attributed to V Jansen.

At least 19 recordsLinked to original sources

[Plasma concentration of endothelin-1 after myocutaneous latissimus dorsi-transplantation -- role in reperfusion injury].

The success of a free flap transplantation is based on a sufficient microanastomosis which meets the following requirements: a pedicle placed without kinking or twisting, a good drainage, a well defined recipient vessel and integrity of the endothelium. The aim of this study was to determine whether operation-related ischaemia through flap transplantation and tourniquet induces an increase of Endothelin-1 plasma levels as one cause of vasospasm during microvascular procedures. We focused our attention in particular on the reperfusion period which is often limited to an irreversible perfusion failure of microcirculation due to free radicals, interleukin and Endothelin-1. Twenty-one patients with tissue injury of the lower leg were included in our study, fourteen underwent a latissimus dorsi muscle transplantation with a combined ischaemia, seven patients had a tourniquet ischaemia for tumour resection, debridement and local flap transfer. The duration of ischaemia varied due to the course of operation. The withdrawal of venous blood via central vein catheter, flap vein and wound bed followed a fixed time table pre- and post-reperfusion (T1: preoperative day via cubital vein, T2: 6th postoperative day, T3: 5 min, T4: 10 min, T5: 15 min, T6: 1 h post-declamping and after tourniquet ischaemia via central vein catheter and T7: within 5 min from the flap vein immediate after recharging the flap). The vessel anastomosis determined the withdrawal from the local wound bed. ET-1 in venous blood samples were measured with ELISA. The duration of ischaemia in the tourniquet group ranged from 22 min up to 210 min with a mean of 76.58 min and in the latissimus group from 87 min up to 203 min with a mean of 139.21 min. The mean ET-1 plasma concentration measured systemically before operation in the 21 patients was 0.51 +/- 0.08 pg/ml (Mean +/- SD). This result corresponds with data published in literature. The locally measured plasma levels of ET-1 after tourniquet and flap ischaemia were increased with 0.34 up to 3.90 pg/ml (0.95 +/- 0.79 pg/ml [Mean +/- SD]) for the tourniquet group and with 0.34 up to 14.87 pg/ml (1.85 +/- 3.64 pg/ml [Mean +/- SD]) for the latissimus group. This is an increase compared to systemically measured values as 0.75 +/- 0.06 pg/ml (Mean +/- SD) for the tourniquet group and 0.58 +/- 0.21 pg/ml (Mean +/- SD) for the latissimus group. We conclude that Endothelin-1 is increased locally in the early reperfusion period after free latissimus dorsi-transplantation.

Adult↗

[The use of regional anesthesia in orthopedics].

Regional anesthesia has its place in the perioperative pain management of orthopedic patients. A reduction in postoperative mortality and morbidity with regional anesthesia is acknowledged for subsets of patient populations. Single shot and continuous applications are techniques for providing regional analgesia. Continuous infusion of local anesthetics with catheter techniques provides for uninterrupted postoperative analgesia. The combination of regional and general anesthesia reduces the consumption of systemic anesthetics. The side effects of opioid therapy are thereby reduced. The inhibition of intraoperative stress reaction, especially with epidural anesthesia, helps to prevent or lower unwanted metabolic changes. Patient contentment with analgesic quality differs with the technique with which the regional anesthesia is applied (PDA, PCEA, IVRA, peripheral block, i.a. injection), and the medication (LA, opioid) used.

Anesthesia, Conduction↗

Carrier screening for Gaucher disease in couples of mixed ethnicity.

With the advent of mutational analysis for Gaucher disease, carrier screening has been incorporated into many Jewish genetic disease screening programs. Frequencies and mutations for Gaucher disease in non-Jewish populations are less well established and the detection rate of carriers are lower. Testing is problematic for resolving residual risk in a couple of mixed ethnicity. We report the testing choices made by 20 consecutive couples of mixed ethnicity where the Ashkenazi Jewish partner was identified to be a Gaucher disease gene carrier. Carrier studies of the non-Jewish partner were elected as follows: DNA studies alone, 5 (25%); enzymatic assay, 2 (10%); both, 6 (30%); no carrier studies, 7 (35%). Of the 7 couples not electing carrier studies, one was not in a pregnancy and 6 elected prenatal diagnosis in lieu of parental testing by enzymatic analysis of amniocytes. One couple elected parental carrier studies as well as prenatal diagnosis. All couples electing prenatal Gaucher determination had amniocentesis for other indications as well (4, advanced maternal age; 4, parental anxiety). We conclude that Gaucher screening is feasible for couples of mixed ethnicity if appropriate counseling and testing are offered.

