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K McManus

Publications and source records attributed to K McManus.

At least 19 recordsLinked to original sources

Effect of medroxyprogesterone pretreatment on pentagastrin-induced panic symptoms in females with panic disorder.

Clinical observation, as well as epidemiological and research data, suggest that female gonadal hormones influence the course of panic disorder (PD). Panicogenic agents such as pentagastrin are useful tools with which to study the pathophysiology of panic attacks. Nine women with PD were randomly assigned to receive, in a crossover design, a 3-day pretreatment with medroxyprogesterone acetate (MP) prior to an injection of pentagastrin, and a 3-day pretreatment with a placebo prior to another injection of pentagastrin. The panic response and the anxiety response to pentagastrin were decreased after MP pretreatment. These preliminary results support the use of laboratory models for investigations of the interactions between progestins and anxiety.

Adult↗

Effect of ethinyl estradiol on the panic response to the panicogenic agent pentagastrin.

BACKGROUND: Panic disorder (PD) symptomatology has been reported to be altered by hormonal events or treatments which affect estrogen levels. Coryell et al. [Arch. Gen. Psychiatry, 39 (1982) 701-703; Am. J. Psychiatry, 143 (1986) 508-510] have suggested that the increased cardiovascular risk associated with PD is significantly greater in males, alluding to a potential cardioprotective effect of female hormones in the context of panic attacks. In the present study, we were, therefore, interested in elucidating the role of estrogen in modulating the behavioural and cardiovascular responses induced by the panicogenic agent pentagastrin, a cholecystokinin-B (CCK(B)) receptor agonist. METHODS: A double-blind cross-over placebo-controlled design with randomization of the order of a 3-day pretreatment of ethinyl estradiol (EE) (50 microg/day) or placebo was used to assess the effect of a 30-microg i.v. bolus injection of pentagastrin on panic symptom intensity and on increases in heart rate (DeltaHR), systolic (DeltaSBP) and diastolic (DeltaDBP) blood pressure following each pretreatment. Subjects were 9 male healthy controls and 11 male PD patients. RESULTS: EE pretreatment did not significantly reduce the pentagastrin-induced panic symptom scale (PSS) scores and had no effect on DeltaDBP or DeltaSBP. EE did, however, attenuate the pentagastrin-induced increase in HR in both PD patients and healthy controls. LIMITATIONS: Only male subjects were included in the present study; however, we are currently investigating the influence of female gonadal hormones on the panic response to pentagastrin in female PD patients and healthy controls. CONCLUSION: Our results suggest that estrogens may display cardioprotective effects in the context of panic attacks.

Adult↗

A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults.

CONTEXT: Long-term success in weight loss with dietary treatment has been elusive. OBJECTIVE: To evaluate a diet moderate in fat based on the Mediterranean diet compared to a standard low-fat diet for weight loss when both were controlled for energy. DESIGN: A randomized, prospective 18 month trial in a free-living population. PATIENTS: A total of 101 overweight men and women (26.5-46 kg/m(2)). INTERVENTION: (1) Moderate-fat diet (35% of energy); (2) low-fat diet (20% of energy). MAIN OUTCOME MEASUREMENTS: Change in body weight. RESULTS: After 18 months, 31/50 subjects in the moderate-fat group, and 30/51 in the low fat group were available for measurements. In the moderate-fat group, there were mean decreases in body weight of 4.1 kg, body mass index of 1.6 kg/m(2), and waist circumference of 6.9 cm, compared to increases in the low-fat group of 2.9 kg, 1.4 kg/m(2) and 2.6 cm, respectively; P < or = 0.001 between the groups. The difference in weight change between the groups was 7.0 kg. (95% CI 5.3, 8.7). Only 20% (10/51) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54% (27/50) in the moderate-fat group, (P<0.002). The moderate-fat diet group was continued for an additional year. The mean weight loss after 30 months compared to baseline was 3.5 kg (n = 19, P = 0.03). CONCLUSIONS: A moderate-fat, Mediterranean-style diet, controlled in energy, offers an alternative to a low-fat diet with superior long-term participation and adherence, with consequent improvements in weight loss.

Adult↗

Self-expanding oesophageal stents: strategies for re-intervention.

