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Biomedical subjects

E Kirk

Publications and source records attributed to E Kirk.

At least 19 recordsLinked to original sources
PubMed2007

The accuracy of first trimester ultrasound in the diagnosis of hydatidiform mole.

OBJECTIVE: Previous studies have examined ultrasound findings in histopathologically confirmed cases of hydatidiform mole. The aim of this study was to assess the first-trimester ultrasonographic findings in all women suspected of having hydatidiform mole on ultrasound and those subsequently diagnosed with hydatidiform mole after histological examination of removed products of conception after surgical evacuation of the uterus. The aim was to obtain a true sensitivity and positive predictive value for ultrasound in the diagnosis of hydatidiform mole. METHODS: A retrospective analysis was performed of all cases of sonographically suspected hydatidiform mole and histologically proven hydatidiform mole presenting to the Early Pregnancy Unit of an inner city hospital over a 4-year period. The sensitivity and positive predictive value (PPV) of ultrasound in the detection of histologically proven hydatidiform mole was calculated. RESULTS: The study group consisted of 90 women; 56 were suspected of having hydatidiform mole on ultrasound, and of these 27 (48%) had hydatidiform mole confirmed after histopathological examination of the products of conception, while no changes suggestive of hydatidiform mole were present in the other 29 cases. Overall, 61 women had hydatidiform mole confirmed on histology-41 (67%) partial hydatidiform moles (PHM) and 20 (33%) complete hydatidiform moles (CHM). The ultrasound findings in the 34 cases not suspected of hydatidiform mole were an empty sac in 8/34 (24%) women and a delayed miscarriage in the other 26/34 (76%). The overall sensitivity and positive predictive value for the ultrasound diagnosis of hydatidiform mole was 44% and 48%, respectively. For PHMs the respective values were 20% and 22% and for CHMs they were 95% and 40%. CONCLUSION: Ultrasonography is more reliable for diagnosing CHMs than for PHMs. Overall, the sensitivity of ultrasound for accurately predicting hydatidiform mole is 44%, and one in two women with an abnormal scan will have the disease confirmed on histology.

Abortion, Spontaneous↗
PubMed2006

Prospective cross-validation of three methods of predicting failing pregnancies of unknown location.

BACKGROUND: We compared the performance of each of three tests for predicting pregnancy failure in the pregnancy of unknown (PUL) population. METHODS: In a prospective observational study, we compared the performance of three models for the prediction of pregnancy failure in women with a PUL: (i) logistic-regression model incorporating vaginal bleeding, endometrial thickness (ET), initial serum progesterone and hCG levels; (ii) serum progesterone at 0 h; and (3) the hCG ratio. RESULTS: A total of 5942 consecutive pregnant women attending the Early Pregnancy Unit were scanned and 439 (7.4%) were classified as PULs. Of these women, 420 had complete data for serum hCG at 0 and 48 h, the hCG ratio, serum progesterone at 0 h, vaginal bleeding and ET. The final outcomes were 219 (52.1%) failing PULs, 167 (39.8%) intra-uterine pregnancies and 34 (8.1%) ectopic pregnancies. For the prediction of pregnancy failure in the PUL population, the area under the receiver operating characteristic (ROC) curve (AUC) for the logistic-regression model was 0.907 (Standard error (SE) 0.015), the AUC for serum progesterone was 0.952 (SE 0.010) and the AUC for the hCG ratio was 0.980 (SE 0.004). This improved performance of the hCG ratio was significant when compared with that of initial serum progesterone (P = 0.0076) and the logistic-regression model (P < 0.0001). Using the hCG ratio cut-offs of < 0.87 and 70% for the prediction of failing PUL, sensitivities were 86.3 and 82.2% (S), 87.2% (NS) and 78.1% (S), specificities were 97.0 and 98.0% (NS), 89.6% (S) and 88.6% (S), positive-likelihood ratios were 28.91, 41.30, 8.34 and 6.82 and negative-likelihood ratios were 0.14, 0.18, 0.14 and 0.25, respectively. CONCLUSION: The hCG ratio seems to be an optimal test for the prediction of pregnancy failure in a PUL population. The hCG ratio cut-off of 0.79 is recommended on the basis of minimizing risk to those PULs discharged at 48 h. Most importantly, when the hCG ratio is below a particular cut-off, these women can be discharged at 48 h without intervention and need for further follow-up.

