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Biomedical subjects

J W Jones

Publications and source records attributed to J W Jones.

At least 109 records · Page 6Linked to original sources

Diagnosis and operation for anomalous circumflex coronary artery.

BACKGROUND: Origin of the left circumflex coronary artery from the right sinus of Valsalva is the most common anatomic variation of the coronary artery circulation. However, there are few reports about the operative approach to this anomalous vessel. METHODS: Forty patients having this anomaly were identified from 10,216 adult cardiac catheterization procedures. Forty percent of the anomalous circumflex coronary arteries (ACCAs) had critical atherosclerotic lesions. Eighty cases needed bypass grafting. RESULTS: For diagnosis of ACCA, the aortic root sign was positive in 94.9% of the diagnosed patients and the nonperfused myocardium sign was found in 92.5%. Eighty percent of ACCAs were larger than 2 mm in radiographic diameter before their passage into the atrioventricular groove. However, after emerging from the atrioventricular groove, 70% measured less than 1.5 mm. Consequently, a technique was developed to bypass the proximal ACCA and was used in 2 cases. Six other patients with more distal disease and larger vessels underwent conventional bypass grafting. CONCLUSIONS: The aortic root sign and nonperfused myocardium are useful in diagnosing ACCA. The ACCA is usually too small for use of the conventional graft technique. Therefore, a technique was developed to graft more proximally and was applied successfully in 2 cases.

Adult↗

Improved survival with multiple left-sided bilateral internal thoracic artery grafts.

BACKGROUND: Although conceptually sound, the use of multiple internal thoracic artery (ITA) bypass grafts to improve long-term clinical results remains controversial. This operation typically involves grafting the left ITA to the anterior descending artery and the right ITA to the right coronary artery. Past clinical studies of bilateral ITA operations have not examined comparative results associated with which coronary arteries received the ITA bypass grafts. Because grafting a superior conduit to an artery of lesser physiologic importance might reduce the clinical benefits, we compared the outcomes of patients receiving different configurations of bilateral ITA operations. METHODS: The study group was 498 consecutive bilateral ITA operations, constituting the 10-year experience of a single surgeon. Follow-up averaged 7.1 years (mode 7.3 years), and was 94.2% complete. These patients were divided into two groups, 311 patients (group I) who underwent the traditional operation (left ITA to the left anterior descending artery, right ITA to the right coronary artery), and 187 patients (group II) who received revascularization of branches of the left coronary artery (left ITA to the circumflex system and right ITA to the left anterior descending artery). RESULTS: The study groups were similar in age, severity of disease, number of bypassed arteries, ejection fraction, diabetes, hypertension, and duration of operation. There were more male patients in group II (91.4% versus 82.3%). A multivariate analysis showed that the location of ITA bypass grafts influenced survival independent of gender (p = 0.0288). Operative morbidity and mortality were similar between groups. Ninety-three patients had repeat angiography with equivalent patency rates of the ITA conduits (91.7% versus 89.6%; p = 0.67). The Kaplan-Meier actuarial survival estimate demonstrated a significant improvement in survival of patients in group II who received both ITA bypass grafts to left-sided arteries (p = 0.021), with the survival curves diverging at 6 years. More patients in group II were in New York Heart Association class I or II, but the difference was not statistically significant (94.6% versus 91.6%). Only 2 patients required reoperation. CONCLUSIONS: It appears that maximum long-term benefit from bilateral ITA operations is achieved by grafting the ITA conduits to coronary arteries that supply more left ventricular muscle.

Coronary Angiography↗

Effect of recombinant human erythropoietin on transfusion risk in coronary bypass patients.

