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D Blom

Publications and source records attributed to D Blom.

18 recordsLinked to original sources
PubMed2004

Correlation of radiographic and manometric findings in patients with ineffective esophageal motility.

BACKGROUND: Ineffective esophageal motility disorder (IEM) is a new, manometrically defined, esophageal motility disorder, associated with severe gastroesophageal reflux disease (GERD), GERD-associated respiratory symptoms, delayed acid clearance, and mucosal injury. Videoesophagram is an important, inexpensive, and widely available tool in the diagnostic evaluation of patients with esophageal pathologies. The efficacy of videoesophagography has not been rigorously examined in patients with IEM. The aim of this study was to determine the diagnostic value of videoesophagography in patients with IEM. METHODS: The radiographic and manometric findings of 202 consecutive patients presenting with foregut symptoms were evaluated. IEM was defined by strict manometric criteria. All other named motility disorders such as achalasia were excluded. Videoesophagography was performed according to a standard protocol. RESULTS: Of patients in this cohort, 16% (33/202) had IEM by manometric criteria. Of IEM patients, 55% (18/33) had an abnormal videoesophagram, while in 45% (15/33) this test was read as normal. Only 11% (15/137) of patients with a normal videoesophagram were found to have IEM. Sensitivity of videoesophagram was 54.6%, specificity 72.2%, positive predictive value only 27.7%, and negative predictive value 89.1% in the diagnosis of IEM. CONCLUSIONS: These data show that videoesophagram is relatively insensitive in detecting patients with IEM and should not be considered a valid diagnostic test for this disorder. We conclude that esophageal manometry is an indispensable diagnostic modality in the workup of a patient with suspected of IEM.

Adolescent↗
PubMed2003

Redefining gastroesophageal reflux (GER).

BACKGROUND: The detection of gastroesophageal reflux (GER) has to date been limited to acid exposure observed on 24-h pH monitoring. It is clear, however that nonacid reflux can be a significant clinical problem. Recently, as impedance technology with the capacity to detect all types of reflux (acid, nonacid, liquid, mixed, and air) has been developed. METHODS: Seventeen asymptomatic healthy volunteers underwent combined 24-h pH and impedance testing. In all patients, pH was measured at 5 cm above the lower esophageal sphincter (LES), and simultaneous impedance changes were recorded at 3, 5, 7, 9, 15, and 17 cm above the LES. Refluxes were classified as acid (drop in pH <4 for >5 sec), Nonacid, short acid, or nonacid delta based on chemical properties; they were further classified as liquid, mixed, or gas based on the physical refluxate detected by impedance changes. The height of the reflux entering the esophagus was classified as distal (<5 cm), intermediate (5-9 cm), or proximal (9-17 cm). RESULTS: A total of 868 reflux events were characterized. Fifty-nine percent of them were not conventional acid reflux and could only be detected by impedance changes. Less than 2% of the events that were detected by a fall in pH to <4 were not detected by impedance changes. Pure liquid reflux was seen in 35.4%, a mixed pattern in 36.3%, and a gas reflux in 26.7%. Liquid was confined to the distal esophagus in 30%; it reached the midesophagus in 58% and the proximal esophagus in 11%. CONCLUSIONS: Over half of GER events are not detected by pH studies. Liquid reflux reaches the mid and proximal esophagus 69% of the time and gas nearly always does (92%). The additional information provided by impedance technology is likely to have a major impact on the understanding and clinical management of patients with gastroesophageal reflux disease (GERD).

Adult↗
PubMed2001

Cloning and characterization of two guide RNA-binding proteins from mitochondria of Crithidia fasciculata: gBP27, a novel protein, and gBP29, the orthologue of Trypanosoma brucei gBP21.