BACKGROUND AND STUDY AIMS: Self-expanding metal stents have become accepted palliation for inoperable malignant oesophageal obstruction, the cost of the devices being offset against the ease of insertion and the reduced complication rate. However, re-intervention is often required for obstruction, malposition, migration and tumour progression. The marginal cost of re-stenting is generally higher than other modalities. This study aims to determine the rate of re-intervention and the effectiveness of the various intervention modalities. PATIENTS AND METHODS: A population of 165 patients, treated in a tertiary referral oesophageal centre, (132 with oesophageal cancer, 31 with mediastinal metastases from other tumours, two with benign conditions) whose initial stent placement was performed between January 1994 and December 1998 was followed-up through July 1999 or till death. RESULTS: A total of 75 re-interventions were required in 44 patients and were successful in 51 (68%). Rigid oesophagoscopy and removal of food bolus was successful in three out of three, dilation in one of 11, rigid oesophagoscopy and physical debridement in 12 of 17 and laser debridement in 12 of 20. Re-stenting was the primary re-intervention in 10 cases and was ultimately necessary in 14 patients (with 11 self-expanding metal stents, three Celestin) who had previously undergone other forms of re-intervention. It was not successful in one case. The median survival following first re-intervention was 9.8 weeks (compared with 14.3 weeks for initial stenting) and was longer in those receiving radiotherapy (23.6 weeks) or chemotherapy (14.4 weeks). CONCLUSIONS: While repeated stenting is usually successful, debridement and laser vaporization are viable alternatives for proximal tumour overgrowth or ingrowth in the upper or middle third of the oesophagus. Distal tumour growth or ingrowth at the oesophagogastric junction are best treated with a second stent. Repeated treatment is justified, as survival following first re-intervention is comparable to that after initial stenting, particularly in those patients who are able to undergo chemotherapy or radiotherapy.

Equipment Design↗

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of thymus.

This report describes a low-grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT) involving the thymus of a 63-year-old woman with features suggestive of a connective tissue disease. Sections of the thymic lesion and of a lung biopsy performed at the same operation were examined histologically and by immunohistochemistry using the monoclonal antibodies CD45, CD20, CD79a, CD3, CD45RO, and AE1/AE3. Polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement was also performed. The dense infiltrate of small lymphoid cells intimately admixed with ramifying epithelial elements, some of which had undergone cystic change, closely resembled a thymoma. The lymphoid infiltrate comprised centrocyte-like cells, small lymphocytes, plasma cells, and blasts. Most of the lymphoid cells were immunoreactive with the B-cell markers CD20 and CD79a, and PCR showed clonal immunoglobulin heavy chain gene rearrangement. The lung biopsy showed dense infiltration by small lymphoid cells, morphologically suggestive of lymphoid interstitial pneumonia. However, PCR showed a weak band in the amplification for immunoglobulin heavy chain gene rearrangement, identical to that within the thymus and suggesting either recirculation of cells to accumulated MALT or subhistological lymphoma. MALT lymphoma may rarely involve the thymus, and pathologists should be aware of this to avoid misdiagnosis as a thymoma. Immunohistochemical and/or molecular studies are of value in this regard. MALT lymphomas of the thymus, common with those arising in other organs, may develop in the setting of a connective tissue disease.

Biopsy↗

Amino acid substitutions in human erythroid protein band 3 account for the low-incidence antigens NFLD and BOW.

BACKGROUND: The low-incidence red cell antigens NFLD (700.37) and BOW (700.46) were first described in 1984 and 1988, respectively. Recent investigations showed that antigens of the Diego blood group system (including a number of low-incidence antigens) are coded by SLC4A1 (solute carrier family 4, anion exchanger member 1 gene). Among these newly characterized Diego system antigens is Wu (designated DI9). Because a serologic relationship among Wu, NFLD, and BOW has been established, a series of genetic and molecular investigations of SLC4A1 in relation to NFLD and BOW were undertaken. STUDY DESIGN AND METHODS: By the use of exon-specific primers, single-strand conformational polymorphism (SSCP) analysis of SLC4A1 was performed on DNA isolated from an NFLD+ person from Japan, from the members of a Canadian kindred segregating for NFLD, and from two unrelated BOW+ persons. Exons displaying SSCPs were subjected to genetic linkage analysis (for NFLD only) and DNA sequencing. RESULTS: SSCPs in DNA amplified from exons 12 and 14 of SLC4A1 were observed for all NFLD+ subjects. Linkage between each of these polymorphisms and NFLD was established with peak lods = 4.82 at theta = 0.00 for combined paternal and maternal meiosis. DNA sequencing of exons 12 and 14 of SLC4A1 from NFLD+ persons identified A-->T and C-->G mutations that underlie Glu429Asp and Pro561Ala substitutions in human erythroid band 3 protein (band 3). DNA from the two unrelated BOW+ persons only exhibited an SSCP in exon 14 of SLC4A1. Subsequent DNA sequencing revealed a C-->T mutation that accounts for a Pro561Ser substitution in band 3. CONCLUSION: SLC4A1 codes for the low-incidence red cell antigens NFLD and BOW. In light of these findings, both antigens have been assigned to the Diego blood group system.