BACKGROUND: Patients having a cardiac operation frequently require allogeneic blood transfusions despite surgical blood-conservation techniques. Recombinant human erythropoietin (Epoetin alfa) may augment this conservation by stimulating erythropoiesis. The safety and efficacy of perioperative use of Epoetin alfa to reduce the need of allogeneic transfusion was studied. METHODS: A multicenter double-blind, placebo-controlled, parallel-group study involved 182 patients having coronary artery bypass grafting and randomized to receive Epoetin alfa (300 or 150 IU/kg) or placebo subcutaneously for 5 days before, on the day of, and for 2 days after operation. RESULTS: Perioperative Epoetin alfa resulted in greater increases in baseline to preoperative hemoglobin levels and hematocrit (300 IU/kg) and in presurgery to postsurgical day 1 reticulocyte counts versus placebo (p < or = 0.05). However, there was no significant difference in transfusion requirements. Incidences of adverse events were similar in all study groups. CONCLUSIONS: Lower incidences of allogeneic blood exposure were observed in both Epoetin alfa-treated groups; however, the differences between all treatment groups were not significant. This was probably due to the relatively short 5-day preoperative course of Epoetin alfa therapy. There were no significant differences between the three groups relative to safety. Epoetin alfa was well tolerated in this population.

Antibodies↗

Clinical variables influencing the appearance of right bundle branch block after cardiac surgery.

Right bundle branch block following coronary surgery is a common occurrence. Among 759 coronary surgery cases, 104 patients (13.7%) had a new right bundle branch block. Of these right bundle branch blocks, 62 were transient, and 42 (40.4%) were permanent. The large number of bypasses (3.20 versus 2.75, P = 0.0001) and stenosis of the right coronary artery (81.7% versus 66.5%, P = 0.003) was strongly associated with a new right bundle branch block. In the analysis of the permanent right bundle branch block, blood cardioplegia prevented the block from becoming permanent (35.7% versus 75.8%, P = 0.0001). Therefore, it is concluded that perioperative right bundle branch block occurs predominantly in patients who have a critical stenosis in an artery which supplies the conduction system and in those undergoing more extensive procedures. In addition, blood cardioplegia affects the conduction system less severely than does crystalloid cardioplegia.

Adult↗

Molecular basis of the D variant phenotypes DNU and DII allows localization of critical amino acids required for expression of Rh D epitopes epD3, 4 and 9 to the sixth external domain of the Rh D protein.

The discovery of Rh partial D variant red cells by discrepant reactions with different monoclonal anti-D has demonstrated the range of Rh D epitopes that have arisen due to alterations in Rh D protein structure. There are two current classification systems, one which uses a nine epitope model (epD1-epD9) whereas a more recent model proposes 30 different epitopes. We describe here the molecular basis of two D variants which lack epD4 and epD9 namely the DNU and D(II) phenotypes. These would have both been originally classified as D(II) phenotype individuals, but we have revealed subtle differences in the serological profile of these erythrocytes. Such a differential reactivity and determination of the molecular bases of these phenotypes allows us to predict critical amino acids for epD3, epD4 and epD9 expression. The DNU phenotype arises from a single point mutation in the RHD gene resulting in a single amino acid change (Gly353Arg). Sequence analysis of exon 7 of the RHD gene derived from the D(II) propositus indicates that there is a single point mutation in this exon resulting in a single amino acid change (Ala354Asp). It is likely that this point mutation gives rise to the D(II) phenotype. Both mutations result in the change to Rh D-specific residues. Our results indicate that the following amino acids are crucial for epD3a (Asp350), epD3b (Asp350 + Gly353), epD4a (Gly353 + Ala354), epD4b (Ala354), epD9a (Asp350 + Gly353 + Ala354) and epD9b (Asp350 + Ala354) expression. All of these amino acids reside on the predicted sixth external domain of the Rh D protein, so it is possible that epD3, 4 and 9 are continuous epitopes.

Amino Acids↗

The serological profile and molecular basis of a new partial D phenotype, DHR.

