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Biomedical subjects

T Kohl

Publications and source records attributed to T Kohl.

At least 37 records · Page 2Linked to original sources

Syphilis 2001--a palaeopathological reappraisal.

The origin and subsequent spread of the treponematoses, especially that of venereal syphilis, has been the subject of considerable scientific attention. Various theories were put forth and palaeopathological specimens were used for their validation in recent times. One influential contribution was the paper by Baker & Armelagos in 1988. Numerous new findings and results on both sides of the Atlantic call for a new evaluation of the available osseous material. A review of the recent literature leads to the suggestion of a worldwide distribution of non-venereal treponemal disease since the emergence of Homo and to a first epidemic outbreak of venereal syphilis in Europe of the late 15th and the early 16th century, which was a time of change and enormous sexual liberty. Old World specimens with pathological alterations attributed to venereal syphilis and dated to precolumbian times seem to invalidate the Columbian theory and call for a more differentiated analysis of the phenomenon of syphilis than a theory based on a single factor can provide. With the help of molecular methods which now allow a positive identification of Treponema pallidum pallidum, causative agent of venereal syphilis, in palaeopathological material, it seems possible to elucidate the matter of origin and spread of syphilis further and to evaluate previous diagnoses of treponemal disease.

Anthropology, Physical↗

Multimodal fetal transesophageal echocardiography for fetal cardiac intervention in sheep.

BACKGROUND: The overall performance of available mechanical intravascular ultrasound catheters for fetal transesophageal echocardiography during fetoscopic fetal cardiac interventions in sheep has been limited by radioelectronic interference, low system frame rates, and low acoustic outputs. Therefore, a more reliable device is desired for human fetoscopic surgical procedures. METHODS AND RESULTS: We assessed the potential of a newly available 10-French phased-array intravascular ultrasound catheter for multimodal fetal transesophageal echocardiography in 5 fetal sheep between 78 and 98 days of gestation (term, 145 to 150 d). The intravascular ultrasound catheter was easily inserted through the mouth into the esophagus in all 5 sheep fetuses (mean weight, 600 g), and it permitted high-quality 2D imaging of the fetal heart in vertical imaging planes that were validated by MRI. Color Doppler and pulsed Doppler imaging permitted clear assessment of fetal cardiovascular flows and recording of velocity-time integral tracings of the fetal heart and great vessels. The vertical imaging planes were particularly useful to demonstrate interventional material inside the fetal heart and great vessels. CONCLUSIONS: Our early experience with the phased-array intravascular ultrasound catheter indicates that multimodal fetal transesophageal echocardiography has now become possible in these smallest of patients.

Animals↗

In utero remodeling of the fetal lamb ductus arteriosus: the role of antenatal indomethacin and avascular zone thickness on vasa vasorum proliferation, neointima formation, and cell death.

BACKGROUND: The ductus arteriosus (DA) of newborn infants exposed in utero to indomethacin is resistant to postnatal indomethacin; we hypothesized that this is due to ductus constriction in utero, with subsequent remodeling of the vessel. METHODS AND RESULTS: Infusion of fetal lambs with indomethacin for 48 hours constricted the DA and increased the thickness of the avascular zone of the DA, which in turn induced the expression of vascular endothelial growth factor, endothelial nitric oxide synthase (due to ingrowth of vasa vasorum), neointima formation, and loss of smooth muscle cells; moderate degrees of DA constriction in utero increased NO production, which inhibited DA contractility. Marked degrees of DA constriction decreased tissue distensibility and contractile capacity. CONCLUSIONS: DA patency is no longer controlled primarily by prostaglandins once it has been exposed to indomethacin in utero.

6-Ketoprostaglandin F1 alpha↗

Fetoscopic direct fetal cardiac access in sheep : An important experimental milestone along the route to human fetal cardiac intervention.