Adolescent↗
PubMed2006

A validation of the most commonly used protocol to predict the success of single-dose methotrexate in the treatment of ectopic pregnancy.

BACKGROUND: Currently, the likely success of single-dose methotrexate (MTX) (50 mg/m(2)) for the treatment of ectopic pregnancy is indicated by a >15% decrease in hCG from days 4-7 after administration. The aim of this study was to assess this protocol and to develop new rules that could be used to predict the outcome at an earlier stage. METHODS: Data were collected prospectively. Women receiving MTX for an ectopic pregnancy had serum hCG and progesterone levels checked on days 1, 3, 4, 5 and 7. Other factors including age, gestational age, previous obstetric history and ultrasound findings were recorded. The women were followed up until the outcome of medical management was known. Univariate analysis was performed to determine the benefit of the '15% day 4-7 rule', as well as to develop new rules, which potentially could be used to predict the likelihood of success before 7 days. Historical and ultrasound variables were also analysed to identify the significant variables associated with successful conservative management. RESULTS: The success rate of single-dose MTX was 68.1% (47/69). A second dose was required in 18.8% (13/69) of cases, and it was successful in 84.6% (11/13). The 15% day 4-7 rule correctly predicted the outcome in 90.3% of cases [sensitivity 93.0%, specificity 84.2%, positive predictive value (PPV) 93.0% and negative predictive value (NPV) 84.2%, Fisher exact test P-value < 0.0001]. New rules were developed based on the percentage change day 4-5 and logistic regression models incorporating day 5 hCG levels and ultrasound findings. These new rules did not outperform the current 15% day 4-7 rule. CONCLUSIONS: We have confirmed that a 15% decrease in serum hCG between day 4 and day 7 is a very good indicator of the likely success of MTX. The development of new rules did not significantly improve our ability to predict a successful outcome at an earlier stage.

Abortifacient Agents, Nonsteroidal↗
PubMed2006

There is no role for uterine curettage in the contemporary diagnostic workup of women with a pregnancy of unknown location.

BACKGROUND: The aim of this study was to generate and evaluate a new protocol that defined non-viability in the pregnancy of unknown location (PUL) population and therefore ensured no viable intra-uterine pregnancy (IUP) would be interrupted if uterine curettage was performed. A secondary aim was to evaluate published biochemical criteria that define non-viability in a PUL population to establish if these criteria could result in inadvertent termination of pregnancy (TOP) if uterine curettage was performed. METHODS: All clinically stable women classified as having a PUL were included in this study. Protocol 1 was developed retrospectively based on data from 500 consecutive PULs. Using this protocol, no cases of viable IUPs would undergo uterine curettage and the potential for TOP was eliminated. This protocol was then validated prospectively on the data from a further 503 consecutive PULs. Results were then compared with three established criteria (Protocols 2-4) for the use of uterine curettage as a diagnostic tool to classify the location of PULs. Protocol 2 defined non-viability when the hCG ratio (hCG at 48 h/hCG at 0 h) was or=2000 U/l or when the initial serum hCG was <2000 U/l with a serum hCG rise of <35% over 48 h (hCG ratio<1.35); Protocol 4 advised uterine curettage with a serum hCG rise of <50% over 48 h (hCG ratio<1.50). The number of uterine curettages performed and viable IUPs that would have undergone an unplanned TOP were recorded for all protocols. RESULTS: A total of 12 572 consecutive women were scanned: 1003 (8.0%) women were classified as PULs. Training set consisted of 500 PULs: 278 (55.6%) failing PULs, 176 (35.2%) IUPs and 46 (9.2%) ectopic pregnancies (EPs). Test set consisted of 503 PULs: 255 (50.7%) failing PULs, 203 (40.4%) IUPs and 45 (9.0%) EPs. Protocol 1 when developed retrospectively on the training set would have resulted in 293 uterine curettages and no potential TOP. Protocol 1 tested prospectively on 503 PULs would have resulted in 272 uterine curettages and no potential TOP. Three established criteria were tested on the entire data set (n=1003). Protocol 2 would have resulted in 114 uterine curettages and 14 (12.3%) potential TOPs; Protocol 3 would have led to 611 uterine curettages and seven (1.2%) potential TOPs; Protocol 4 would have resulted in 617 uterine curettages and three (0.5%) potential TOPs. No harm came to the women whose EP diagnosis was delayed. CONCLUSIONS: Established criteria for the use of uterine curettage in the management of PULs, including those advocated by the American Society for Reproductive Medicine (ASRM), can theoretically result in an inadvertent TOPs. On the basis of these data, a change in contemporary clinical practice should be considered to avoid further damage to wanted pregnancies. We conclude that uterine curettage should not be used in the routine diagnostic workup of women with a PUL.

