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Biomedical subjects

P O'Gorman

Publications and source records attributed to P O'Gorman.

At least 19 recordsLinked to original sources

Dietary vitamin B12 deficiency in an adolescent white boy.

Dietary deficiency of cobalamin resulting in tissue deficiency in white individuals is unusual. However, several patients with dietary deficiency who were neither vegan nor Hindu have been described. This report describes the case of a 14 year old boy who was a white non-Hindu with a very low intake of cobalamin, which was not apparent until a detailed dietary assessment was performed. The patient responded rapidly to a combination of oral and parenteral B12. This case illustrates the fact that severe dietary vitamin B12 deficiency can occur in non-Hindu white individuals. Inadequate dietary content of B12 may not be apparent until a detailed dietary assessment is performed. This patient is likely to have had subclinical vitamin B12 deficiency for several years. Increased vitamin B12 requirements associated with the adolescent growth spurt may have provoked overt tissue deficiency.

Adolescent↗

Continuous infusion of porcine factor VIII in patients with haemophilia A and high-responding inhibitors: stability and clinical experience.

A multicentre retrospective survey was conducted to assess the efficacy and side-effect profile of porcine factor VIII (pFVIII:C) given by continuous infusion (CI) to patients with congenital haemophilia A and inhibitors. Twenty-nine episodes in 18 patients were treated by CI of pFVIII:C. Efficacy was graded as good in 79% of infusions and fair in 17%. There was a failed response in only one episode. Fourteen percent of patients experienced transfusion reactions with bolus doses, but no reactions were observed in patients given CI. There were no severe reactions. All the reactions resolved following interruption of the infusion and administration of steroids. Premedication did not prevent reactions. In this series the median decrease in platelet count after bolus injection of pFVIII:C was -67 X 10(9) L(-1) compared with a median decrease of -2 x 109 L(-1) during the course of CI, thus, continuous infusion of pFVIII:C appears to have less effect on platelet count than bolus injection. An anamnestic response was associated with 77% of infusions. This high rate of anamnesis reflects patient selection, in that they were all known to have high-level high-responding FVIII inhibitors with cross-reactivity to pFVIII. After reconstitution, the pFVIII:C showed little loss in factor VIII activity in solution over a 24-h period. We conclude that pFVIII:C may be effectively administered by CI to patients with haemophilia A and high-responding FVIII inhibitors. CI is the probably the mode of administration of choice for intensive replacement therapy with pFVIII.

Adolescent↗

Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss.

The association between hypoalbuminemia and poor prognosis in patients with cancer is well recognized. However, the factors that contribute to the fall in albumin concentrations are not well understood. In the present study, we examined the relationship between circulating albumin concentrations, weight loss, the body cell mass (measured using total body potassium), and the presence of an inflammatory response (measured using C-reactive protein) in male patients (n = 40) with advanced lung or gastrointestinal cancer. Albumin concentrations were significantly correlated with the percent ideal body weight (r = 0.390, p < 0.05), extent of reported weight loss (r = -0.492, p < 0.01), percent predicted total body potassium (adjusted for age, height, and weight, r = 0.686, p < 0.001), and log10 C-reactive protein concentrations (r = -0.545, p < 0.001). On multiple regression analysis, the percent predicted total body potassium and log10 C-reactive protein concentrations accounted for 63% of the variation in albumin concentrations (r2 = 0.626, p < 0.001). The interrelationship between albumin, body cell mass, and the inflammatory response is consistent with the concept that the presence of an ongoing inflammatory response contributes to the progressive loss of these vital protein components of the body and the subsequent death of patients with advanced cancer.

Aged↗

In vitro cold activation of complement shown by an overestimation of total complement 4: a study in patients with hepatitis C virus infection.