BACKGROUND: Fetal cardiac interventions by direct ultrasound-guided approaches or open fetal cardiac surgery have been fraught with technical difficulties, as well as with significant maternal and fetal morbidity in humans. Therefore, the purpose of our study in sheep was to assess the feasibility and potential of fetoscopic direct fetal cardiac access. METHODS AND RESULTS: In 15 anesthetized pregnant ewes (88 to 109 days of gestation; term, 145 days), 3 to 4 trocars were percutaneously placed in the uterus. Using videofetoscopic equipment, we assessed the feasibility of achieving direct fetal cardiac access. Minimally invasive direct fetal cardiac access by operative fetoscopy was achieved in 10 of the 15 fetal sheep. In 7 fetuses, the approach was successfully tested for fetal cardiac pacing (n=5) or antegrade fetal cardiac catheterization (n=2). Access was not achieved in 5 fetuses because of bleeding complications (n=2) or because the fetoscopic setup could not be established (n=3). All but 2 fetal sheep were alive at the end of the procedure. Acute fetal demise resulted from maternal hypotension or kinking of the fetal inferior caval vein by sternal suspension. Six ewes continued gestation; 3 of these went to term, with a normal fetal outcome. Two ewes died from septicemia 3 and 7 days after the procedure, and 1 ewe aborted 1 month after the procedure. CONCLUSIONS: Minimally invasive direct fetal cardiac access by operative fetoscopy is feasible in fetal sheep. The fetoscopic approach carries important potential for fetal cardiac pacing, antegrade fetal valvuloplasties, and resection of fetal intrapericardial teratomas in human fetuses.

Animals↗

World experience of percutaneous ultrasound-guided balloon valvuloplasty in human fetuses with severe aortic valve obstruction.

Prenatal alleviation of severe fetal aortic valve obstructions by percutaneous ultrasound-guided balloon valvuloplasty has been performed to improve the fate of affected fetuses. The purpose of this study was to analyze the current world experience of these procedures in human fetuses. Data from 12 human fetuses were available for analysis. The mean gestational age at intervention was 29.2 weeks (range 27 to 33). The mean time period between initial presentation and intervention was 3.3 weeks (range 3 days to 9 weeks). Technically successful balloon valvuloplasties were achieved in 7 fetuses, none of whom had an atretic valve. Only 1 of these fetuses remains alive today. Of the 5 remaining technical failures, 1 patient with severe aortic stenosis underwent successful postnatal intervention and remains alive. Six patients who survived prenatal intervention died from cardiac dysfunction or at surgery in the first days or weeks after delivery. Four fetuses died early within 24 hours after the procedure, 1 from a bleeding complication, 2 from persistent bradycardias, and 1 at valvotomy after emergency delivery. Thus, the early clinical experience of percutaneous ultrasound-guided fetal balloon valvuloplasty in human fetuses with severe aortic valve obstruction has been poor due to selection of severe cases, technical problems during the procedure, and high postnatal operative mortality in fetuses who survived gestation. Improved patient selection and technical modifications in interventional methods may hold promise to improve outcome in future cases.

Aortic Valve↗

Operative techniques and strategies for minimally invasive fetoscopic fetal cardiac interventions in sheep.

BACKGROUND: Recent efforts to develop procedures for fetoscopic fetal cardiac interventions have been prompted by the development of severe secondary damage to the fetal heart due to semilunar valvar obstructions and the poor outcome of therapy-refractory fetal arrhythmias. The purpose of our manuscript is to analyze and share our experience with the creation of an operative setup for these procedures in sheep. METHODS: We studied a total of 48 fetal sheep between 81 and 106 days of gestation (term, 145 days). After entering the amniotic cavity by a percutaneous approach, we performed various fetoscopic fetal cardiac procedures. We analyzed the success of percutaneous fetal access, methods of trocar support, the incidence and management of trocar dislodgement or accidental insertion into the chorioamniotic space, problems related to amniotic insufflation and trocar placement, as well as techniques for fetal posturing and uterine closure. RESULTS: Percutaneous fetal access was achieved in all sheep. The use of resterilizable trocars substantially decreased the costs of our procedures. Utilizing a percutaneous transuterine purse-string suture for trocar support helped to minimize the number of nonabsorbable T-fasteners remaining inside the uterus postoperatively. As complications such as trocar dislodgement, insertion of the trocar into the chorioamniotic space, and problems with intraamniotic insufflation and gas loss were mastered, conversion to an open operative approach was never required. A novel strategy that we devised for percutaneous fetal posturing permitted adequate fetal posturing with ease and minimal trauma to the fetal skin. CONCLUSION: As operative techniques have become more refined, the feasibility of performing fetoscopic fetal cardiac interventions in human fetuses now depends mainly on technical improvements in imaging and interventional catheters, as well as advances in pacemaker equipment.