Amino Acid Substitution↗

An amino acid substitution in the putative second extracellular loop of RBC band 3 accounts for the Froese blood group polymorphism.

BACKGROUND: The low incidence RBC antigen Fr(a) has been excluded from 17 of the 25 established blood group systems. Previous genetic analysis assigned the gene controlling Fr(a) expression to the same chromosomal region as the solute carrier family 4, anion exchanger member 1 gene (SLC4A1). Because SLC4A1 encodes RBC band 3 and controls the expression of Diego blood group system antigens, the possible relationship of Fr(a) to the Diego blood group system was investigated by molecular analysis of SLC4A1. STUDY DESIGN AND METHODS: Blood samples were obtained from the members of two unrelated Mennonite kindreds segregating for Fr(a). DNA was extracted, amplified by PCR using intronic primer sets flanking exons 11-20 of SLC4A1, and screened by single-strand conformation polymorphism (SSCP) analysis. Those exons displaying SSCPs were subjected to DNA sequence analysis. RESULTS: An exon 13 SSCP mobility shift was observed in the DNA from all Fr(a+) persons that was not seen in the DNA from Fr(a-) family members or control subjects. Linkage between the exon 13 SSCP and FR:(a) was established, with peak lods = 3.62 at theta = 0.00 for combined paternal and maternal meioses. DNA sequencing revealed a GAG --> AAG mutation that underlies a Glu480Lys substitution in RBC band 3. CONCLUSIONS: A point mutation in exon 13 of SLC4A1 accounting for a Glu480Lys substitution in band 3 controls Fr(a) expression. On the basis of these our results, the International Society of Blood Transfusion Working Party on Terminology for Red Cell Surface Antigens has assigned Fr(a) to the Diego blood group system, with the designation DI20.

Amino Acid Substitution↗

Distinctive Swann blood group genotypes: molecular investigations.

BACKGROUND AND OBJECTIVES: Phenotypically, Sw(a+) erythrocytes have been classified as either 700:4,41 or 700:4,-41. Since anti-700.4, in particular, and sometimes anti-700.41 are contained in reagents defining other low-incidence antigens that are members of the Diego blood group system, we undertook the current investigation in an attempt to establish whether or not Swann antigens are also Diego system members. MATERIALS AND METHODS: DNA from the members of three unrelated kindreds whose red cells type as Sw(a+) was isolated and analyzed for variation in SLC4A1 (solute carrier family, anion exchanger member 1 gene) by single-strand conformational polymorphism (SSCP) and DNA sequence analyses. RESULTS: Polymerase chain reaction-amplified exon 16 SLC4A1 products from the DNA of all Sw(a+) individuals displayed a mobility shift by SSCP. A similar mobility shift was not observed in the DNA from Sw(a-) family members or in the amplified DNA from control individuals. DNA sequencing revealed different mutations, CGG-->CAG and CGG-->TGG, that result in Arg646Gln and Arg646Trp substitutions in erythroid protein band 3, respectively. CONCLUSION: Through genotypic analyses, we have characterized two point mutations related to the Swann blood group. The possible relationship between the resultant amino acid substitutions and the expression of Swann antigens has been discussed.

Amino Acid Substitution↗

Total thoracic oesophagectomy for oesophageal carcinoma: has it been worth it?