Abortion, Spontaneous↗
PubMed2006

Predicting the outcome of pregnancies of unknown location: Bayesian networks with expert prior information compared to logistic regression.

BACKGROUND: As women present at earlier gestations to early pregnancy units (EPUs), the number of women diagnosed with a pregnancy of unknown location (PUL) increases. Some of these women will have an ectopic pregnancy (EP), and it is this group in the PUL population that poses the greatest concern. The aim of this study was to develop Bayesian networks to predict EPs in the PUL population. METHODS: Data were gathered in a single EPU from all women with a PUL. This data set was divided into a model-building (599 women with 44 EPs) and a validation (257 women with 22 EPs) data set and consisted of the following variables: vaginal bleeding, fluid in the pouch of Douglas, midline echo, lower abdominal pain, age, endometrial thickness, gestation days, the ratio of HCG at 48 and 0 h, progesterone levels (0 and 48 h) and the clinical outcome of the PUL. We developed Bayesian networks with expert information using this data set to predict EPs. RESULTS: The best Bayesian network used the gestational age, HCG ratio and the progesterone level at 48 h and had an area under the receiver operator characteristic curve (AUC) of 0.88 for predicting EPs when tested prospectively. CONCLUSIONS: Discrete-valued Bayesian networks are more complex to build than, for example, logistic regression. Nevertheless, we have demonstrated that such models can be used to predict EPs in a PUL population. Prospective interventional multicentre studies are needed to validate the use of such models in clinical practice.

Adolescent↗
PubMed2006

The non-surgical management of ectopic pregnancy.

Ectopic pregnancy can now be detected at earlier gestations in asymptomatic women. As a consequence conservative treatment strategies may be more appropriate than surgical intervention. This review aims to discuss the diagnosis and the non-surgical management options for ectopic pregnancy, in particular expectant management and the use of methotrexate.

Abortifacient Agents, Nonsteroidal↗
PubMed2006

The conservative management of cervical ectopic pregnancies.

OBJECTIVE: To evaluate the role of conservative management in the treatment of cervical ectopic pregnancies. METHODS: This was a retrospective analysis of all cervical ectopic pregnancies diagnosed in women attending our early pregnancy unit between April 1997 and September 2004 inclusive. The diagnosis of cervical ectopic pregnancy was made using transvaginal ultrasound. Clinical and demographic data were recorded in all cases. Serum human chorionic gonadotropin levels were measured at presentation and monitored subsequently to determine the rate of successful resolution. Conservative management was in the form of medical or expectant management. Medical management involved administration of systemic or intra-amniotic methotrexate, with or without intra-amniotic potassium chloride. Systemic methotrexate was either a single dose of 50 mg/m2 or an alternate-day regimen of methotrexate at 1 mg/kg (days 1,3,5) with folinic acid rescue (days 2,4,6). If intra-amniotic treatment was required, this was either 50 mg methotrexate or 5 mmol/L potassium chloride. RESULTS: Seven cervical ectopic pregnancies were diagnosed during the study period. Three cases were managed successfully with a single dose of methotrexate. One case was managed successfully using a multiple-dose methotrexate regimen. Another case failed medical management with both the single- and multiple-dose regimens but was successfully treated after potassium chloride was given intra-amniotically under ultrasound guidance. One case was successfully treated with intra-amniotic methotrexate and another was managed expectantly. There was no associated morbidity or mortality during the study period. We also performed a review of the current literature. CONCLUSION: The conservative management of cervical ectopic pregnancy is effective and safe.

