Biomedical subjects

Gauke Kootstra

Publications and source records attributed to Gauke Kootstra.

10 recordsLinked to original sources

PubMed2006

The Currarino triad: neurosurgical considerations.

OBJECTIVES: The Currarino triad, a relatively uncommon hereditary disorder, is often associated with tethered cord and anterior myelomeningocele. Little is known of the implications of these neuroanatomic malformations or of the neurosurgical attitude. The objective of this study is to identify the spinal cord and meningeal malformations associated with the Currarino triad and to discuss the risks and benefits of surgical intervention. METHODS: We analyzed the spinal cord malformations and the neurosurgical involvement with the Currarino triad by retrospective chart review. RESULTS: The Currarino triad neuroanatomic malformations were identified in five patients. The Currarino triad was associated with a tethered cord in three patients, a myelomeningocele in five patients, a syrinx in two patients, a fistula between the colon and spinal canal in two patients, and an Arnold-Chiari Type 1 malformation in one patient. CONCLUSION: Full spine imaging is required for all patients diagnosed with the Currarino triad. Magnetic resonance imaging of the head should be performed in every patient with neuroanatomic anomalies. Surgery of an anterior myelomeningocele is not necessarily indicated, only in the rare case in which the space-occupying aspect is expected to cause constipation or problems during pregnancy or delivery. Constipation directly after birth is seen in virtually all patients with the triad. Therefore, constipation cannot be used to diagnose a tethered cord syndrome nor indicate tethered cord release. Fistulas between the spinal canal and colon have to be operated on directly.

Abnormalities, Multiple↗

PubMed2005

The Currarino triad: the variable expression.

BACKGROUND: The Currarino triad is a relatively unknown hereditary disorder linked to the 7q36 region and characterized by an anorectal malformation, sacrococcygeal defect, and a presacral mass. PURPOSE: The aim of the study was to report the highly variable expression in patients with the Currarino triad and provide a guideline for the clinician if the Currarino triad is suspected. METHODS: We examined the symptoms and associated anomalies in 5 families with the Currarino triad by retrospective chart review. RESULTS: Fifteen patients had Currarino-associated anomalies. This included anorectal malformation in 9, a presacral mass in 9, and a sacral bone defect in 15. Tethered cord was present in 4 patients. There were 12 symptomatic patients. Constipation was diagnosed in all of them. Other symptoms included recurrent urinary tract infections caused by bladder dysfunction in 5, abnormal gait in 1, and another patient who initially presented with meningitis. Two carriers of the genetic defect had no symptoms or anomalies. CONCLUSIONS: The phenotypical expression of the gene mutations causing the Currarino triad can vary from asymptomatic to patients presenting with the complete triad. Presence of a crescent-shaped defect of the sacral bone may be used as initial screening method. As the penetration of the genetic defect is variable, DNA screening is the only method to fully exclude the triad.

Abnormalities, Multiple↗

PubMed2005

Repair of damaged organs in vitro.

Treatments that can be performed ex vivo following ischemia to accelerate cellular recovery and ameliorate reperfusion injury could have major impact. An acellular, near-normothermic perfusion was employed to deliver growth factors to ischemically damaged kidneys. During the treatment oxidative metabolism was sufficiently restored to support up-regulation of cellular processes with the potential to modulate both injury and repair proteins in damaged kidneys. The results suggest that growth factor administration, without concomitant inflammation, triggers pathways for new synthesis leading to cellular recovery rather than cell death.

Animals↗

PubMed2003

Induction of heme oxygenase-1 in kidneys during ex vivo warm perfusion.

BACKGROUND: Reperfusion injury plays a pivotal role in the occurrence of delayed graft function and chronic rejection. Heme oxygenase-1 (HO-1), an inducible heat shock protein, is known to have cytoprotective effects against reperfusion injury. We report on the potential for ex vivo induction of HO-1 expression during acellular warm perfusion of canine kidneys, using cobalt protoporphyrin (CoPP) as an HO-1 inducer and zinc protoporphyrin as an HO-1 inhibitor. METHODS: Canine kidneys were used to evaluate HO-1 increase after exposure to warm ischemia (WI), hypothermic perfusion (mechanical perfusion [MP], 4 degrees C), warm perfusion (exsanguineous metabolic support [EMS], 32 degrees C), or various combinations. RESULTS: WI alone, MP, or EMS with or without WI, had no effect on HO-1 activity. However, the presence of CoPP during EMS perfusion resulted in a significant increase in kidney HO-1 activity, whereas zinc protoporphyrin reduced HO-1 activity. The presence of CoPP during MP did not induce elevated HO-1 expression. The results of our study demonstrate that sufficient metabolism supporting new protein synthesis resulting in the expression of the protective gene, HO-1, can be accomplished during an acellular near-normothermic perfusion using CoPP. Most importantly, the time required for ex vivo HO-1 induction with this method is compatible with the current time frame for which organs are preserved clinically. CONCLUSIONS: The ability to induce HO-1 expression ex vivo eliminates the need for donor therapy to induce HO-1 increase before retrieving organs and also prevents the potential of decreasing HO-1 enzyme activity that is known to occur with temperature-mediated inhibition of oxidative metabolism during hypothermic organ storage.

Animals↗

PubMed2003

NOS: the underlying mechanism preserving vascular integrity and during ex vivo warm kidney perfusion.

Research involving metabolically active and functioning organs, maintained ex vivo in culture-like conditions, could provide numerous opportunities for medical innovations and research. We report successful perfusion of isolated canine and human kidneys ex vivo at near physiologic temperature for 48 h. During the perfusions parameters of metabolism and function remained stable. Nitric oxide synthase (NOS) was identified as the underlying mechanism preserving vascular integrity. Most importantly, when the canine kidneys were reimplanted there was immediate normal renal function. This report highlights the potential significance of whole organ culture using a warm temperature ex vivo perfusion and discusses medical applications that could be developed.

