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Biomedical subjects

A Grant

Publications and source records attributed to A Grant.

At least 163 records · Page 9Linked to original sources
PubMed1993

The interleukin-2 receptor: a target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia.

Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotrophic virus-I (HTLV-I). It is an aggressive leukemia with an overall mortality rate of 50% within 5 months; no conventional chemotherapy regimen appears successful in inducing long-term disease-free survival in ATL patients. However, ATL cells constitutively express high-affinity interleukin-2 receptors (IL-2Rs) identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference in receptor expression, we administered anti-Tac intravenously (IV) to 19 patients with ATL. In general the patients did not suffer untoward reactions, and in 18 of 19 cases did not have a reduction in normal formed elements of the blood. Seven patients developed remissions that were mixed (1 patient), partial (4 patients), or complete (2 patients), with partial and complete remissions lasting from 9 weeks to more than 3 years as assessed by routine hematologic tests, immunofluorescence analysis, and molecular genetic analysis of T-cell receptor gene rearrangements and of HTLV-I proviral integration. Furthermore, remission was associated with a return to normal serum calcium levels and an improvement of liver function tests. Remission was also associated in some cases with an amelioration of the profound immunodeficiency state that characterizes ATL. Thus the use of a monoclonal antibody that blocks the interaction of IL-2 with its receptor expressed on ATL cells provides a rational approach for treatment of this aggressive malignancy.

Adult↗
PubMed1993

Expression of p53 protein in normal, dysplastic, and malignant gastric mucosa: an immunohistochemical study.

Mutations in the p53 nuclear oncogene are the most frequent genetic abnormalities encountered in human malignancies. Using the polyclonal antibody CM-1, we have examined the expression of the p53 oncoprotein immunohistochemically in archival material of normal, dysplastic, and malignant gastric mucosa. Abnormal expression of this protein was not observed in biopsies of normal gastric tissue (n = 30) but was detected in 22 of the 36 gastric cancers analysed (61 per cent). Nuclear staining was diffuse in 15 of the positive cancer cases, the remaining seven showing a more varied heterogeneous staining pattern. Abnormal p53 protein was not detected in mild (n = 14) or moderate (n = 16) gastric dysplasia but was present in 3 out of 15 severe dysplasia cases. The results suggest that expression of the p53 oncoprotein is a common finding in gastric cancer and occurs as a late event in the malignant transformation process.

Antibodies↗
PubMed1993

Midazolam sedation for the reduction of Colles' fractures.

The treatment of Colles' fractures in the elderly comprises a heavy workload for both accident and orthopaedic departments. The initial management has important clinical and financial implications for patient and hospital. The demand is variable and the ability to respond must also be flexible. The choice of anaesthetic technique is therefore most important. In our experience, intravenous sedation with midazolam (a water soluble benzodiazepine) has proven to be safe and effective in providing good conditions for anatomical reduction of Colles' fractures on an outpatient basis.

Aged↗
PubMed1993

The prevalence of paranasal sinus disease in HIV infection and AIDS on cranial MR imaging.

Sinusitis poses a difficult clinical challenge in the management of patients with AIDS because of high rates of relapse and the association with unusual pathogens. To determine the prevalence and severity of sinus disease in this group we prospectively analysed the condition of the paranasal sinuses shown on cranial MR scans of 156 patients referred for the investigation of suspected intracranial pathologies. These included 104 HIV seropositive patients, including 93 with an AIDS-defining diagnosis (CDC IV). Forty-two scans were performed on age-matched controls. The scans were timed to control for seasonal variations in sinus disease and were interpreted by two radiologists who were blinded to the clinical and serological status of the patients. Severe mucosal disease (more than one sinus showing > 75% obliteration) or moderate mucosal disease (only one sinus showing > 75% obliteration) was seen in 15.1% (14/93) patients with AIDS and none of the 42 controls (chi 2 = 6.73, P < 0.01). The mean maximum mucosal thickness in patients with AIDS was significantly greater than the control group (P < 0.001) and also significantly greater than in seropositive patients who had not had an AIDS-defining diagnosis (CDC II/III) (P = 0.006). Paranasal sinus mucosal abnormalities seen on MRI are greater in prevalence and severity in patients with AIDS and about one in seven would be expected to have at least one sinus largely obliterated.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The protein core of the NCA-related pancreatic adenocarcinoma-associated antigen (DD9-Ag) is NCA-50.