In kinetoplastid protozoa, mitochondrial (mt) mRNAs are post-transcriptionally edited by insertion and deletion of uridylate residues, the information being provided by guide (g)RNAs. Currently popular mechanisms for the editing process envisage a series of consecutive 'cut-and-paste' reactions, carried out by a complex RNP machinery. Here we report on the purification, cloning and functional analysis of two gRNA-binding proteins of 28.8 (gBP29) and 26.8 kDa (gBP27) from mitochondria of the insect trypanosome Crithidia fasciculata. gBP29 and gBP27 proved to be similar, Arg + Ala-rich proteins, with pI values of approximately 10.0. gBP27 has no homology to known proteins, but gBP29 is the C.fasciculata orthologue of gBP21 from Trypanosoma brucei, a gRNA-binding protein that associates with active RNA editing complexes. As measured in UV cross-linking assays, His-tagged recombinant gBP29 and gBP27 bind to radiolabelled poly(U) and synthetic gRNAs, while competition experiments suggest a role for the gRNA 3'-(U)-tail in binding to these proteins. Immunoprecipitates of mt extracts generated with antibodies against gBP29 also contained gBP27 and vice versa. The immunoprecipitates further harbored a large proportion of the cellular content of four different gRNAs and of edited and pre-edited NADH dehydrogenase subunit 7 mRNAs, but only small amounts of mt rRNAs. In addition, the bulk of gBP29 and gBP27 co-eluted with gRNAs from gel filtration columns in the high molecular weight range. Together, these results suggest that the proteins are part of a large macromolecular complex(es). We infer that gBP29 and gBP27 are components of the C.fasciculata editing machinery that may interact with gRNAs.

Amino Acid Sequence↗
PubMed2001

Risk factors and the prevalence of trocar site herniation after laparoscopic fundoplication.

BACKGROUND: Although there have been case reports describing trocar site herniation after laparoscopic fundoplication, its overall prevalence and the risk factors for its development are unclear. METHODS: The records of 320 patients undergoing primary laparoscopic fundoplication as treatment for gastroesophageal reflex disease (GERD) or hiatal hernia between 1991 and 1999 were reviewed retrospectively. Placement of the initial supraumbilical trocar was by the open Hassan technique in all patients. RESULTS: Nine patients (five male) with a mean age 54 years (range, 37-75) developed trocar site herniation, for an overall prevalence of 3%. The mean interval between surgery and diagnosis was 12 months (range, 4-21). In all patients, the hernia occurred at the supraumbilical camera port site. Patients with trocar hernias tended to have a higher body mass index (BMI) than those without hernias (mean BMI, 29.4 kg/m2 vs 27.2 kg/m2, p = 0.13). None of the patients developed intestinal obstruction as a consequence of herniation. To date, all but one of the hernias have been repaired. Six of them required the insertion of a prosthetic mesh. CONCLUSIONS: The prevalence of trocar site herniation after laparoscopic fundoplication was minimal at 3%. All hernias occurred at the midline supraumbilical port, the only site where open trocar insertion was employed. As a consequence of these observations, we have developed a new method of open trocar placement. This method utilizes a paramedian skin incision and separate fascial incisions through anterior and posterior rectus sheathes, with retraction of the rectus abdominis muscle laterally.

Abdomen↗
PubMed2001

Surgical treatment and outcomes in carcinoma of the extrahepatic bile ducts: the University of Rochester experience.

HYPOTHESIS: To our knowledge, few individual surgeons and only a handful of institutions have gained a meaningful experience with the treatment of adenocarcinoma of the extrahepatic bile ducts or cholangiocarcinoma. The purpose of this study was to critically evaluate the experience of a single center in the treatment of these tumors. DESIGN: Retrospective cohort study with a median follow-up of 48 months. SETTING: Department of surgery at a university referral center. PATIENTS: Seventy-seven patients with biopsy-confirmed adenocarcinoma of the extrahepatic bile ducts evaluated and treated between January 1980 and February 1998. MAIN OUTCOME MEASURES: Prognostic variables, resectability rates, morbidity, and survival. RESULTS: Thirty-eight male and 39 female patients were studied (median age, 71 years). Twenty-three patients (30%) underwent curative resections, 32 patients (41%) underwent palliative surgery, and 22 patients (29%) received nonoperative therapies. The 30-day perioperative morbidity rate was 18%, and mortality was 6%. Overall median survival was 11 months; 4 months for patients receiving nonoperative therapy; 8 months for patients receiving palliative surgery; and 72 months for curative resection. Five-year survival rates were 23%, 0%, 10%, and 55%, respectively. Curative resection was the only prognostic variable to have a statistically significant effect on survival. CONCLUSIONS: Curative resection could be achieved in approximately one third of patients who had cholangiocarcinoma, and should be the goal of treatment. Survival is significantly improved in those patients who are considered to have resectable tumors and who undergo removal of all gross disease. Palliative surgical treatments also revealed a survival advantage over nonoperative therapies.