BACKGROUND AND OBJECTIVES: The Rh D antigen comprises a mosaic of at least 30 epitopes expressed on a 30-kD non-glycosylated Rh D polypeptide. The equivalent Rh CeEe polypeptide expressing the Rh C/c and E/e antigens differs in only 36 of the 417 amino acid residues. Partial D individuals have been described who fail to express a number of D epitopes. MATERIALS AND METHODS: Serologic methods were applied with monoclonal anti-D to map epitopes on the red cells of a proposita aberrant D typing. Polymerase chain reaction (PCR) and DNA sequencing were also done. RESULTS: DNA sequence analysis derived by RT-PCR using total RNA isolated from peripheral blood of this person suggests two mechanisms for the genetic basis of this variants: one here gene conversion events result in the replacement of RHD gene exons with the equivalent RHCE exons; the second where point mutation in the RHD gene generates an amino acid substitution in the Rh D protein. CONCLUSIONS: We report here a new partial D, DHR, where a single point mutation (G to A at nucleotide 686) in exon 5 of the RHD gene results in a conservative amino acid substitution (Arg229Lys), in the predicted Rh D protein. This residue is localised on the fourth predicted exofacial loop of the Rh D polypeptide as determined by hydropathy analysis. This substitution results in the lack of epD 1, 2, 12 and 20 (30 epitope model) and indicates the involvement of loop 4, and in particular the requirement of Arg229, in the expression of these epitopes.

Amino Acid Substitution↗

Adjunctive measures in microvascular surgery.

Consistently good results following free-tissue transfers require not only basic skills in small vessel anastomosis, but also the implementation of numerous adjunctive measures. The pioneers in microsurgery have shared many of their hard-learned lessons and clinical nuggets through texts, papers, and seminars. This article presents an assemblage of adjunctive measures of proven utility.

Humans↗

Suitability and durability of multiple internal thoracic artery coronary artery bypasses.

OBJECTIVE: The authors evaluate operative and extended outcomes of coronary artery bypass surgery using the bilateral internal thoracic arteries (ITAs) as bypass grafts. The authors conclude that the procedure is viable and of long-term benefit to most patients. SUMMARY BACKGROUND DATA: Multiple ITA grafting was met with early enthusiasm by the surgical profession, but skepticism and controversy arose with reports of increased operative morbidity, insufficient graft blood flow, a high incidence of failure of the right ITA, and uncertainty about durability and long-term benefits. METHODS: To assess the actual incidence and impact of these complications and long-term results, the authors prospectively studied 500 consecutive patients with multiple ITA bypasses, constituting the closely observed and carefully documented experience of one surgeon over an 11-year period. RESULTS: Operative mortality in the series of 500 patients was 1.8%, perioperative myocardial infarction (new Q wave) rate was 0.6%, and deep sternal wound infection occurred in 1%. Six patients (1.2%) had strokes, and nine patients (1.8%) were returned to the operating room to control bleeding. One hundred ninety-eight patients who had abnormal stress test results before surgery were retested within 3 months of surgery. Ninety-four percent of these were normal, 3% were nondiagnostic, and 3% were abnormal. After a mean follow-up of 7.1 years (mode, 7.2 years), 87.5% of patients in the sample were alive, and 93.2% of this group have experienced continuing good clinical results (New York Heart Association class I or II). Eighty-nine patients who underwent an angiogram had 90.8% patency rates of ITA bypasses and 84.5% patency of vein grafts. Only two patients required repeat operations. CONCLUSIONS: The operative results did not support the contention that the coronary artery bypass using ITA procedure produces higher than acceptable mortality and morbidity rates. Multiple ITA bypasses can be performed without excessive morbidity, with low reoperation rates and long-term outcomes that should encourage skeptics to reconsider the procedure's clinical value.

Aged↗

Cerebral oxygenation during warming after cardiopulmonary bypass.