Total complement 4 (C4) levels, when analysed on the Beckman Array nephelometer, were found to increase number of serum specimens [predominantly from patients with hepatitis C virus (HCV) infection] after overnight storage at 4 degrees C. In order to investigate whether the phenomenon of in vitro cold-dependent activation of complement (CDAC) was the explanation for this increase, paired specimens were collected from 63 patients with HCV infection in tubes with no anticoagulant (serum) and in tubes containing EDTA (which inhibits complement activation). C4 levels increased after overnight storage at 4 degrees C in 33 serum specimens (52%). In contrast, no increase in C4 levels was observed in any of the 63 EDTA specimens. Immunofixation of intact and activated C4 products confirmed that complement activation had taken place in the serum specimens in which C4 levels had increased after storage. There was a higher frequency of hepatitis C viraemia (P<0.0001), HCV antibody positivity (P<0.05) and the presence of rheumatoid factor (P<0.05) in the group of patients in whose serum samples CDAC had occurred (n = 33) than in the other group (n = 30). As a result of our findings on C4 analysis in stored serum specimens, we would recommend potassium EDTA plasma as the specimen of choice for complement analysis on the Beckman Array.

Blood Chemical Analysis↗

Optimization of routine plasma homocysteine monitoring.

An elevated plasma homocysteine (Hcy) level is now considered to be an important risk factor in arterial and venous thromboembolic events. As a result of this relatively recent finding, there has been a dramatic increase in the number of requests for Hcy measurement. In our laboratory, this demand has been met by employing an automated immunoassay and improving the pre-analytical handling of blood samples. An automated fluorescent polarization immunoassay (FPIA) gave similar results to a reference high-pressure chromatographic (HPLC) method (r2 = 0.98, enzyme immunoassay = 0.998 HPLC - 0.3) and excellent between-run reproducibility (coefficient of variation <3%). The new assay also required less specialized technical input, and improved the sample throughput two-fold. Pre-analytical stability of plasma Hcy concentrations in blood samples is crucial to the accuracy of Hcy monitoring. This stability was improved 10-fold by adopting the anticoagulant acidic citrate instead of ethylenediamine tetraacetic acid for Hcy screening by FPIA. Acidic citrate dramatically inhibits time-related plasma contamination by red-cell Hcy, resulting in improved accuracy and a reduced number of 'spoiled' specimen discards.

Drug Monitoring↗

Prognostic factors in advanced gastrointestinal cancer patients with weight loss.

There are few reports on factors that determine survival in advanced gastrointestinal cancer with weight loss. In these patients (n = 91, median weight loss 16.6%), we prospectively examined the importance of metastatic spread, anthropometry, blood parameters, Karnofsky performance status, appetite, and the acute-phase response as predictors of survival. Survival was calculated from date of assessment to the most recent clinic attendance (> or = 30 mo) or until death. On multivariate analysis, metastatic spread (p < 0.05), Karnofsky performance status (p < 0.01), and C-reactive protein concentration (p < 0.001) had independent prognostic value. In locally advanced disease (n = 64), Karnofsky performance status and C-reactive protein concentration remained significant. There was a significantly lower survival in patients with an acute-phase response (median 136 days) than in patients with no response (median 466 days; p < 0.01). Performance status and the acute-phase response are associated, independent of weight loss, with survival duration in advanced gastrointestinal cancer patients.

Acute-Phase Reaction↗

Evaluation of novel assays in clinical chemistry: quantification of plasma total homocysteine.

BACKGROUND: There is a need for systematic evaluation of methods before their release to the market. We addressed this problem in novel homocysteine assays as part of an European Demonstration Project involving six centers in four countries. METHODS: Two immunological methods for measurement of plasma total homocysteine (P-tHcy), the fluorescence polarization immunoassay (FPIA) and the enzyme immunoassay (EIA), were compared with two comparison methods, HPLC and gas chromatography-mass spectrometry (GC-MS). All laboratories performed the following procedures: (a) familiarization; (b) determination of linearity and precision by analyzing five plasma samples with interrelated concentrations for 20 days; (c) correlation using patients' samples; and (d) assessment of long-term performance. RESULTS: Both immunological methods were linear for P-tHcy between 5 and 45 micromol/L. The intralaboratory imprecision (CV) was <5% for FPIA and <9% for EIA used with a sample processor. The bias was -2% to 3% for FPIA and 2-4% for EIA used with a sample processor. CONCLUSIONS: The immunological methods provide results with little bias compared with HPLC and GC-MS. The imprecision of the assays must be considered in the context of their intended use(s).

Fluorescence Polarization Immunoassay↗

A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss.