OBJECTIVE: Anastomotic recurrence is a major cause of late mortality following oesophago-gastrectomy (OG) for carcinoma of the oesophagus and oesophago-gastric junction using either the Ivor Lewis or left thoraco-abdominal approach with intra-thoracic anastomosis. The aim of this study was to determine whether the more extensive total thoracic oesophagectomy (TTO) with cervical anastomosis would reduce the anastomotic recurrence rate while maintaining acceptable operative morbidity and mortality. METHODS: From January 1988 to December 1996, 108 total thoracic oesophagectomies and 66 oesophago-gastrectomies were performed with curative intent in 174 patients (125 males, mean age 62.4 years) with carcinoma (squamous cell carcinoma in 34 and adenocarcinoma in 140) of the middle (31 patients) and lower (44 patients) oesophagus and oesophago-gastric junction (99 patients). RESULTS: Minor complications occurred in 37 (34%) total thoracic oesophagectomy and 18 (27%) oesophago-gastrectomy patients, major complications in 15 (14%) and 5 (8%) and peri-operative death in 5 (4.6%) and 7 (11%) patients, respectively. Anastomotic leakage occurred in 10 (9%) total thoracic oesophagectomy and 5 (8%) oesophago-gastrectomy patients, and was fatal in 1 (1%) and 4 (6%). There was no incidence of tumour at or within 5 mm of the proximal limit in the total thoracic oesophagectomy group and this was reflected in the complete absence of anastomotic recurrence. In the oesophago-gastrectomy group there was a positive proximal resection margin in 13 (20%) and 13 anastomotic recurrences (22% of peri-operative survivors). The 5-year survival (including operative mortality) was 29% for total thoracic oesophagectomy compared with 21% for the other techniques (P = 0.028 log rank test). Median survival was 25.2 months after total thoracic oesophagectomy and 15.8 after oesophago-gastrectomy. CONCLUSIONS: Total thoracic oesophagectomy can be performed in oesophageal cancer patients with comparable morbidity to that of lesser resections. Incomplete proximal resection and anastomotic recurrence did not occur in this series of 108 total thoracic oesophagectomies and this is reflected in an increased medium term survival. The improved survival is most apparent for tumours of the oesophago-gastric junction.

Adenocarcinoma↗

Effect of thoracotomy and lung resection on exercise capacity in patients with lung cancer.

BACKGROUND: Resection is the treatment of choice for lung cancer, but may cause impaired cardiopulmonary function with an adverse effect on quality of life. Few studies have considered the effects of thoracotomy alone on lung function, and whether the operation itself can impair subsequent exercise capacity. METHODS: Patients being considered for lung resection (n = 106) underwent full static and dynamic pulmonary function testing which was repeated 3-6 months after surgery (n = 53). RESULTS: Thoracotomy alone (n = 13) produced a reduction in forced expiratory volume in one second (FEV1; mean (SE) 2.10 (0.16) versus 1.87 (0.15) l; p<0.05). Wedge resection (n = 13) produced a non-significant reduction in total lung capacity (TLC) only. Lobectomy (n = 14) reduced forced vital capacity (FVC), TLC, and carbon monoxide transfer factor but exercise capacity was unchanged. Only pneumonectomy (n = 13) reduced exercise capacity by 28% (PVO2 23.9 (1.5) versus 17.2 (1.7) ml/min/kg; difference (95% CI) 6.72 (3.15 to 10.28); p<0.01) and three patients changed from a cardiac limitation to exercise before pneumonectomy to pulmonary limitation afterwards. CONCLUSIONS: Neither thoracotomy alone nor limited lung resection has a significant effect on exercise capacity. Only pneumonectomy is associated with impaired exercise performance, and then perhaps not as much as might be expected.

Exercise Test↗

Chromosome location of genes encoding human blood groups.

The chromosomal locations of genes controlling the expression of some 200 antigens constituting the 23 established human blood group systems have been reviewed. Twenty-one of the these genes are located on 12 autosomes, and two are located on the X chromosome. Refined chromosomal positions, to a single cytogenetically distinguishable band, have been established for 13 of the 23 genes. For the remainder, continued investigation will achieve the same result. The genes (RD, MER2, and OK) controlling the expression of one low-incidence and two high-incidence erythrocyte antigens have also been presented. Of these, OK is the most likely candidate for blood group system status, because its chromosomal location distinguishes it from all established system genes except LE and LW, and, the product of the OK gene is different from those of LE and LW (Table 3). This issue will be considered at the next meeting (scheduled for July 1998) of the ISBT Working Party. Alternatively, RD and MER2 are not good candidates for blood group system status because RD and MER2 reside in chromosomal regions containing genes for other blood group systems. In addition, the products of RD and SC have similar biochemical characteristics, and the product of MER2 has not yet been defined (Table 3). The challenge remaining for blood group scientists is characterization of genes that control expression of the approximately 50 other known erythrocyte antigens. Most of these are members of the ISBT's 700 (low-incidence) or 901 (high-incidence) series. Because the current genetic information for each of these antigens (attained by serologic investigation) varies considerably, future studies will have to rely on "tools" from related disciplines to provide the additional information. Use of resources such as molecular biological protocols and GBD should facilitate the effort.