OBJECTIVES: To evaluate jugular venous oxygen saturation (SjVO2), measured with a fiberoptic oximetry catheter, and brain tissue oxygen saturation, measured by near-infrared spectroscopy (NIRSO2), as monitors of cerebral oxygenation during cardiopulmonary bypass surgery. DESIGN: Prospective, clinical study. SETTING: Operating room of a Veterans Administration Hospital. PATIENTS: Nineteen patients undergoing moderate hypothermic cardiopulmonary bypass surgery. INTERVENTIONS: SjvO2 and NIRSO2 were monitored in the patients during the surgical procedure. MEASUREMENTS AND MAIN RESULTS: Moderate hypothermic cardiopulmonary bypass surgery had two distinct cerebral hemodynamic phases. While the patients were hypothermic, SjvO2 averaged 80 +/- 7% and none of the patients had an increase in cerebral lactate production. During the rewarming period, however, reductions in SjvO2 to < 50% occurred in 16 (84%) patients and increased cerebral anaerobic metabolism developed in 11 (58%) patients. SjvO2 during rewarming was dependent on mean arterial pressure, with 60 mm Hg appearing to be a critical value. Two other factors appeared to also contribute to the jugular desaturation, a low hematocrit and a rapid warming time. The SjvO2 catheter had excellent performance during the surgery. The average difference between paired measurements of SjvO2 by the catheter and in blood samples was -0.4 +/- 4.25%, and the correlation between the two measurements was highly significant (r2 = .93; p < .001). The NIRSO2 trended with the SjvO2 in most patients (r2 = .63; p < .001). CONCLUSIONS: The study confirms other studies showing that jugular venous desaturation can occur during rewarming after cardiopulmonary bypass surgery. Presently, SjvO2 appears to be a better monitor of cerebral oxygenation than NIRSO2. However, NIRSO2 has promise as a noninvasive monitor of cerebral oxygenation if future developments allow more quantitative measurements of oxygen saturation.

Aged↗

Identifying genetic changes associated with tumor progression in squamous cell carcinoma.

Tumor behavior is the result of specific genetic changes that alter gene expression. From our cytogenetic studies chromosome 18 loss emerged as a common genetic change in squamous carcinoma cell lines. In this report we summarize data that link loss of 18 to tumor progression and reduced survival, indicating that one or more tumor suppressor gene(s) are located on this chromosome. Tumors grown in vitro were karyotyped either as short-term or permanent cultures. Loss of chromosome 18 was measured by karyotype, decreased frequency of heterozygosity at the DCC locus, and loss of heterozygosity (LOH) for microsatellite repeat polymorphisms (MSRP). Loss of any part of chromosome 18 was observed in approximately 63% of cultured tumors. Primary and secondary tumors from the same individuals sometimes differed in loss of 18 indicating that this genetic change is associated with tumor progression. Heterozygosity for DCC was present in only 3/19 cultured SCC (16%), compared with 68% (11/16) of blood samples from unrelated donors, which is consistent with LOH in roughly one half of the cases. Of 4 informative cases with normal and tumor tissue, LOH was observed in 2. Microsatellite analysis also shows loss of 18q in 55% of fresh tumors. Analysis of tumor tissue and cell lines from the same patient gave identical results. There was an excess of deaths from cancer in the group with 18 loss (20/25) when compared with the group without (5/15). Loss of chromosome 18 appears to be a marker of tumor progression in SCC. It is likely that mutation affecting DCC or another gene on 18 affects tumor growth or spread, leading to more rapid progression and reduced survival.

Carcinoma, Squamous Cell↗

Immunochemical analysis of the human erythrocyte Rh polypeptides.