The use of megestrol acetate in the treatment of weight loss in gastrointestinal cancer patients has been disappointing. The aim of the present study was to compare the combination of megestrol acetate and placebo with megestrol acetate and ibuprofen in the treatment of weight loss in such patients. At baseline, 4-6 weeks and 12 weeks, patients underwent measurements of anthropometry, concentrations of albumin and C-reactive protein and assessment of appetite, performance status and quality of life using EuroQol-EQ-5D and EORTC QLQ-C30. Thirty-eight and 35 patients (median weight loss 18%) were randomized to megestrol acetate/placebo or megestrol acetate/ibuprofen, respectively, for 12 weeks. Forty-six (63%) of patients failed to complete the 12-week assessment. Of those evaluable at 12 weeks, there was a decrease in weight (median 2.8 kg) in the megestrol acetate/placebo group compared with an increase (median 2.3 kg) in the megestrol acetate/ibuprofen group (P<0.001). There was also an improvement in the EuroQol-EQ-5D quality of life scores of the latter group (P<0.05). The combination of megestrol acetate/ibuprofen appeared to reverse weight loss and appeared to improve quality of life in patients with advanced gastrointestinal cancer. Further trials of this novel regimen in weight-losing patients with hormone-insensitive cancers are warranted.

Aged↗

Longitudinal study of weight, appetite, performance status, and inflammation in advanced gastrointestinal cancer.

There is increasing evidence that, in most patients with advanced cancer, weight loss is associated with an inflammatory response. To examine the temporal relationship between weight loss, appetite, performance status, and the inflammatory response, 50 patients with advanced gastrointestinal cancer with weight loss were observed for six weeks. Patients were grouped according to whether they had lost weight (> 3%, n = 16), were weight stable (< 3% change, n = 25), or gained weight (> 3%, n = 9). At baseline, the group that subsequently lost weight had lower albumin and higher C-reactive protein concentrations (p < 0.05). On follow-up, there was an increase in C-reactive protein concentration and reductions in triceps skinfold thickness and Karnofsky performance status in the weight-losing group (p < 0.05). In contrast, Karnofsky performance status was improved in the group that gained weight (p < 0.05). Over the six to eight weeks, there was a difference in the changes of triceps skinfold thickness (p < 0.05) and Karnofsky performance status (p < 0.01) between the two groups. These results suggest that loss or gain of > 2.5 kg over a six- to eight-week period is required to produce a significant alteration in performance status in weight-losing patients with gastrointestinal cancer. Moreover, the results suggest that the presence of an inflammatory response is associated with further weight loss and the deterioration of performance status.

Adult↗

Impact of weight loss, appetite, and the inflammatory response on quality of life in gastrointestinal cancer patients.

The relationship between weight loss, appetite, the inflammatory response, and quality of life in patients with advanced gastrointestinal cancer was examined. Height, weight, and skinfold anthropometry were measured in 119 patients. Blood was taken for analysis of C-reactive protein and albumin. Appetite, performance status, and quality of life were assessed using EuroQol EQ-5D and EORTC QLQ-C30 questionnaires. Weight loss was > 5% (median 17.1%) of their preillness weight in 97 patients; the remaining 22 patients were weight stable. Anthropometric measurements and circulating albumin concentrations were significantly lower (p < 0.01) and circulating concentrations of C-reactive protein were significantly higher in the weight-losing than in the weight-stable group (p < 0.001). Appetite scores, performance status, and EuroQol EQ-5D and EORTC QLQ-C30 scores were also lower in the weight-losing group (p < 0.01). When the weight-losing cancer patients were divided on the basis of whether they had a marked inflammatory response, albumin concentrations, appetite, and Karnofsky performance status were significantly lower (p < 0.05) in the group with a marked inflammatory response. The results of the present study are consistent with weight loss, reduction of appetite, and an elevated inflammatory response being important related factors in lowering the quality of life of gastrointestinal cancer patients.

Aged↗

Doppler index perfusion in the detection of hepatic metastases secondary to gastric carcinoma.