Adult↗

Systemic levels contribute significantly to increased intraocular IGF-I, IGF-II and IGF-BP3 [correction of IFG-BP3] in proliferative diabetic retinopathy.

Increased intraocular levels of angiogenic growth factors such as insulin-like growth factor I (IGF-I) have been demonstrated in proliferative diabetic retinopathy (PDR). It is unclear whether increased leakage of the blood retina barrier or local synthesis primarily determine intraocular levels of IGFs in man, which is of special interest regarding possible therapeutic options with somatostatin analogues in PDR. This is the first study investigating parallelly serum and vitreous levels of IGF-I/II, IGF-BP3 and the liver-derived permeability marker albumin to determine in vivo the amount of circulation-derived intraocular IGFs. A control group without retinal proliferation and patients with PDR were compared. Levels of IGF-I/II, IGF-BP3 and albumin were determined by immunological methods. Vitreous levels of albumin were 2.2-fold elevated in patients with PDR (254.1 +/- 37.2mg/dl; n = 27; p = 0.0027) compared to controls (115.7 +/- 36.2mg/dl; n =10), whereas serum levels were slightly decreased in diabetes patients (5049 +/- 196 mg/dl vs. 4330 +/- 186 mg/dl; p = 0.0283). This was comparable to an increase of IGF-I/11 and IGF-BP3 in vitreous from PDR patients (IGF-I: 2.3 +/- 1.1 ng/ml p = 0.005. IGF-II: 37.9 +/- 4.9 ng/ml; p = 0.0003. IGF-BP3: 97.9 +/- 26.9 ng/ml; p = 0.0001; n = 34) compared to controls (IGF-I: 0.7 +/- 0.1 ng/ml. IGF-II: 21.3 +/- 4.2 ng/ml. IGF-BP3: 31.3 +/- 4.9 ng/ml: n = 19). Serum levels did not differ significantly among the groups regarding IGF-I, II and IGF-BP3. Intraocular albumin and IGF-I levels calculated as percentage of the respective serum levels correlated significantly (r = 0.42; p = 0.012). This study demonstrates that influx of IGF-I, II and IGF-BP3 in PDR quantitatively parallels influx of the liver derived serum protein albumin suggesting that leakage of the blood retina barrier and serum levels of IGF primarily determine intravitreal IGF levels rather than local synthesis. Suppression of systemic IGF levels by new, highly effective somatostatin-analogues therefore provides a promising approach to prevent PDR.

Aged↗

Carrier screening for cystic fibrosis, Gaucher disease, and Tay-Sachs disease in the Ashkenazi Jewish population: the first 1000 cases at New York University Medical Center, New York, NY.

BACKGROUND: By late 1993, the genes for cystic fibrosis and Gaucher disease and the mutations common among Ashkenazi Jews had been identified. In response to these advances, heterozygote screening for cystic fibrosis and Gaucher disease was added to the more than 20-year-old Tay-Sachs disease screening program at New York University Medical Center, New York, NY. OBJECTIVE: To review the outcomes from the first 1000 patients screened through this program. METHODS: Patients and their referring physicians were informed about the new carrier tests. At the time of screening, patients could choose their tests (hexosaminidase A by enzyme analysis for Tay-Sachs disease or mutation analysis for cystic fibrosis and Gaucher disease). All partners of Tay-Sachs and cystic fibrosis carriers were tested. Prenatal diagnosis was offered and performed for carrier couples or mixed-marriage couples in whom the Ashkenazi Jewish partner was a carrier of Gaucher disease. Outcomes were measured by: (1) choice of tests, (2) decisions regarding prenatal diagnosis, and (3) phenotypes of children born to patients who underwent screening. RESULTS: The majority of Ashkenazi Jewish patients chose to have testing for all 3 diseases. If they previously underwent screening for Tay-Sachs disease, then they chose to undergo testing for cystic fibrosis and Gaucher disease. All carrier couples for each of these diseases went on to have prenatal testing. All mixed-marriage couples in whom the Jewish partner was found to be a carrier for Gaucher disease chose to have prenatal diagnosis. One fetus was identified as having cystic fibrosis. Since the program was initiated, no Ashkenazi Jewish baby has been born with any of these diseases at New York University Medical Center. CONCLUSIONS: New tests can be readily incorporated into established heterozygote screening programs. The Ashkenazi Jewish population described herein tends to choose testing for all conditions for which heterozygote screening is available.