Earlier studies with monoclonal antibody (mcAb) DD9E7 have identified a family of nonspecific cross-reacting antigen (NCA)-related antigens that are highly expressed in human pancreatic adenocarcinoma. To analyse the molecular nature of these glycoproteins further, a lambda gt11 expression library has been constructed from the GER pancreatic adenocarcinoma cell line and screened with an NCA sequence-specific oligonucleotide probe. Sequence analysis and restriction enzyme mapping of the clones isolated have shown that they are all homologous with the NCA-50 protein core sequence rather than other related members of the carcinoembryonic antigen/NCA gene family. With use of the same probe, a 2.5-kb mRNA transcript, characteristic of NCA-50, was found in pancreatic adenocarcinoma tumour samples. This study suggests that the 80- to 115-kDa glycoproteins, which we had previously identified in pancreatic adenocarcinomas with NCA-specific mcAb DD9E7, are the result of aberrant glycosylation of the NCA-50 protein core following cell transformation.

Adenocarcinoma↗
PubMed1993

Enzyme-linked immunosorbent assay for p53 in gastrointestinal malignancy: comparison with immunohistochemistry.

Mutations in the p53 nuclear oncogene occur frequently in a wide spectrum of human malignancies and the mutant protein may prove to be a useful diagnostic or prognostic marker. It can be detected in fixed tissues by immunohistochemistry, but the type of fixative and conditions of fixation used can introduce variability. For routine clinical use, a method of analysis which is more easily standardized would, therefore, be of benefit. A two-site enzyme-linked immunosorbent assay (ELISA) was used to measure the level of p53 protein in soluble extracts from 20 gastrointestinal cancers (11 colonic, nine gastric). Immunohistochemistry was also performed on the paraffin-embedded sections of these tumours and the results of the two assays were compared. ELISA detected p53 at various levels in 10 cases, all of which were also positive by immunohistochemistry. Of the other 10, eight were immunohistochemically negative but two were positive. When the immunohistochemically positive specimens were ranked by scoring the degree of staining, there was a highly significant correlation with the quantitative ELISA results. Our study shows that the ELISA is sensitive and highly specific. It offers an alternative and simple method of assessing the p53 status in human tissues.

Adenocarcinoma↗
PubMed1993

Paranasal sinus disease in HIV antibody positive patients.

OBJECTIVE: To investigate the prevalence of radiologically-diagnosed paranasal sinus disease in HIV-1 seropositive patients. SUBJECTS AND SETTING: 476 patients admitted to a dedicated inpatient unit for HIV and AIDS at the Middlesex Hospital, London, between September 1988 and February 1992. DESIGN: Retrospective review of patients' case notes and radiological records. RESULTS: 30 patients (6.3%) had radiological evidence of paranasal sinus disease. At the time of admission, sinusitis was in the differential diagnosis in only 12 of the 30 patients; 13 patients were initially diagnosed as having meningitis. Pseudomonas aeruginosa was the causative organism in four patients, all of whom had advanced HIV disease. All four responded to appropriate antibiotics but had early relapse of infection. CONCLUSIONS: Sinusitis is an important and under-recognised cause of morbidity in patients with HIV disease.

Adult↗
PubMed1993

Blood contamination of the feet during orthopaedic procedures.

Contamination of the feet with blood represents a potential hazard for the surgeon. The incidence of such contamination during major orthopaedic surgery has been shown in this study to be 54%. The use of protective leggings during surgery is recommended.

Blood↗
PubMed1993

Indium-111-labeled polyclonal human immunoglobulin: identifying focal infection in patients positive for human immunodeficiency virus.

Pooled human immunoglobulin labeled with indium-111 (111In-HIgG) was used to identify the presence and extent of infection in patients positive for human immunodeficiency virus (HIV), presenting with either symptoms and/or signs of acute chest infection or with pyrexia without localizing signs or symptoms. Fifty-five studies were performed in 51 patients with suspected chest infection or pyrexia without localizing signs. Of these, 111In-HIgG identified intrapulmonary accumulation in 17 patients with Pneumocystis carinii pneumonia, eight with bacterial pneumonia, five with cytomegalovirus pneumonia, three with pulmonary Mycobacterium avium intracellulare infection and one with a fungal pneumonia. There was no intrapulmonary accumulation of 111In-HIgG in five patients with bronchopulmonary Kaposi's sarcoma and in three patients with intrathoracic lymphoma. Quantification of lung/heart activity was significantly increased (p < 0.05) in patients with active chest infection compared with those with intrapulmonary tumor or no active lung pathology. Indium-111-HIgG scintigraphy also localized at 14 sites of extrapulmonary infection, including six patients with colitis. There were no false-negative studies but false-positive uptake was seen in four studies. These results confirm that 111In-HIgG correctly identifies the presence and extent of infection in patients positive for HIV antibody.