Aged↗
PubMed2000

Mitochondrial minicircles in the free-living bodonid Bodo saltans contain two gRNA gene cassettes and are not found in large networks.

In trypanosomatids, the majority of the guide (g) RNAs that provide the information for U-insertion/deletion RNA editing are encoded by minicircles that are catenated into large networks. In contrast, in the distantly related cryptobiid Trypanoplasma borreli, gRNA genes appear to reside in large 180-kb noncatenated DNA circles. To shed light on the evolutionary history and function of the minicircle network, we have analyzed minicircle organization in the free-living bodonid Bodo saltans, which is more closely related to trypanosomatids than T. borreli. We identified 1.4-kb circular DNAs as the B. saltans equivalent of minicircles via sequence analysis of 4 complete minicircles, 14 minicircle fragments, and 14 gRNAs. We show that each minicircle harbors two gRNA gene cassettes of opposite polarity residing in variable regions of about 200 nt in otherwise highly conserved molecules. In the conserved region, B. saltans minicircles contain a putative bent helix sequence and a degenerate dodecamer motif (CSB-3). Electron microscopy, sedimentation, and gel electrophoresis analyses showed no evidence for the existence of large minicircle networks in B. saltans, the large majority of the minicircles being present as circular and linear monomers (85-90%) with small amounts of catenated dimers and trimers. Our results provide the first example of a kinetoplastid species with noncatenated, gRNA gene-containing minicircles, which implies that the creation of minicircles and minicircle networks are separate evolutionary events.

Amino Acid Sequence↗
PubMed2000

Surgery, radiotherapy, and chemotherapy in carcinoma of the esophagus.

Esophageal carcinoma remains a highly lethal disease that has shown a recent profound increase in prevalence and an equally dramatic epidemiologic shift. There is a well recognized causal association between gastroesophageal reflux disease and adenocarcinoma of the esophagus, and the molecular events underlying this progression from mucosal injury, to metaplasia, to dysplasia, to carcinoma are now becoming clear. Current diagnostic modalities and preoperative staging systems all have significant limitations. Fortunately, chemoprevention strategies and the identification of clinically useful molecular biomarkers that may be used to stage disease and select appropriate therapy are on the horizon. The extent of surgical resection for esophageal carcinoma remains an area of great controversy. Disease that is confined to the mucosa is being diagnosed more commonly, and endoscopic ablative techniques have been proposed. To date, however, preoperative discrimination of tumor depth and presence of regional nodal metastases remains inadequate in these very early lesions, and caution is urged before adopting therapies that may compromise cure. For disease penetrating the mucosa, the extent of surgical therapy must be tailored by the objectives of treatment (cure vs palliation) and preoperative stage. Surgical resection is the current standard of care, with combined-modality therapy reserved for prohibitive surgical candidates. No clear survival benefit has been documented for neoadjuvant radiotherapy or chemotherapy alone. The results of preoperative combined-modality therapy, including three prospective, randomized trials, are encouraging but to date have not shown a definite benefit.

Journal Article↗
PubMed1999

Tolerance induction permits the development of graft-versus-host disease: donor-mediated attack following small bowel transplantation in mixed chimeras.