Animals↗

Fetoscopic transesophageal electrocardiography and stimulation in fetal sheep: a minimally invasive approach aimed at diagnosis and termination of therapy-refractory supraventricular tachycardias in human fetuses.

BACKGROUND: Therapy-refractory supraventricular tachycardia commonly results in hydrops and death in human fetuses. The purpose of this study in fetal sheep was to assess the feasibility of a minimally invasive fetoscopic approach for fetal transesophageal electrocardiography and stimulation aimed at diagnosis and termination of these tachycardias. METHODS AND RESULTS: We studied a total of 10 fetal sheep (87 to 103 days of gestation; term=145 days). We entered the amniotic cavity using a percutaneous fetoscopic approach and placed various electrophysiology catheters into the fetal esophagus. We recorded the number of animals in which fetoscopic transesophageal electrocardiography and stimulation were successful and assessed pacing success and thresholds for different catheters. In addition, we monitored for potential adverse effects from stimulation and for other complications of the operation. Recording of transesophageal electrocardiograms was successful in all fetal sheep. Capture during stimulation was successfully documented by additional fetal bipolar surface electrocardiograms in 7 fetuses. In fetuses in which fetal surface electrocardiograms were not recorded, pacing stimulus artifacts interfered with documentation of capture. Although stimulation thresholds were high, the maternal rhythm was not affected by fetal stimulation. CONCLUSIONS: Fetoscopic fetal transesophageal electrocardiography and stimulation are feasible in fetal sheep. This minimally invasive approach might have the potential to improve diagnosis and management of therapy-refractory supraventricular tachycardias in human fetuses.

Animals↗

Fetal transesophageal echocardiography utilizing a 10-F, 10-MHz intravascular ultrasound catheter--comparison with conventional maternal transabdominal fetal echocardiography in sheep.

The purpose of our study in fetal sheep was to assess the measurement agreement between fetal transesophageal echocardiography (FTEE) and conventional maternal transabdominal echocardiography (CMTFE) by the Bland-Altman method. We performed our study in 11 fetal sheep between 95-103 days of gestation (term = 145 days). FTEE was performed by imaging the fetal heart in horizontal planes utilizing a 10-F, 10-MHz intravascular ultrasound catheter. CMTFE was carried out using a 5.0-MHz phased-array transducer replicating the FTEE imaging planes. We found close agreement between FTEE and CMTFE measurements of great vessel and cardiac valvar dimensions. Conversely, the variability between both techniques for measuring ventricular dimensions was inadequate. We conclude that FTEE permits measurement of great vessel and cardiac valve dimensions with high agreement with CMTFE measurements. This finding strengthens the applicability of FTEE as a monitoring tool during experimental open or fetoscopic fetal cardiac interventions.

Animals↗

Accuracy of prenatal echocardiographic diagnosis and prognosis of fetuses with conotruncal anomalies.