BACKGROUND: The early detection of liver metastases in patients with gastric carcinoma is important for determining the appropriate therapy; however conventional imaging techniques are limited for detecting "occult" liver metastases. Previous studies have shown that the measurement of the Doppler perfusion index (DPI)-ratio of hepatic arterial to total liver blood flow-can detect the presence of even small hepatic tumors. In this study, we compared the measurement of DPI with computed tomography (CT) for detecting gastric liver metastases. METHODS: At presentation, 43 patients with gastric carcinoma underwent CT scanning of the liver and after 12 hours of fasting, DPI measurement was carried out using Doppler sonography. RESULTS: Both techniques detected overt liver metastases in 9 of the 43 patients. Of the 34 remaining patients with an apparently disease-free liver on the basis of CT, laparotomy, or laparoscopy, 14 subsequently develop liver metastases over a follow-up period of 4 years, 13 of which had been predicted by DPI at the time of presentation. CONCLUSION: The data suggest that the measurement of the DPI is more sensitive than a CT scan for detecting liver metastases secondary to gastric carcinoma.

Aged↗

A pilot study of megestrol acetate and ibuprofen in the treatment of cachexia in gastrointestinal cancer patients.

Advanced gastrointestinal cancer patients with weight loss and an acute-phase response (n = 15) were given megestrol acetate (480 mg day(-1)) and ibuprofen (1200 mg day(-1)) for 6 weeks. Overall, there was an increase in body weight (P = 0.01) and a reduction in C-reactive protein concentrations (P = 0.02), with no change in total body water (P = 0.24) over this period. This regimen may be an effective non-toxic treatment for cancer cachexia and is worthy of further study.

Adult↗

Intraoperative ultrasound in colorectal cancer patients undergoing apparently curative surgery: correlation with two year follow-up.

Conventional ultrasound (US) and computerized tomography (CT) are well recognized to be limited in the detection of small liver metastases. In this study, we assessed the use of intraoperative ultrasound (IOUS) in the detection of 'occult' liver metastases in colorectal cancer patients undergoing apparently curative surgery of the primary colonic carcinoma. Ninety three colorectal cancer patients undergoing apparently curative surgery on the basis of preoperative US, CT and laparotomy were studied. All patients underwent IOUS examination of the liver. After two year follow-up, 27 of these 93 patients developed overt liver metastases and of these 27, only five had been detected by IOUS examinations at the time of laparotomy. The results suggest that IOUS is relatively insensitive in the detection of occult colorectal liver metastases. Its routine use as a screening tool during primary surgery is therefore not recommended.

Colorectal Neoplasms↗

MALTectomy (appendectomy/tonsillectomy) does not influence the occurrence or mode of presentation of adult celiac disease.

OBJECTIVE: Recent reports suggest that appendectomy may protect against the development of ulcerative colitis. Depletion of mucosal helper T-cells is the suggested mechanism. Because mucosal T-cell activity has an even more critical role in the pathogenesis of celiac disease, our objective was to determine whether the development or mode of presentation of this disorder is influenced by appendectomy and/or tonsillectomy. METHODS: One hundred fifty consecutive adult celiac patients were compared with 138 consecutive patients examined at orthopedic clinics. One hundred twenty consecutive patients with ulcerative colitis from the same ethnogeographic population were included as positive disease control. RESULTS: Contrary to the previous findings in ulcerative colitis, which were again confirmed in this study, appendectomy and/or tonsillectomy did not influence the occurrence of celiac disease. In addition, presenting features, predefined in the study protocol, did not differ significantly in the appendectomy and nonappendectomy celiac patients. CONCLUSION: Resection of mucosa-associated lymphoid tissue (MALT) does not influence the occurrence or the mode of presentation of adult celiac disease. Therefore, in this classical example of a T-cell-mediated disorder, the hypothesis that surgical depletion of mucosal T-cells has a protective effect or influences the clinical manifestations cannot be supported.

Adult↗

Improved sensitivity of colour Doppler flow imaging of colorectal hepatic metastases using galactose microparticles: a preliminary report.