Cystic Fibrosis↗

Genetic screening of prospective oocyte donors.

OBJECTIVE: To report our experience with genetic screening of oocyte donor candidates and to determine the frequency with which significant genetic issues are identified. DESIGN: Prospective genetic screening of oocyte donor candidates. SETTING: University hospital oocyte donation program. PATIENT(S): Women presenting consecutively as volunteer oocyte donors. INTERVENTION(S): Genetic screening was performed by pedigree analysis and laboratory studies. MAIN OUTCOME MEASURE(S): Inclusion in the oocyte donor pool based on the results of clinical evaluation and laboratory tests consisting of polymerase chain reaction based mutational analysis for cystic fibrosis carrier status, cytogenetic analysis for karyotype, enzymatic assay for Tay-Sachs disease carrier status, and complete blood count and hemoglobin electrophoresis. RESULT(S): Eight (11%) of 73 oocyte donor candidates were excluded from the donor pool because of a potentially serious genetic finding. Cystic fibrosis mutations were identified in 5 candidates (7%), abnormal karyotypes were found in 2 (3.5%), and an autosomal dominant skeletal dysplasia was identified in 1 (1.4%). CONCLUSION(S): A significant proportion of women who present as candidates for oocyte donation are inappropriate for donation because of their genetic history or genetic testing results. A thorough genetic evaluation, including a history and laboratory screening, is essential to any oocyte donation program to maximize positive outcomes in pregnancies achieved through assisted means.

Adolescent↗

Determination of endogenous growth factors in human wound fluid: temporal presence and profiles of secretion.

Growth factors are important substances in the central control of wound healing during the exudative phase. Although these peptides have been applied frequently to chronic wounds in clinical studies, little is known about the naturally occurring levels at the wound site in correlation to healing in superficial wounds. We have therefore investigated the presence of these cytokines in partial thickness wounds. In 16 patients undergoing reconstructive surgery, split-thickness skin wounds were enclosed in cutaneous vinyl chambers filled with 2.5 ml of saline. Chambers placed over unwounded skin served as controls. After 24 hours, the accumulated wound fluid was harvested and replaced by 2.5 ml of saline until the wounds were healed. Wound fluid was centrifuged, aliquoted, and frozen at -70 degrees C. Samples were analyzed for protein and growth factors (insulin-like growth factor-1, epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor-AB, interleukin-1alpha, and transforming growth factor-beta1 and -beta2) and insulin-like growth factor-binding proteins 1 and 3 using a monoclonal Sandwich enzyme-linked immunosorbent assay and radioimmunoassay. All wounds healed in the liquid environment within 7 days (macroscopically) and 11 days (barrier function), respectively. In wound fluid, protein concentrations dropped from 5 mg/ml on day 1 to a baseline of 0.1 mg (unwounded skin), indicating a return of the barrier function. All growth factors could be measured already after 24 hours postwounding. However, the concentrations measured varied from 10 to more than 10,000 pg/ml between the different factors. The highest range was found for insulin-like growth factor-1 (21,000 to 41,000 pg/ml), the lowest for epidermal growth factor (3 to 63 and 3 to 88 pg/ml, respectively). Two different patterns of kinetics were distinguished: (1) a high initial peak decreasing to baseline values or below serum levels by the time of healing (insulin-like growth factor-1, insulin-like growth factor binding protein-1, -3, basic fibroblast growth factor, epidermal growth factor, platelet-derived growth factor-AB, transforming growth factor-beta1) and (2) a low initial concentration followed by an increase to a maximum at the time of epithelialization (interleukin-1alpha, transforming growth factor-beta2). Comparing the growth factor levels measured to serum baseline values, it was found that four of the growth factors appeared in wound fluid at above serum concentrations (interleukin-1alpha, transforming growth factor-beta2, basic fibroblast growth factor, epidermal growth factor); the other factors never reached serum values in wound fluid (insulin-like growth factor, transforming growth factor-beta1, platelet-derived growth factor-AB). It is concluded that the different profiles of secretion might reflect different functions of polypeptide growth factors such as stimulation of epithelialization (epidermal growth factor, insulin-like growth factor-1), matrix synthesis (transforming growth factor-beta), and inflammatory stimulation (interleukin-1alpha). The concentrations determined could serve as guidelines for adapted administration of growth factors once correlations to healing disorders such as overhealing and ulceration are established.