We have used rabbit polyclonal antisera raised against synthetic peptides complementary to different domains of the Rh polypeptides and Rh glycoprotein to examine the topography and organization of these proteins in the human erythrocyte membrane. Previously unrecognized exofacial protease sites have been identified on Rh CcEe, D proteins, and Rh glycoprotein. The Rh D protein has two specific bromelain cleavage sites located within the first and sixth predicted external domains, with the site of cleavage localized in the sixth domain to lie between residues 353 and 354. All Rh polypeptide species were found to be susceptible to cleavage with trypsin and subtilisin within the first external domain of these proteins. The Rh glycoprotein has two bromelain cleavage sites within the first external domain. These flank the single N-glycosylation site (Asn37), with the cleavage site toward the C-terminal side of this residue being between residues 39 and 40. Bromelain treatment was found to deglycosylate the Rh glycoprotein. Immunoprecipitation experiments have revealed that anti-C, -c,E, -e, and -D immune complexes are reactive with antisera raised against the fourth predicted external loop of the Rh proteins and the C-terminal domain. These data indicate that the hypothesis that suggests Rh C/c antigens are expressed on truncated Rh polypeptides by a mechanism of alternate splicing is incorrect and support the hypothesis that Rh Cc and Ee antigens are expressed on a single polypeptide chain.

Amino Acid Sequence↗

A tonsillolith.

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Aged↗

Myocardial revascularization in a hemophiliac.

The case of a mild hemophiliac who underwent a successful and uncomplicated myocardial revascularization is presented. The procedures was safely performed while the patient was receiving factor VIIIC.

Angina Pectoris↗

A structural model for 30 Rh D epitopes based on serological and DNA sequence data from partial D phenotypes.

Both cDNA RHD sequences and reactivity with monoclonal anti-D have been reported in a number of partial D phenotypes, where parts (some epitopes) of the normal D antigen are missing, and anti-D of restricted specificity may be made in response to challenge with normal D positive blood. This paper analyses these reports together and proposes a model for the structure which comprise the epitopes of the Rh D antigen. Some epitopes are proposed to be comprised of continuous peptide sequence within one extracellular loop, whereas others require interactions between two or the extracellular peptide loops.

DNA↗

Quantitation of Rh D antigen sites on weak D and D variant red cells by flow cytometry.

Information on the number of D sites on weak D (Du) and D variant cells is limited and incomplete. The aim of this study was to use a simple non-isotopic technique utilising a combination of flow cytometry and ELISA to quantitate the number of D sites on an extensive range of these cells. Five human monoclonal IgG anti-D (BRAD-7 (JAC10), BRAD-5, 2B6, BRAD-3, H27) and one affinity-purified polyclonal IgG anti-D were each used at a saturating concentration of 20 micrograms/ml. In general, BRAD-3, BRAD-5 and 2B6 gave the highest number of D sites per cell (SPC), H27 and the polyclonal anti-D were slightly lower, while BRAD-7 gave the lowest SPC with all D-positive cells tested except DFR. Interestingly, BRAD-7 gave the highest SPC with DFR cells. Rh D antigen density for R2R2 cells was approximately double that seen with either R2r or Rzero (presumed R0r) cells. R1R1 cells gave only moderately higher SPC than R1r cells.Higher SPC were obtained with the R1 haplotype if the CW antigen was present. Weak D, Va and VI cells of the R1 haplotype had higher SPC than those of the Rzero or R2 haplotypes. The majority of D variant cells were found to have lower SPC than normal cells, and for polyclonal anti-D, which was the only anti-D to react with all D variants, SPC decreased in the order IIIc > IIIa > HMii > IVa > Va > DFR > DBT > IVb > VII > II > HMi > VI. The number of molecules of IgG anti-D bound to D variant cells varied by up to 10 times with reactive monoclonal antibodies. The highest SPC on weak D and D variant cells were obtained with BRAD-7 (DFR, 9,500), BRAD-3 (Va, 12,500), BRAD-5 (II, 5,500; VII, 5,300; weak D, 1,300), H27 (III, 24,000; VI, 2,900; HMi, 3,000; HMii, 16,800) and polyclonal anti-D (IVa, 9,300; IVb, 4,000; DBT, 4,300).

Antibodies, Monoclonal↗