OBJECTIVES: The purpose of the study was to determine the accuracy of the prenatal echocardiographic diagnosis and prognosis of fetuses with conotruncal anomalies. BACKGROUND: The accuracy of prenatal echocardiographic diagnoses of cardiac lesions has been reported, but no previous reports specifically address fetal conotruncal anomalies. METHODS: Medical records of 61 fetuses, in which a fetal diagnosis of a conotruncal anomaly was made, were reviewed. Disease entities included were tetralogy of Fallot (TOF), double outlet right ventricle (DORV), transposition of the great arteries (TGA), and truncus arteriosus (TA). RESULTS: Fetal diagnosis was established at a median of 24.5 weeks' gestation. Termination of pregnancy was chosen in 31% (19/61) of cases. Postnatal assessment of the diagnosis was not obtained in 12 cases. Excluding two sets of conjoined twins, accurate prenatal diagnosis including definition of the great artery orientation was achieved in 36 of 47 cases (77%). Seven of 17 fetuses with DORV anatomy, of which 6 were thought to have a subpulmonary ventricular septal defect (VSD), had incorrect prenatal assessment of the great artery relationships. One fetus thought to show features of TA had aortic atresia with VSD and normal-sized left ventricle. Of the 42 pregnancies that continued, 15 had major extracardiac malformations and/or chromosomal abnormalities of which one died in utero with trisomy-13 and TA. A further nine died within the neonatal period. Among the 27 fetuses without a documented chromosomal or major extracardiac anomaly, 13 (48%) died. Overall, the survival rate beyond 28 days of life was 52% (22/42). In contrast, 75% (6/8) of fetuses with TOF, excluding the absent pulmonary valve syndrome, survived. CONCLUSIONS: Conotruncal anomalies can be diagnosed by prenatal echocardiography with a high degree of accuracy. Defining the exact spatial relationship of the great arteries is problematic in some fetuses. The overall prognosis for fetuses with a conotruncal anomaly is poor, with the exception of uncomplicated TOF.

Abnormalities, Multiple↗

A simple new model of physiologically working heterotopic rat heart transplantation provides hemodynamic performance equivalent to that of an orthotopic heart.

BACKGROUND: The widely used non-volume-loaded abdominal heterotopic heart transplant (NL) in rats undergoes atrophy after transplantation. Various techniques have been designed to load the transplanted heart because of its potential immunological impact. Our aim was to create a volume-loaded heterotopic heart transplantation model (VL) capable of ejection and practical for routine studies. Using this model, we tested the hypothesis that VL isografts would retain myocardial performance comparable to native hearts (NH). METHODS: Heterotopic hearts were transplanted using and end-to-side anastomosis between the donor's superior vena cava and the recipient's abdominal inferior vena cava. The right ventricle loads the left ventricle (LV) via a direct anastomosis of the pulmonary artery to the left atrium. The LV ejects volume through an end-to-side anastomosis of the donor's aorta to the recipient's abdominal aorta. Hemodynamic data (systolic and diastolic LV pressures, dP/dt max and min, tau) were studied in-situ (at baseline and after adding volume) and in a Langendorff perfusion system (at baseline and after stimulation with isoproterenol) 2 weeks after transplantation. RESULTS: In situ systolic pressure and diastolic function of VL was superior to NL, and beta-adrenergic stimulated performance in the Langendorff perfusion of VL showed hemodynamic performance equivalent to NH, unlike NL which had a diminished response. CONCLUSION: This technique results in a volume-loaded ejecting heart transplant model that preserves anatomical structures. The VL can be evaluated in situ and after explantation in Langendorff perfusion system and may offer advantages if workload of the graft is of significance to the study performed.

Abdomen↗

Echocardiographic predictors of poor outcome in infants with hypertrophic cardiomyopathy.

Although hypertrophic cardiomyopathy (HC) is readily diagnosed by echocardiography in infants with isolated ventricular hypertrophy, echocardiographic predictors of outcome have not been described in this age group. To identify echocardiographic predictors of poor outcome of infants with HC, we reviewed medical records and echocardiograms of all 19 patients with HC aged <1 year seen at the University of California, San Francisco, from January 1981 through December 1995. Thickness of the ventricular septum and the left ventricular (LV) posterior wall, ventricular septum/LV posterior wall ratio, LV mass, LV volume, LV mass/volume ratio, LV ejection fraction, and right ventricular anterior wall thickness were measured. The median age at diagnosis was 1 day; 11 were boys and 8 were girls. Within 1 year after birth, 10 patients died: the other 9 patients have survived to > 12 months of age. At the initial postnatal examination, the Z value for LV posterior wall was larger (median, 5.2 vs 1.3, p <0.04) and, consequently, the ventricular septum/LV posterior wall ratio was lower (1.6 vs 2.3, p <0.04) in nonsurvivors than in survivors. In serial studies, the Z value for both the ventricular septum and the LV posterior wall thickness increased in nonsurvivors, but decreased in survivors. Nonsurvivors had intrinsic metabolic disease or Noonan syndrome. Survivors had classic HC or maternal diabetes. We conclude that, in infants with HC, early or progressive hypertrophy of the LV posterior wall is a predictor of poor outcome, regardless of associated disease.