Adult↗

Diagnosis of patent foramen ovale by transesophageal echocardiography and correlation with autopsy findings.

Transesophageal echocardiography (TEE) is accepted as the method of choice for the diagnosis of the patent foramen ovale (PFO). However, direct anatomic confirmation regarding the presence or absence of a PFO on transesophageal imaging has been obtained in only a limited number of patients. Consequently, this study was performed to assess the diagnostic accuracy of contrast and color Doppler TEE for detection of a PFO by comparing the results of TEE with autopsy. The study population comprised 35 consecutive patients (mean age 64 +/- 14 years) who underwent autopsy and prior TEE with examination of the atrial septum. For diagnosis of a PFO, the following criteria were used: (1) no defect in the continuity of the atrial septum on 2-dimensional imaging; (2) > or = 1 bright microbubble appearing in left the atrium within 3 heart cycles after opacification of the right atrium during contrast TEE; and (3) turbulent color jet within the atrial septum by color Doppler TEE. For estimating the PFO size, positive contrast studies were graded semiquantitatively (from 1 to 3), and the maximal color Doppler jet width was measured within the atrium septum at the area of maximal turbulence. At autopsy, a PFO was present in 9 of 35 patients (26%). All were correctly diagnosed by color Doppler TEE. The color Doppler jet width correlated well with the PFO diameter determined at autopsy (r=0.99, SEE=0.51 mm, p<0.0001). By contrast TEE, 8 of the 9 patients with autopsy-proven PFO were correctly identified. In 1 case with left heart disease and a long interatrial channel, a PFO was missed by contrast TEE but clearly demonstrated by color Doppler TEE. All patients with a PFO diameter >10 mm showed intense left atrial opacification of grade 3. With both methods, there were no false-positive results. Sensitivity and specificity for diagnosis of a PFO were 89% and 100% respectively, for contrast TEE, and both 100% for color Doppler TEE. Thus, contrast and color Doppler TEE are complementary and represent a highly sensitive and specific method for diagnosis of a PFO and for estimation of the PFO size.

Adult↗

Hypophysitis in surgical and autoptical specimens.

We present the clinical and histological findings of 11 cases of inflammatory anterior pituitary lesions, 8 of which were obtained during surgery and 3 of which were obtained from autopsies. Additionally, we extended the conventional classification of pituitary inflammatory disease by the new entity " secondary hypophysitis". Of the surgically obtained specimens 5 consisted of inflammatory extension into the pituitary gland out of the surrounding tissue. In all of these patients the inflammation originated from an additional tumor in the sellar region (4 craniopharyngiomas, 1 prolactinoma). These will be referred to as "secondary hypophysitis", an entity which has not yet been mentioned in the literature. Of the remaining 6 cases, 2 were granulomatous hypophysitis, 2 pituitary abscesses, 1 lymphocytic hypophysitis, and 1 showed extensive scarring of the anterior pituitary lobe due to preceeding lymphocytic hypophysitis. At histological examination the basic structure of the anterior pituitary was maintained in all cases. Relative counts of hormone-producing cells were normal. In secondary hypophysitis, the affected area was composed of fibrous tissue and granulation tissue. B and T lymphocytes were present in equal amounts. Granulomas were not found. Inflammatory infiltrates, granulation tissue and fibroses were seen in different proportions. Based on our results and three other cases reported in the literature so far, we think that the presently used classification of pituitary inflammatory diseases lacks an entity which describes a non-abscess-forming inflammation of the pituitary gland originating from an associated pathological process. Therefore, we introduced the term secondary hypophysitis to describe this fourth entity of pituitary inflammatory disease.