Blood Group Antigens↗

A Gly565-->Ala substitution in human erythroid band 3 accounts for the Wu blood group polymorphism.

BACKGROUND: Reports published in 1976 and 1980 described the low-incidence red cell antigen Wu. Distinction of Wu from all other known low-incidence antigens and from the ABO, Rh, Lutheran, Duffy, Kidd, P, and X-linked blood group systems allowed Wu to be placed in the International Society of Blood Transfusion's 700 series, designated as 700013. Recently, a blood donor apparently homozygous for Wu has been identified. This report documents the serologic and molecular findings of samples from this individual and the members of his family. STUDY DESIGN AND METHODS: Blood samples from 26 members of a kindred of Dutch descent segregating for Wu were collected and analyzed. Red cells were subjected to titration and enzymatic tests, while DNA was analyzed by polyacrylamide gel electrophoresis for single-strand conformational polymorphism (SSCP) and nucleotide differences by DNA sequencing. RESULTS: Serologic investigations conducted on red cells of the propositus and two of his siblings consistently revealed higher titers with various sera containing anti-Wu than did cells from their parents or children. Treatment of intact red cells with alpha-chymotrypsin completely abolished Wu recognition. Because erythroid band 3 is cleaved by alpha-chymotrypsin, the possible relationship between Wu and AE1 (the gene controlling erythroid band 3 expression) was investigated by molecular methods. SSCP analysis of DNA revealed that all Wu+ family members exhibited a mobility shift in exon 14 of AE1. The nature of the SSCP was defined by DNA sequencing as a G-->C mutation that resulted in a Gly565-->Ala substitution in human erythroid band 3. CONCLUSIONS: Three members of the kindred are homozygous for the low-incidence red cell antigen Wu. A G-->C mutation in AE1 gives rise to a Gly565-->Ala substitution in band 3, thereby accounting for the Wu red cell polymorphism. In light of these findings, the International Society of Blood Transfusion Working Party has provisionally assigned Wu to the Diego blood group system (designated 010009 or D19).

Alanine↗

The ELO blood group polymorphism is located in the putative first extracellular loop of human erythrocyte band 3.

BACKGROUND AND OBJECTIVES: The low incidence red cell antigen ELO (700.51) has been excluded from 13 of 23 established blood group systems. Information relative to the Diego system has not been reported. To investigate a possible association between ELO and the gene controlling Diego blood group polymorphisms, we undertook molecular studies of AE1 (anion exchanger 1 gene). MATERIALS AND METHODS: DNA from a family segregating for ELO and from the original ELO proposita was amplified by PCR using intronic primers flanking exons 11-20 of AE1. Subsequently, single-strand conformational polymorphism (SSCP) analysis and DNA sequencing were conducted. RESULTS: We have observed an exon 12 SSCP in all ELO+ individuals tested. This SSCP is the result of a C-->T mutation in exon 12 of AE1 which leads to an Arg432-->Trp amino acid substitution in the putative first extracellular loop of band 3 and thereby accounts for the Diego blood group system polymorphism known as ELO. CONCLUSIONS: In light of these findings, the International Society of Blood Transfusion Working Party on Terminology for Red Cell Surface Antigens has designated ELO as a member of the Diego blood group system (010008 or D18) and rendered the previous numerical designation (700.51) obsolete.

Amino Acid Substitution↗

[Extirpation of the thoracic part of the esophagus using left lateral thoracoabdominal and cervical approach].

From 1988 to 1994 year extirpation of thoracic part of the esophagus with the use of left lateral thoracoabdominal and cervical approach was carried out in 81 patients with cancer of middle (27) and lower (25) thirds of the esophagus and cardia (29). Tumor was removed en bloc with regional lymph nodes, dissected stomach was fixed to the esophageal stump and transferred to the neck, where esophago-gastral anastomosis was created by uninterrupted one-layer suture. 5 patients (6.2%) died after the operation, insufficiency of sutures of the anastomosis was detected in 5 (6.2%) patients, the fistula being spontaneously closed up. Mean duration of the operation made up 309 +/- 48 min, hospitalization 18.4 + 10.9 days. Cumulative actuarial survival rate made up: 1- years--58.9 +/- 5.7%, 3 years--26.9 +/- 6.3%, 5 years-- 20.8 +/- 6.2%. Mean duration of life after the operation was 27.8 +/- 3.4 months.

Actuarial Analysis↗