AIDS-Related Opportunistic Infections↗
PubMed1993

Questions of life and death.

The continuous evolution of health care technology has brought with it a growing need to evaluate the quality of the lives it saves or prolongs. Do Not Resuscitate (DNR) orders, euthanasia and living wills all raise the issue of who decides about the quality of a person's life. Although nurses and other health care professionals have developed codes of ethics to deal with these difficult evaluations, ethics are not law. Ethics are derived from culture, religion and societal and individual concepts of morality. Law is the set of rules a society chooses to enact and enforce. Real difficulty arises when health care providers must face a situation where personal and professional codes of ethics clash with the law.

Decision Making↗
PubMed1993

Epidemiological principles for the evaluation of monitoring programs--the Dublin experience.

There is no gold-standard measurement for 'fetal asphyxia'; methods of fetal surveillance must therefore be evaluated in the context of a management program that includes clinical intervention when a diagnosis of 'fetal compromise' is made. The use of non-randomized comparison groups is prone to major bias which can only be avoided satisfactorily by random assignment of alternative monitoring policies. To avoid being misled by random errors, randomized controlled trials must be surprisingly large. The hypothesis, generated from the results of four small trials (total of 2,000 women), that more intensive intrapartum monitoring reduces the risk of neonatal seizures, was tested and sustained in the larger Dublin trial (13,000 women). Early-onset neonatal seizures now provide the best validated epidemiological index of obstetrically-preventable intrapartum asphyxia at or after term. Paediatric follow-up at age 4 failed to identify any beneficial effect of intensive monitoring on cerebral palsy, despite the protective effect on neonatal seizures. The results of the Dublin trial are consistent with those of comparable trials, and this enhances the generalizability of the study's results.

Asphyxia Neonatorum↗
PubMed1992

[Surgical cerclage in the treatment of cervical incompetence during pregnancy (determining the legitimacy of the procedure)].

The authors studied the effectiveness of the cervical cerclage operation in the therapy of cervical insufficiency during the pregnancy. Two Hundred sixteen pregnant women took part in this trial in whose pregnancy the necessity of cerclage operation was not unequivocal. It means, that the therapeutical cerclage operation was not necessary, but the necessity of prophylactic cerclage operation was doubtful as well. From the randomized 216 cases they performed cerclage operation in 108 pregnancies and in 108 cases they did not perform it. In the respect of pregnancy care they did not make any difference between the two groups. The authors from their trial draw the conclusion, that in doubtful cases where the necessity of cervical cerclage operation is not unequivocal--e.g. at serious gestational case history--it is advisable to perform the operation. The danger of premature birth can be diminished in this way.

Female↗
PubMed1992

Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration.

The high birthweights and long duration of pregnancy in the Faroe Islands led us to suggest that a high intake of marine-fat-derived n-3 fatty acids might prolong pregnancy by shifting the balance of production of prostaglandins involved in parturition. We have compared the effects on pregnancy duration, birthweight, and birth length of a fish-oil supplement, a control olive-oil supplement, and no supplementation. 533 healthy Danish women in week 30 of pregnancy were randomly assigned in a ratio of 2/1/1 to fish oil (four 1 g Pikasol capsules [containing 2.7 g n-3 fatty acids] per day), olive oil (four 1 g capsules per day), or no supplement. The three groups differed in mean length of gestation (p = 0.006), which was highest in the fish-oil group and lowest in the olive-oil group; the result was similar when the analysis was restricted to women with an estimate of gestation length based on early ultrasound findings (443 women). Pregnancies in the fish-oil group were on average 4.0 (95% confidence interval 1.5-6.4) days longer than those in the olive-oil group; the difference in birthweight was 107 (1-214) g. The effect of supplementation on length of gestation was influenced by intake of fish and of fish oil: the difference between fish-oil and other groups was increased by a low fish intake at baseline. Fish-oil supplementation in the third trimester seems to prolong pregnancy without detrimental effects on the growth of the fetus or on the course of labour.

Adult↗