Abortifacient Agents, Nonsteroidal↗
PubMed2006

The practical application of a mathematical model to predict the outcome of pregnancies of unknown location.

OBJECTIVE: A logistic regression model has been developed previously to predict which pregnancies of unknown location (PULs) become ectopics. This model was based on the human chorionic gonadotropin (hCG) ratio (hCG 48 h/hCG 0 h). The aim of this study was to evaluate the model in an early pregnancy clinical setting. METHODS: This was a prospective non-interventional observational study. Women classified as having a PUL had serum hCG and progesterone levels taken at presentation and 48 h later. At 48 h, nurse practitioners in the early pregnancy unit gave their subjective assessment of the likely pregnancy outcome based upon existing strategies to predict the outcome of PULs and their own previous experience. This was used as the basis for the clinical management of the women. The hormonal data were then entered into the model, which was available on the clinic computer in the form of a Microsoft Excel package, and the predicted outcome according to this model was recorded for each case. The model was weighted in favor of detecting an ectopic pregnancy at the expense of failing PULs and intrauterine pregnancies. All women were followed up until the final true diagnosis was established: a failing PUL, an intrauterine pregnancy or an ectopic pregnancy. The predicted outcome according to the model was compared with that of the subjective assessment of the expert operator and the true outcome after follow-up. RESULTS: Data were obtained from 357 women classified as having PULs. The final clinical outcomes were: 162 (45.4%) failing PULs, 166 (46.5%) intrauterine pregnancies and 29 (8.1%) ectopic pregnancies. Subjective assessment utilizing current strategies gave sensitivities of 79.3%, 92.8% and 87.0% for the detection of ectopic pregnancy, intrauterine pregnancy and failing PUL, respectively. The model detected ectopic pregnancy, intrauterine pregnancy and failing PUL with sensitivities of 82.8%, 86.8% and 73.5%, respectively. There were no adverse outcomes. CONCLUSION: This logistic regression model, based on the hCG ratio, can be used to predict the outcome of PULs, especially the ectopic pregnancies, with a high degree of certainty. It compares favorably with subjective assessment by experienced operators using current strategies to predict the outcome of PULs. The model can be used by those with limited knowledge or understanding of the behavior of serum biochemistry in the first trimester and in turn aid in the classification of PULs into those at low and those at high risk of ectopic pregnancy at 48 h.

Chorionic Gonadotropin↗
PubMed2006

Impact of the availability of sonography in the acute gynecology unit.