Cardiac Catheterization↗

Fetoscopic and open transumbilical fetal cardiac catheterization in sheep. Potential approaches for human fetal cardiac intervention.

BACKGROUND: Shortening the prenatal disease course of severe aortic and pulmonary stenoses by balloon valvuloplasty may diminish their postnatal expression. The purpose of this study in fetal sheep was to assess the feasibility of fetoscopic and open transumbilical fetal cardiac catheterization guided by fetal transesophageal echocardiography to provide alternative approaches for human fetal cardiac intervention. METHODS AND RESULTS: We studied a total of nine fetal sheep (95 to 103 days of gestation; term = 145 to 150 days) and performed transumbilical fetal cardiac catheterization by a minimally invasive fetoscopic (n = 6) or an open fetal surgical approach (n = 3). Monitored by fetal transesophageal echocardiography, with an 8F or 10F, 10-MHz intravascular ultrasound catheter we placed guidewires and interventional catheters via the umbilical arterial route into the fetal heart. In three of the fetuses, we created supravalvar pulmonary artery stenosis by open fetal cardiac surgery After fetal and maternal recovery, we exteriorized these fetuses and performed open transumbilical fetal cardiac catheterization with successful pulmonary arterial angioplasty in two. Three fetuses survived fetoscopic transumbilical catheterization for 1 or 2 days and died most likely of blood loss after sheath dislodgment (n = 1) or removal (n = 2). By securing the sheath insertion site with a suture, we prevented sheath dislodgment and minimized bleeding during sheath removal in three fetuses. These fetuses then survived fetoscopic transumbilical fetal cardiac catheterization for 1 to 2 weeks before being killed. CONCLUSIONS: This study in fetal sheep demonstrates that fetoscopic and open transumbilical fetal cardiac catheterization are feasible and, guided by fetal transesophageal echocardiography, provide potential alternative approaches for human fetal cardiac intervention.

Angioplasty, Balloon↗

Percutaneous fetal access and uterine closure for fetoscopic surgery. Lessons learned from 16 consecutive procedures in pregnant sheep.

BACKGROUND: Maternal morbidity and preterm labor from fetal surgery might be minimized by a percutaneous technique for fetal access and uterine closure. METHODS: In each of 16 ewes, we inserted three trocars percutaneously into the amniotic cavity using ultrasound and fetoscopic guidance. In six ewes, percutaneous uterine closure after the procedure was attempted. We assessed feasibility and acute complications of our technique during surgery and at autopsy. RESULTS: We achieved percutaneous fetal access in 14 ewes and closed the uterus percutaneously in all six ewes attempted. Fetal injury was related to amnioinfusion or fixation of chorioamniotic membranes. Other complications were trocar dislodgment and damage to uterine wall and chorioamniotic membranes. The latter complication was prevented using balloon-tipped trocars. CONCLUSIONS: Percutaneous intraamniotic access and uterine closure for fetoscopic surgery can be achieved reliably with little maternal and fetal morbidity in sheep. Minor modifications are desired to apply this approach in humans.

Amnion↗

Fetal diaphragmatic hernia: echocardiography and clinical outcome.

It is difficult to predict survival of fetuses diagnosed prenatally with congenital diaphragmatic hernia. Some studies suggest that left heart underdevelopment is associated with poor outcome, but fetal echocardiographic variables have not been conclusively proven to be good predictors of postnatal survival. The authors reviewed detailed fetal echocardiographic studies in twelve fetuses with congenital diaphragmatic hernia. Ten echocardiographic variables, including left and right ventricular width, left ventricular volume, and left ventricular mass, were examined from a four-chamber view, corrected for gestational age, and compared with normal data. The results of this study showed no significant differences between survivors and nonsurvivors in the ten variables analyzed. Although left heart dimensions and left ventricular volume in fetuses with congenital diaphragmatic hernia were below the expected normal range, these results did not predict postnatal outcome.