The induction of tolerance to organ allografts would eliminate acute and chronic rejection as well as the need for nonspecific immunosuppression. We have shown that tolerance induced through the creation of mixed allogeneic bone marrow chimeras allows for the long-term engraftment of cardiac and small bowel allografts across strong multiple major histocompatibility barriers. The possibility that tolerance might render the host susceptible to graft-versus-host disease (GVHD) has not been investigated in this or other models of tolerance. To test this possibility chimeras were created by transplantation of T-cell depleted ACI and Lewis bone marrow into lethally irradiated Lewis rats. Chimerism was determined post bone marrow transplant (BMTx) by flow cytometry of lymphocytes from reconstituted animals. ACI/Lew chimeras (ALC), Lewis/ACI F1 (LACF1), and Lewis (LEW) rats all received heterotopic ACI vascularized small bowel grafts. A second group of chimeras received small bowel grafts from ACI rats pretreated with low dose irradiation to eliminate T-cells from the graft. LEW-->LEW small bowel isografts were also performed. Animals were examined for evidence of GVHD by clinical signs and histologic examination of biopsied tissues. GVHD was quantified using the popliteal lymph node enlargement assay. All LACF1 rats developed severe lethal GVHD following ACI small bowel transplant. Bone marrow chimeras, ALC (n = 6), developed fatal GVHD in a similar fashion after receiving a small bowel transplant. LEW-->LEW isografts and chimeras receiving bowel from irradiated ACI rats survived long term without GVHD while ACI-->LEW allogeneic transplants all underwent acute rejection. GVHD or its absence was confirmed histologically. Popliteal lymph node enlargement indices reflected the presence of GVHD in the chimeras (1.87) and LACF1 (5.4) receiving allografts, but not in isografts or chimeras receiving irradiated allogeneic transplants. Analysis of cytokines in the tongues of rats undergoing GVHD showed elaboration of Th1 type proinflammatory cytokines which was not seen in isografted rats or rats receiving preirradiated small bowel. These results demonstrate that tolerance induction through mixed chimerism results in susceptibility to small bowel induced GVHD. Preirradiating the donor bowel prior to SBTx can prevent GVHD.

Animals↗
PubMed1998

RNA editing in the free-living bodonid Bodo saltans.

In parasitic kinetoplastid protozoa, mitochondrial (mt) mRNAs are post-transcriptionally edited by insertion and deletion of uridylate residues, the information being provided by guide (g) RNAs. In order to further explore the role and evolutionary history of this process, we searched for editing in mt RNAs of the free-living bodonid Bodo saltans. We found extensive editing in the transcript for NADH dehydrogenase (ND) subunit 5, which is unedited in trypanosomatids. In contrast, B.saltans cytochrome c oxidase (cox) subunit 2 and maxicircle unidentified reading frame (MURF) 2 RNAs display limited editing in the same regions as their trypanosomatid counterparts. A putative intramolecular cox2 gRNA and the gene for gMURF2-I directing the insertion of only one U in the 5' editing domain of MURF2 RNA, are conserved in B.saltans. This lends (further) evolutionary support to the proposed role of these sequences as gRNAs. Phylogenetic analysis showed that B.saltans is more closely related to trypanosomatids than the cryptobiids Trypanoplasma borreli and Cryptobia helicis, in line with the trypanosomatid-like cox2 and MURF2 RNA editing patterns. Nevertheless, other features like the apparent absence of a catenated mtDNA network, are shared with bodonid and cryptobiid species. ND5 RNA editing may represent yet another example of editing 'on the way out' during kinetoplastid evolution, but in view of the fact that cox2 RNA is unedited in T. borreli and C.helicis, we infer that the editing of this RNA may have arisen relatively recently. Our results provide the first examples of RNA editing in a free-living kinetoplastid, indicating that there is no direct link between U-insertion/deletion editing and a parasitic lifestyle.

Amino Acid Sequence↗
PubMed1998

Tolerance induction by intrathymic inoculation prevents chronic renal allograft rejection.

BACKGROUND: These experiments investigated the ability of the donor-specific unresponsiveness created by the intrathymic inoculation of donor alloantigen to effectively prevent chronic rejection in an established rat model of chronic renal allograft rejection. METHODS: Three study groups were examined: (1) Allograft controls--F-344 rats received a Lewis renal allograft plus 10 days of low-dose cyclosporine (CsA); (2) isograft controls--F-344 rats received an F-344 renal isograft and low-dose CsA; (3) experimental group--F-344 rats received a T-cell depleted syngeneic bone marrow transplant and intrathymic injection of Lewis bone marrow. Twenty-one days after bone marrow transplant, these animals received a Lewis renal allograft. RESULTS: Allograft controls demonstrated severe parenchymal fibrosis; isograft controls and intrathymic (IT) animals failed to develop this lesion. Immunohistochemical analysis revealed increased CD4+ T cells infiltrating the cortex of the allograft controls. Cytokine interferon-gamma and interleukin-2 transcripts were strongly positive in allograft controls and were absent from isograft controls and IT allografts as determined by reverse transcriptase-polymerase chain reaction. Analysis of tolerant grafts by flow microfluorimetry and genomic DNA amplification could not detect chimerism to a level of < 0.1%. CONCLUSION: IT inoculation of donor alloantigen can confer long-term unresponsiveness and prevent the development of the characteristic lesions of chronic rejection.