OBJECTIVE: The initial assessment of acute gynecology patients is usually based on history and clinical examination and does not involve ultrasound. The aim of this study was to investigate the impact of the availability of transvaginal sonography at the time of initial assessment of the emergency gynecology patient. METHODS: This was a prospective observational study carried out over a 5-month period in the acute gynecology unit of an inner London teaching hospital. Women were assessed in the routine manner by history-taking and clinical examination and questionnaires were completed by the doctors, including details of the intention to treat. Transvaginal ultrasound examinations were then performed and a second diagnosis and management plan were made utilizing the extra information from the scan. The plans for clinical management before and after the ultrasound examination were compared. RESULTS: We originally recruited 1000 consecutive women to the study. The mean age was 31.1 (SD, 9.81) years. Complete data were available for 920 (92%). 84 (9.1%) women did not require a scan. Of the 521 women with a positive pregnancy test, 75.6% were reassured immediately that their pregnancy was intrauterine. 143 women (27.4%) were given the diagnosis of a suspected ectopic pregnancy before sonography, compared with 29 (5.6%) after. Following the ultrasound examination there was a change in clinical management in 54.1% of the women with a positive pregnancy test and a reduction in admissions (including inpatient theater admissions) (from 40.3% to 17.1%) and outpatient follow-up examinations (from 41.1% to 35.5%). In 90 (23.8%) non-pregnant women a significant ovarian cyst (> 5 cm) was suspected clinically; 28/90 (31.1%) were confirmed on sonography. Following the ultrasound examination there was a change in clinical management for 38.1% of non-pregnant women and a reduction in admissions (from 37.1% to 19.4%) and outpatient follow-up examinations (from 25.7% to 18.1%). CONCLUSION: It appears that the availability of transvaginal sonography at the time of initial assessment of emergency gynecology patients improves diagnostic accuracy and reduces unnecessary admissions and follow-up examinations.

Adolescent↗
PubMed2006

Failing pregnancies of unknown location: a prospective evaluation of the human chorionic gonadotrophin ratio.

OBJECTIVE: To assess the performance of the human chorionic gonadotrophin (hCG) ratio (hCG 48 hours/hCG 0 hour) to predict spontaneous resolution of pregnancies of unknown location (PUL). DESIGN: Prospective cohort study. SETTING: Teaching Hospital Early Pregnancy Unit. POPULATION: Women classified as having a PUL. METHODS: The optimal cutoff value for hCG ratio (serum hCG at 48 hours/serum hCG at 0 hours) was calculated from data on 189 consecutive PULs (the 'training set'). This cutoff was tested prospectively on a further 200 consecutive PULs (the 'test set'). The hCG ratio was also compared to absolute levels of serum hCG at 0 and 48 hour for the prediction of failing PULs. MAIN OUTCOME MEASURES: hCG ratio in spontaneously resolving ('failing') PUL compared with those requiring intervention. Optimum cutoff determined and tested to predict spontaneously resolving PUL. Comparison of hCG ratio with absolute levels of serum hCG. RESULTS: A total of 3996 consecutive women were scanned, of which 438 (11.0%) were classified as PULs. Complete data were available for 389 women: 189 in the training set and 200 in the test set. In the training set, there were 102 (54%) failing PUL, while 109 (55%) in the test set. hCG ratio of <0.87 predicted failing PUL, with a sensitivity of 93.1% (95% CI 85.9-97.0) and a specificity of 90.8% (95% CI 82.2-95.7) in the training set. In the test set, sensitivity was 92.7% (95% CI 85.6-96.5) and specificity was 96.7% (95% CI 90.0-99.1). The hCG ratio outperformed absolute serum hCG levels at 0 and 48 hours. CONCLUSIONS: We have defined the optimal hCG ratio for the prediction of failing PUL. Using this cutoff, clinicians can safely adopt a noninterventional approach in women with PUL.

Biomarkers↗
PubMed2005

Do levels of serum cancer antigen 125 and creatine kinase predict the outcome in pregnancies of unknown location?