Adult↗

Glycosphingolipid expression on murine L1-fibrosarcoma cells: analysis of clonal in vivo and in vitro selected sublines with different lung colonisation potential.

The patterns of acidic and neutral glycosphingolipids (GSLs) were examined in a syngeneic tumour system in Balb/c mice consisting of closely related cell lines with different colonisation potentials directed to the murine lungs (in vivo selected highly metastatic sublines of L1-fibrosarcoma cells and their WGA-resistant mutants with low metastatic potential). GSLs were analysed by high-performance thin-layer chromatography and structurally identified by fast atom bombardment mass spectrometry combined with compositional analyses and exo-glycosidase digestion. The results suggest that highly metastatic sublines L1-LM and L1-LM12 derived by in vivo selection from mouse fibrosarcoma cells (cell line L1) exhibit a drastic increase of polar ganglioside expression and a restriction to globo-series GSLs. Contrasting with this the low metastatic mutant cells (L1-LM13WGA) express a reduced portion of acidic GSLs and exhibit a shift to less polar ganglioside components. Total cellular and plasma membrane-integrated GSLs were demonstrated to exhibit largely identical patterns. Concomitant with a significant decrease in LacCer expression a substantial reduction of GM2 and a complete lack of GM3 expression can be assigned to the highly metastatic sublines of L1-cells. On the other hand, the more polar gangliosides GM1a and, to an even greater extent, GD1a (exceeding 70% of total gangliosides) accumulate on L1-LM and their clonal sublines. The shift to acidic GSLs of higher polarity is less pronounced on the low metastatic WGA-resistant mutant cells (L1-LM13WGA) showing a preponderance of GM1a. The portion of GD1a within the fractions of acidic GSLs does not correspond to the cellular activities of CMP-NeuAc/GM1 (alpha 2-3) sialyltransferase measured for high and low metastatic cell variants. Total sialic acid content of the various cell lines differs, but is not associated with the metastatic potential. Gangliosides on L1-cells exhibit a significant substitution of N-glycolyl for N-acetylneuraminic acid (13%) compared to their metastatic sublines and to mutant cells (less than 1%). A conversion of surface exposed GD1a to GM1a on membranes of metastatic cells by in situ treatment with Vibrio cholerae sialidase is associated with a significant reduction of tumour cell colonisation directed to the murine lungs.

Animals↗

A rare case of 68,XX triploidy diagnosed by amniocentesis.

68,XX triploidy was found in the amniotic fluid cell culture of a 40-year-old patient. Elective termination of the pregnancy revealed a fetus with multiple congenital anomalies. While this case does show some common features with monosomy X, a greater similarity to the triploidy syndrome is observed.

Abnormalities, Multiple↗

alpha-Thalassemia hydrops fetalis: clinical and ultrasonographic considerations.

Five pregnant Southeast Asian women presenting during a 14-month period with microcytic anemia, preeclampsia, and size-date discrepancies were all ultimately diagnosed as carrying fetuses with homozygous alpha-thalassemia hydrops fetalis. The perinatal complications of this hemoglobin disorder are unique to persons of this ethnic background and include uniform fatality for the affected infant, maternal preeclamptic morbidity, and retained placenta. In this report the obstetric ultrasound findings are presented and the clinical manifestations are discussed, with recommendations made to reduce this emerging public health problem in the United States.

Adult↗

Hair root analysis in X-linked ichthyosis.