The clinical application of ultrasonographic contrast agents in colour Doppler flow imaging of hepatic tumours is receiving increasing attention. Levovist is a suspension of galactose microparticles that provides reproducible concentrations of stabilized air bubbles with transpulmonary stability. Its effect on colour Doppler imaging was assessed in 26 patients with colorectal cancer and histologically proven hepatic metastases. Colour Doppler flow imaging was performed before and after intravenous injection of 10 ml Levovist 300 mg/ml. At 5-10 s after injection there was significant enhancement of the hepatic lesions with colour Doppler signals in 23 patients, lasting for a mean(s.d.) of 180(45) s. A consistent pattern of colour Doppler signal was observed, with increased enhancement predominantly around the tumour periphery and little or no central enhancement. These data suggest that Levovist may increase the sensitivity and specificity of colour Doppler flow imaging of colorectal hepatic metastases.

Adult↗

A phase II study of regional 5-fluorouracil infusion with intravenous folinic acid for colorectal liver metastases.

Regional chemotherapy, delivered via the hepatic artery, may significantly increase tumour response rates in patients with colorectal liver metastases. However, survival is limited by extrahepatic disease progression. We have developed a novel therapeutic approach for patients with metastases confined to the liver. In order to achieve high local response rates and also inhibit extrahepatic progression, 5-fluorouracil (5-FU) was infused intra-arterially at a dose previously calculated to achieve both high-dose regional therapy and adequate systemic levels. To enhance efficacy further, 5-FU was combined with high-dose systemic folinic acid (FA). Thirty-one patients were evaluated in a phase II study. 5-FU (1.5 g m2) was infused via a surgically implanted hepatic artery catheter over a 24 h period; FA (total 400 mg m-2) was infused intravenously during the initial and final 2 h. Treatments were given weekly for cycles of 6 weeks' duration. To date, median duration of treatment is 6 months and the median follow-up period is 17 months. The overall response rate was 48% with two complete and 13 partial responses. Predicted median time to progression is 8 months. The site of first progression was hepatic in 10 (42%) and extrahepatic in 14 (58%) patients. Seven patients developed local complications; one required emergency surgery. Side-effects were limited to grade 3 toxicity (four patients) or less. Predicted median survival is 19 months. This approach, which is associated with a high response rate and low systemic toxicity, warrants further evaluation. A phase III study is planned.

Adult↗

Pharmacokinetic study of 5-fluorouracil in a novel dialysate solution: a long-term intraperitoneal treatment approach for advanced colorectal carcinoma.

Five patients with advanced colorectal and gastric carcinoma with peritoneal deposits were treated by continuous weekdays intraperitoneal (i.p.) instillation of 5-fluorouracil (5-FU) 200 mg m-2 day-1 in a novel dialysate solution that ensures maximal exposure of peritoneal areas liable to bear tumours for 24 h. A solution of icodextrin, a glucose polymer, in a 21 twin-bag delivery system allowed a single daily exchange and demonstrated the feasibility of long-term continuous ambulatory treatment with up to 17.4 g of 5-FU, delivered intraperitoneally, in this initial study. During the entire study, there were 235 fluid exchanges or 470 connections and disconnections and no bacterial peritonitis or exit site infection were observed. There was no treatment-associated toxicity worse than WHO grade 2. Drug concentrations in both peritoneal and plasma compartments followed a first-order model with similar half-life value of 1.3 h. 5-FU pharmacokinetic parameters (half-life values, total body clearance, peritoneal clearance and pharmacological advantage of the i.p. route) with this novel icodextrin carrier solution were similar to those obtained in other referenced pharmacokinetic studies with other carrier solutions (dextrose dialysate and lactated Ringer's solutions). This confirms that icodextrin solution is physiologically neutral, drug compatible and allows adequate dwell times with constant fluid balance for long-term continuous intraperitoneal chemotherapy. The pharmacokinetic parameters from this study will be used to design a loading dose infusion schedule in an attempt to maintain steady-state i.p. 5-FU levels in a new multicentre phase I trial.

Colorectal Neoplasms↗

Codependency explored: a social movement in search of definition and treatment.

This article will explore why so many women, and most recently men, have been diagnosing themselves as codependent. It will be suggested that defining codependency as learned helplessness can provide the needed conceptual base to empower those codependents who are also seeking treatment. Empowerment is needed by those women and men who grew up in the types of dysfunctional families that offer them little protection from dysfunctional family rules. The alcoholic family will be explored as one of the family systems which generates large numbers of those feeling that they are codependent. Treatment guidelines will be offered for working with codependents who also decide on a course of psychotherapy.

Adult↗