BACKGROUND: The aim of this study was to evaluate the role of maternal serum cancer antigen 125 (CA 125) and creatine kinase (CK) levels in predicting the outcome of pregnancies of unknown location (PUL). METHODS: Prospective observational study. Women classified as PUL were recruited. Final outcome of each PUL was established: failing PUL, intrauterine pregnancy (IUP), ectopic pregnancy (EP) or persisting PUL. The persisting PUL group almost certainly represent ultrasonically missed EP and were included in EP group. Serum CK and CA 125 were measured at 0 and 48 h. The values at presentation and the change in levels after 2 days were used in the analysis. We incorporated the most significant of variables into a multinomial logistic regression model to predict all outcomes. The performance of this model was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In all, 4698 consecutive women were scanned; 403 were classified as PUL, 27 were lost to follow-up. Of the 376 women eligible, 297 had complete data and therefore were recruited. Mean age and mean gestation were 30.0 years and 43.3 days respectively. Final outcomes: 153 failing PUL (51.5%), 116 IUP (39.1%) and 28 EP (9.4%). Mean serum CK levels at 0 and 48 h were 88.5 and 86.8 IU/l respectively. Mean serum CA 125 levels at 0 and 48 h were 43.8 and 40.1 kIU/l respectively. 81.1% of women had CK and CA 125 ratios (CK 48 h/CK 0 h, CA 125 48 h/CA125 0 h) between 0.7 and 1.3. CA 125 ratio was the only significant variable in the three outcome groups (P < 0.0001). Logistic regression analysis incorporating CA 125 ratio gave an area under ROC curve of 0.782 (SE = 0.041) for failing PUL, 0.768 (SE = 0.043) for IUP and 0.560 (SE = 0.078) for EP. This model was capable of distinguishing failing PUL from IUP, but was not able to detect EP. CONCLUSIONS: Absolute levels of serum CK and CA 125 at the defined times cannot be used to predict the outcome of PUL. Although the CA 125 ratio when incorporated into logistic regression model can distinguish failing PUL from IUP, its inability to detect the high risk PUL, i.e. the developing EP, renders it inappropriate for use in the clinical setting.

Age Factors↗
PubMed2005

Diagnostic accuracy of varying discriminatory zones for the prediction of ectopic pregnancy in women with a pregnancy of unknown location.

OBJECTIVES: Various serum human chorionic gonadotropin (hCG) discriminatory zones are currently used for evaluating the likelihood of an ectopic pregnancy in women classified as having a pregnancy of unknown location (PUL) following a transvaginal ultrasound examination. We evaluated the diagnostic accuracy of discriminatory zones for serum hCG levels of > 1000 IU/L, 1500 IU/L and 2000 IU/L for the detection of ectopic pregnancy in such women. METHODS: This was a prospective observational study of women who were assessed in a specialized transvaginal scanning unit. All women with a PUL had serum hCG measured at presentation. Expectant management of PULs was adopted. These women were followed up with transvaginal ultrasound, monitoring of serum hormone levels and laparoscopy until a final diagnosis was established: a failing PUL, an intrauterine pregnancy (IUP), an ectopic pregnancy or a persisting PUL. The persisting PULs probably represented ectopic pregnancies which had been missed on ultrasound and these were incorporated into the ectopic pregnancy group. Three different discriminatory zones (1000 IU/L, 1500 IU/L and 2000 IU/L) were evaluated for predicting ectopic pregnancy in this PUL population. RESULTS: A total of 5544 consecutive women presented to the early pregnancy unit between 25 June 2001 and 14 April 2003. Of these, 569 (10.3%) women were classified as having a PUL, 42 of which were lost to follow up. Of the 527 (9.5%) cases with PUL analyzed, there were 300 (56.9%) failing PULs, 181 (34.3%) IUPs and 46 (8.7%) ectopic pregnancies. Overall, 74.6% were symptomatic and 25.4% were asymptomatic (P = 8.825E-07). The sensitivity and specificity of an hCG level of > 1000 IU/L to detect ectopic pregnancy were 21.7% (10/46) and 87.3% (420/481), respectively; for an hCG level of > 1500 IU/L these values were 15.2% (7/46) and 93.4% (449/481), respectively, and for an hCG level of > 2000 IU/L they were 10.9% (5/46) and 95.2% (458/481), respectively. CONCLUSIONS: Varying the discriminatory zone does not significantly improve the detection of ectopic pregnancy in a PUL population. A single measurement of serum hCG is not only potentially falsely reassuring but also unhelpful in excluding the presence of an ectopic pregnancy.

Biomarkers↗
PubMed2001

Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a domain important for host cell recognition.