Animals↗

PubMed2002

Functional relationship of alpha-glutathione S-transferase and glutathione S-transferase activity in machine-preserved non-heart-beating donor kidneys.

alpha-Glutathione S-transferase (alpha-GST) is a biochemical parameter used to estimate the amount of proximal tubule damage to a kidney. In normal clinical practice, the concentration of alpha-GST in urine is determined by a rather time-consuming immunochemical test, the enzyme-linked immunosorbent assay (ELISA). Kidneys from non-heart-beating (NHB) donors are perfused prior to transplantation. The determination of alpha-GST concentration in the perfusate to monitor damage is also done by means of an ELISA test. However, because this is a time-consuming method, it would be helpful to find a parameter proportional to GST concentrations that would be available within minutes. We therefore compared the method of determining alpha-GST concentration via ELISA with that of determining the enzymatic activity of GST, which is much faster (results available within 10 min). The comparison was made using 150 preserved kidneys that had been perfused for 6 h. The correlation was found to be very good, as indicated by the linear regression data: r=0.954, P<0.001. pi-Glutathione S-transferase (pi-GST) was also determined by means of an ELISA test, and the concentration of pi-GST was compared with the enzymatic activity of the "total" GST. The precision of the enzymatic method, given by intra- and interassay variation, was 1.5% and 10.5%, respectively.

Enzyme-Linked Immunosorbent Assay↗

PubMed2002

Overcoming severe renal ischemia: the role of ex vivo warm perfusion.

BACKGROUND: The ability to effectively utilize kidneys damaged by severe (2 hr) warm ischemia (WI) could provide increased numbers of kidneys for transplantation. The present study was designed to examine the effect of restoring renal metabolism after severe WI insult during ex vivo warm perfusion using an acellular technology. After warm perfusion for 18 hr, kidneys were reimplanted and evaluated for graft function. METHODS: Using a canine autotransplant model, kidneys were exposed to 120 min of WI. They were then either reimplanted immediately, hypothermically machine perfused (4 degrees C) for 18 hr with Belzer's solution, or transitioned to 18 hr of warm perfusion (32 degrees C) with an acellular perfusate before implantation. RESULTS: Warm perfused kidneys with 120 min of WI provided life-sustaining function after transplantation, whereas the control kidneys immediately reimplanted or with hypothermic machine perfusion did not. The mean peak serum creatinine in the warm perfused kidneys was 3.7 mg/dl, with the mean peak occurring on day 2 and normalizing on day 9 posttransplant. CONCLUSIONS: These results indicate that 18 hr of ex vivo warm perfusion of kidneys is feasible. Furthermore, recovery of renal function during warm perfusion is demonstrated, resulting in immediate function after transplantation. The use of ex vivo warm perfusion to recover function in severe ischemically damaged kidneys could provide the basis for increasing the number of transplantable kidneys.

Animals↗

PubMed2002

Current opinions in horseshoe kidney transplantation.

Currently, horseshoe kidneys are also being considered for transplantation due to the shortage of organs. They can be transplanted en bloc or after division of the renal isthmus. However, because of their low incidence, horseshoe kidneys are rarely transplanted. The considerable variation in vascular anatomy of the horseshoe kidney add to both the frequency of primary non-function and the technical difficulty of the transplantation. In the study reported here, the surgical members of the European Society for Organ Transplantation were asked for their opinions regarding the techniques and results of horseshoe kidney transplantation. Most surgeons advised explanting the horseshoe kidney en bloc. The decision to transplant en bloc or after division of the renal isthmus depended on the morphology of the renal isthmus, the number and position of renal vessels and/or the anatomy of the urinary collecting system. Most surgeons thought that the results of horseshoe kidney transplantation were equal to those of normal kidneys.

Humans↗

PubMed2001

Organ donors: heartbeating and non-heartbeating.

The limits of organ donation from heart-beating (HB) donors reached a plateau illustrated by the number of postmortem kidneys for transplantation. Programs such as the European Donor Hospital Education Program (EDHEP) and Donor Action have helped to stop a further decrease in the number instead of an expected increase. For kidneys, heart, liver, and lungs one must also explore the use of marginal donors as a possible additional source. Examples are donors with a horseshoe kidney, those at both ends of the age spectrum, and those with medical contraindication such as diabetes. We have enlarged our kidney donor pool considerably with non-heart-beating(NHB) donors. Because we preserve these kidneys in a preservation machine, we are able to perform viability testing. With glutathione S-transferase (GST) as a measure of tubular damage, we now decide whether to transplant based on GST values. For other organs, NHB donation does not seem to be an option other than for the liver when the warm ischemia time is short.

Brain Death↗

PubMedDate not supplied

Solving the organ shortage: potential strategies and the likelihood of success.

The discrepancy between the demand and supply of organs for clinical transplantation remains a major problem. The current incidence of end-stage renal disease results in a patient population that doubles every decade. However, there have been no advancements in developing a comparable increase in the number of available allografts. There are three potential approaches to solving the shortage. In the near-term, the development of technology to access the pool of warm ischemically damaged organs may represent a solution. To achieve this goal, it will be necessary to develop technology that mimics the physiologic processes of wound repair. Alternatively, it has been proposed that an increased supply of organs can be developed with xenografts. To make xenotransplantation a clinical reality, it will be necessary to overcome the barriers that exist in nature between the species. Recent work in the area of stem cell research has provided evidence supporting the potential of generating biohybrid organs. A major undertaking of this emerging field will be to develop the ability to define and control the differentiation processes involved in organ specificity. The following is a review of the current status and relative issues involved with these three potential approaches to solving the organ shortage.

Animals↗