Hair roots have been analysed in a large kindred with X-linked ichthyosis associated with steroid sulphatase deficiency. Enzyme activity in individual hair roots was assayed for the steroid sulphatase:neutral alpha-glucosidase ratio, the latter serving as an indicator of the general metabolic activity of the hair root. The distribution of the enzyme ratios in the individual hair roots in the heterozygotes described a normal curve suggesting origin from a single population of cells. The results differed strikingly from the irregular distribution of enzyme activities in hair roots of Lesch-Nyhan disease, where mosaicism occurs. It is suggested that the maternal and paternal genes for steroid sulphatase remain active in vivo in each cell in the hair root in apparent contradiction to the Lyon hypothesis. The observation is consistent with that previously reported for skin fibroblasts in vitro. Sulphatase activity in female controls was minimally greater than in males but the difference was not statistically significant.

Female↗

Transfer of urea, sodium, and chloride across the perfused human placenta.

Clearance indices (clearance of experimental material: clearance of antipyrine, CI) across the perfused human placenta were determined for urea, sodium, and chloride. The selected materials are of relatively small molecular weight and are water soluble. Clearance of urea was determined under conditions of net transfer and of exchange and no difference was detected. Sodium and chloride clearances were measured as exchange rates. The CI were: urea, 0.32 and 0.38 toward fetus and mother, respectively); sodium, 0.28; and chloride, 0.41 (measured toward the fetus). Recalculation of data as the diffusion limitation (LD) facilitated comparison with data in the literature on the monkey, rabbit, and sheep. LD for urea was comparable among the four species whereas the sheep placenta differed, sharply limiting the diffusion of sodium and chloride. The discrepancy in the sheep between urea and sodium indicates that the low transfer rate of the latter cannot be explained by the "thickness" of the syndesmochorial placenta, as is often stated. Inferences concerning nitrogen metabolism in the fetus have been derived by others from data on transplacental urea gradients and urea clearance. Available data in the human are incomplete but are consistent with amino acids providing approximately 10% of fetal energy needs, with glucose serving as the predominant substrate.

Animals↗

Characterization of the (rnunz) nude rat. Morphological characteristics of the lymphoid system.

A nude mutant (rnunz) arose spontaneously in a colony of Wistar albino rats (the wild-type strain) in Wellington, New Zealand. On gross examination no thymus could be found in the mediastina of young animals, whereas in older mutants lobules of fatty tissue mimicked the appearance of the thymus of the wild-type strain. Lymph nodes from the rnunz strain showed a marked lymphocyte depletion in the thymus-dependent para-cortical region of the node. Peyer's patches from the nude animals also showed a reduced density of small lymphocytes in the interfollicular zones. In the spleen, tissue from the reticular framework surrounding individual arterioles was sometimes completely empty of lymphocytes but the degree of depletion varied. Total leucocyte numbers in the rnunz strain were 28% lower than the wild-type strain. In 10 out of 13 animals T cells were less than 3% of the lymphocytes present (wild-type 35% T cells). The findings are in agreement with studies of the Rowett nude rat (rnu) and the nude mouse.

Animals↗

Placental transfer of steroids: effect of binding to serum albumin and to placenta.

The transfer rates and placental retention of a series of steroids were measured using an in vitro perfusion system of an isolated cotyledon of human placenta. The steroids were added to the maternal inflow and rates of appearance in maternal and fetal outflows were measured, from which data were calculated the transfer rate and placental retention. With a low concentration of albumin (0.01 g/dl) in the maternal and fetal perfusates, transfer rates of diethylstilbestrol and ethynylestradiol were initially low, with considerable retention of the steroids within the placenta. Transfer rates increased with duration of perfusion. With high concentrations of albumin (1 g/dl), placental retention was greatly reduced and transfer rates very rapidly reached high levels. Albumin in the fetal circulation was the effective factor in increasing transfer rate; maternal albumin reduced it. The results with estrone and progesterone were qualitatively similar but not as striking, posssibly because of the large endogenous concentrations of these two hormones. Placental retention of dexamethasone, a more polar steroid that does not bind to placenta and binds poorly to albumin, was low and there was little difference between transfer from low- and high-protein perfusates.

Biological Transport↗