Several recent studies have established an association between abnormalities of complement factor H (FH) and the development of hemolytic uremic syndrome (HUS). To identify the relative importance of mutations in FH as a cause of HUS, we have undertaken mutation screening of the FH gene in 19 familial and 31 sporadic patients with FH. Mutations were found in two familial and three sporadic patients, and these clustered in exons 18-20, a domain important for host recognition. Moreover, this study demonstrates that familial HUS is likely to be a heterogeneous condition.

Amino Acid Sequence↗
PubMed2000

Postnatal development of NR1, NR2A and NR2B immunoreactivity in the visual cortex of the rat.

N-Methyl-D-aspartate receptors (NMDARs) are critically involved in some types of synaptic plasticity. The NMDAR subunits NR1, NR2A and NR2B are developmentally regulated, and it has been proposed that developmental changes in their expression may underlie developmental changes in cortical plasticity. Age-dependent change in cortical plasticity is most commonly measured by the monocular deprivation effect, which occurs during a critical period between P22 and P50 in the rat. Although the development of NMDAR subunits has been studied from birth through the fourth postnatal week, there is only meager information from older ages when visual plasticity ends. We hypothesized that there will be significant age-dependent change in expression of NR1, NR2A or NR2B between P22, when the cortex is plastic, and P90, when it is not. We applied specific antibodies recognizing NR1, NR2A and NR2B to the primary visual cortex at P14, P22, P30, P45 and P90. We found age-dependent changes in NR1-IR that were negatively correlated with changes in NR2A-IR; these subunits are not regulated in unison. In contrast, NR2A-IR and NR2B-IR were positively correlated. NR2A-IR and NR2B-IR both passed through a developmental minimum around P45, then recovered to approximately their P22 level. NR1-IR passed through a maximum at P45. There were no significant differences between P22 and P90. These results do not support the simple hypothesis that the loss of plasticity corresponds to a simple transition from juvenile levels of NMDAR subunit proteins to new adult levels. On the other hand, the results do confirm the hypothesis that there are significant changes in processing of NMDAR proteins during the time that plasticity is lost. How these changes of IR relate to synaptic transmission and plasticity needs to be clarified.

Animals↗
PubMed2000

In vitro neurotoxic effects of 1 GeV/n iron particles assessed in retinal explants.

The heavy ion component of the cosmic radiation remains problematic to the assessment of risk in manned space flight. The biological effectiveness of HZE particles has yet to be established, particularly with regard to nervous tissue. Using heavy ions accelerated at the AGS of Brookhaven National Laboratory, we study the neurotoxic effects of iron particles. We exposed retinal explants, taken from chick embryos, to determine the dose response relationships for neurite outgrowth. Morphometric techniques were used to evaluate the in vitro effects of 1 GeV/a iron particles (LET 148 keV/micrometer). Iron particles produced a dose-dependent reduction of neurite outgrowth with a maximal effect achieved with a dose of 100 cGy. Doses as low as 10-50 cGy were able to induce reductions of the neurite outgrowth as compared to the control group. Neurite generation is a more sensitive parameter than neurite elongation, suggesting different mechanism of radiation damage in our model. These results showed that low doses/fluences of iron particles could impair the retinal ganglion cells' capacity to generate neurites indicating the highly neurotoxic capability of this heavy charged particle.

Animals↗
PubMed1999

Congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly: Cantú syndrome.

Cantú syndrome (hypertrichosis, osteochondrodysplasia, cardiomegaly) is a rare condition, previously reported in 13 patients. We report on two additional patients with this disorder. One of the patients had pulmonary hypertension of unknown cause which was responsive to steroid therapy. She also had unusual, deep plantar creases, not reported previously in Cantú syndrome. Autosomal recessive inheritance has been suggested previously on the basis of sib recurrence in one family and consanguinity in another. We have performed a segregation analysis based on all reported families to date; the data indicate autosomal recessive inheritance is unlikely. A new dominant mutation or microdeletion syndrome are more likely possibilities, sib recurrence possibly representing gonadal mosaicism.

Cardiomegaly↗