Echocardiography↗

Experimental fetal transesophageal and intracardiac echocardiography utilizing intravascular ultrasound technology.

Fetal transesophageal and intracardiac echocardiography by utilizing ultrasound technology permits accurate definition of cardiac anatomy in fetal sheep. Because fetal transesophageal echocardiography is less invasive than intracardiac echocardiography, it has the potential to serve as a monitoring tool for currently developed open and fetoscopic fetal cardiac interventions.

Animals↗

Comparison of cleft and papillary muscle position in cleft mitral valve and atrioventricular septal defect.

Differentiation of cleft mitral valve from atrioventricular septal defect (AVSD) is surgically important because of different conduction pathways. The purpose of this study was to find echocardiographic markers for differentiating cleft mitral valve from AVSD. We examined 11 children with cleft mitral valve, 11 children with AVSD, and 11 normal children. We defined a fixed reference point (0 degrees of arc) at the medial junction of the right ventricular free wall with the posteroinferior ventricular septum. Left ventricular papillary muscle and cleft position was measured clockwise in degrees of arc from 0 degrees around a point representing the center of the left ventricle in the parasternal short-axis views. Mural leaflet size was expressed by the arc between the bases of the papillary muscles. Papillary muscle position in cleft mitral valve was similar to that in normals (anterolateral ventricular papillary muscle:cleft mitral valve 194 +/- 10 degrees, normals 191 +/- 8 degrees; posteromedial ventricular papillary muscle:cleft mitral valve 329 +/- 10 degrees, normals 329 +/- 14 degrees). In AVSD, both left ventricular papillary muscles originated closer to each other and were rotated counterclockwise (anterolateral papillary muscle: 182 +/- 7 degrees; posteromedial papillary muscle: 287 degrees +/- 17 degrees). The mural leaflet size was similar in cleft mitral valve and in normal children. In AVSD, the mural leaflet was significantly smaller than in cleft mitral valve and in normals. The cleft position did not permit distinction between cleft mitral valve and AVSD. In conclusion, echocardiographic measurements of papillary muscle position and mural leaflet size permit differentiation of cleft mitral valve from AVSD.

Child↗

Transesophageal echocardiography in fetal sheep. A monitoring tool for open and fetoscopic cardiac procedures.

BACKGROUND: Cardiac procedures in exteriorized fetuses or assisted by fetoscopy require monitoring capabilities not attended by conventional maternal transabdominal echocardiography. METHODS: We, therefore, assessed the potential of fetal transesophageal echocardiography (TEE) utilizing an intravascular ultrasound catheter (IVUC) for fetal cardiac monitoring. We inserted a 10-F-10-MHz IVUC into the esophagus in 12 exteriorized fetal sheep and by a fetoscopic approach in 4 fetal sheep. Cardiac events were observed. Heart rate, cardiac rhythm, patency of the foramen ovale and ductus arteriosus, and the width of the branch pulmonary arteries could be assessed in all fetuses. Ventricular contractility could be assessed only in fetuses weighing less than 2.5 kg. Larger fetuses did not allow adequate imaging of the apical portion of the ventricles because of limited tissue penetration of the IVUC. Fetal TEE permitted placing small guide wires in the cardiac atria and left ventricle. Short-lived premature beats following intracardiac manipulations of these wires could be observed by fetal TEE in all cases. RESULTS: At autopsy, no complications from IVUC insertion were observed in the exteriorized fetuses. Fetoscopic placement of the IVUC resulted in minor perioral skin erosion in two nonexteriorized fetuses. CONCLUSIONS: In conclusion, fetal TEE can be achieved with minor fetal injury and may provide useful information during open and fetoscopic cardiac procedures. Further improvements in IVUC design will permit the application of this technique to monitor human fetal cardiac procedures.

Animals↗