Animals↗
PubMed1998

A more versatile and reliable method for renal transplantation in the rat.

This study describes the authors' experience with a new method of orthotopic renal transplantation in the rat. This technique combines previously described modifications with the use of the donor inferior vena cava as a conduit to perform an end-to-side venous anastomosis. Survival was 87% and 80% at 3 and 120 days, respectively. Patency was 80% at 120 days, and histologic examination revealed normal renal architecture and parenchyma, with no evidence of ischemic injury. This technique offers a refinement of previous techniques and is reliable, flexible, and can be easily learned by novice microvascular surgeons.

Anastomosis, Surgical↗
PubMed1997

Graft versus host disease in rats made tolerant for organ allografts.

Tolerance for organ allografts would eliminate acute and chronic rejection as well as the need for nonspecific immunosuppression. A potential hazard of tolerance is the susceptibility to graft vs host disease (GVHD) due to unresponsiveness to alloantigen. This study sought to determine if our model of tolerance induction results in susceptibility to GVHD. Chimeras were created by transplantation of T-cell depleted ACI and Lewis bone marrow into lethally irradiated Lewis rats. Chimerism was determined post-BMTx by flow cytometric analysis of recipient spleens for the presence of ACI cells. ACI/Lew chimeras (ALC), animals that reconstituted only with syngeneic (Lewis) marrow (so-called failed chimeras), and ACI/Lew F1 (LACF1) hybrid rats were all given 200 x 10(6) ACI splenocytes i.v. Animals were examined for evidence of GVHD. GVHD was quantified using the popliteal lymph node enlargement assay. All LACF1 (n = 6) rats developed severe lethal GVHD following ACI splenocyte injection. Similarly, ALC (n = 6) developed fatal GVHD. Animals that reconstituted only with syngeneic Lewis marrow (failed chimeras) showed no signs of illness. GVHD was confirmed histologically and immunohistochemically. Failed chimeras receiving ACI splenocyte challenge showed no evidence of GVHD histologically. Popliteal lymph node enlargement indices reflected the presence of GVHD in the chimeras and hybrids but not in the failed chimeras. We conclude that tolerance induction by mixed chimerism results in susceptibility to GVHD if enough donor lymphoid tissue is given to the host at the time of organ transplant. Animals that are not mixed chimeras (failed bone marrow transplant) rejected the allogeneic splenocytes as evidenced by their lack of disease. Tolerance may therefore make the host defenseless against fatal GVHD.

Animals↗
PubMed1996

Induction of specific tolerance through mixed hematopoietic chimerism prevents chronic renal allograft rejection in a rat model.

BACKGROUND: Chronic rejection is the leading cause of late graft loss in kidney transplantation. We tested the ability of mixed hematopoietic chimerism to prevent chronic renal allograft rejection in an established rat model and described possible mechanisms responsible for this tolerance. METHODS: Mixed hematopoietic chimerism was established in lethally irradiated F-344 rats by reconstitution with Lewis bone marrow. Four groups (n = 5 each) received orthotopic kidney transplants: (1) allograft controls, (2) isograft controls, (3) experimental chimeras, and (4) specificity control. After 120 days kidney grafts were examined histologically, immunohistochemically, and for cytokine interferon-gamma, interleukin-2 (IL-2), IL-4, and IL-10 gene transcripts by means of reverse transcriptase polymerase chain reaction techniques. RESULTS: Allograft control group exhibited severe parenchymal fibrosis; isograft control and chimera groups failed to develop this lesion. Immunohistochemical analysis revealed increased CD8+ lymphocytes and ED-1+ monocyte-macrophages infiltrating the tubulointerstitium of control allografts. Interferon-gamma and IL-2 were absent in isografts. IL-4 was absent and IL-10 was positive in all grafts. Chimeras promptly rejected third-party allografts. CONCLUSIONS: Induction of specific tolerance through mixed hematopoietic chimerism prevents chronic renal allograft rejection. These results support the hypothesis of an immunologic basis of chronic rejection and advance previous observations that the induction of specific tolerance enables long-term solid organ transplantation without the use of immunosuppression.

Animals↗