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Biomedical subjects

K Ward

Publications and source records attributed to K Ward.

At least 145 records · Page 8Linked to original sources

Comparison of immunofluorescence and enzyme immunoassay for detection of measles-specific immunoglobulin M antibody.

During a measles outbreak, 283 serum specimens from 221 suspected cases of measles were tested by immunofluorescence and enzyme immunoassay for the presence of measles-specific immunoglobulin M (IgM) antibodies by using commercially available reagents. There was 97% agreement between the two assays; thus, the choice of the method for diagnostic testing is a matter of convenience and experience. In all 62 cases of measles from which a single blood sample was available, measles IgM-specific antibodies were detectable by both methods. Fifty percent of the 62 cases were positive within 3 days after onset of the rash. This increased to 91% 10 days after onset of the rash.

Adolescent↗

Analysis of patients lost to follow up at a sarcoid clinic.

An analysis was made of an outpatient population attending a specialized sarcoidosis clinic in order to identify and quantify the number of patients who had become lost to follow up. In addition we wished to elucidate the reasons why they had not returned and to determine the consequences, if any, of not having continuing medical surveillance. Ninety-four patients were identified as being lost to follow up from our specialized sarcoidosis clinic and were invited to return for review. Forty-six patients (49%) responded and were evaluated. The main reason for clinic non-attendance given by 91% (42/46) of the clinic reattenders was that they were asymptomatic. Comparing this group with a cohort of 50 patients who are regular clinic attenders, we found that the lost to follow up patients had a strikingly more benign disease profile. In spite of this, analysis of this respondent group revealed some evidence of continuing disease activity or progression, with 37% (17/46) of the group fulfilling at least one of our defined criteria for disease progression. While none of these patients warranted the immediate addition of corticosteroid medication at their first recall visit, their continuing disease activity warrants close supervision at a specialized sarcoidosis clinic. We conclude that educational strategies require to be developed in order to minimize clinic non-attendance by patients with sarcoid. Furthermore more positive action needs to be taken by clinicians in attracting those patients, who become lost to follow up, to return for clinic review.

Adult↗

Cystic fibrosis in adolescents and adults.

A cystic fibrosis (CF) clinic for adults was established in 1977. We have reviewed the data on 164 patients who attended between 1977 and 1989. Twenty four patients had died, 11 being over 20 years after time of death. Of the 140 patients still alive, 61% were male and 53% were aged over 20 years. Only 55% were diagnosed by 1 year and 88% by 10 years. Almost all patients had respiratory symptoms and sputum culture yielded Pseudomonas species in 69%. Other respiratory problems included major haemoptysis and pneumothorax, each in 10%. We found a wide range of respiratory impairment among older patients. Among 3 patients aged over 23 years the mean (+/- S.D.) percent predicted FEV1 and FVC were 53.3% (+/- 18%) and 71.4% (+/- 20%) respectively. Mean weight in this group was 92.5% (+/- 14) of predicted. Malabsorption occurred in most patients and meconium ileus equivalent occurred in most patients and meconium ileus equivalent occurred in 34%. Other complications were clinical hepatomegaly (16%), diabetes mellitus (9%) and arthropathy (20%). Most patients were taking continuous antibiotics by mouth (89%) and by nebuliser (48%), beta-2 agonists by inhaler (57%) and oral steroids (29%). Almost all were taking multivitamins, pancreatic replacement therapy and multiple nutritional supplements. The number of CF "bed days" grew 12 fold since 1979 and the mean stay in hospital was double the hospital mean. The economic impact was such that over 1/4 of the annual hospital antibiotic budget was expended on CF patients.

Adolescent↗

Qualitative and quantitative analysis of peritoneal fluids from women with gynecologic diseases. Comparison of cytology and flow cytometry for the detection of malignancy in lavage and ascitic fluids.

A prospective study was undertaken to compare flow cytometric (FCM) analysis to conventional cytologic evaluation for the detection of malignant cells in peritoneal fluids (peritoneal lavages and ascitic fluids) from women with gynecologic diseases. The 94 peritoneal fluids analyzed came from 63 cancer patients (with epithelial ovarian carcinomas) and 31 control patients (with benign gynecologic diseases). The FCM DNA histograms were generated using propidium iodide as a DNA fluorochrome. Samples for cytologic analysis were stained with the standard May-Grünwald-Giemsa or Papanicolaou stains. Of the 94 samples, 90 were evaluable cytologically while 70 were suitable for FCM analysis. The sensitivities were 55% for FCM DNA analysis and 80% for cytologic analysis. FCM DNA analysis had a 30% false-positive rate; cytologic analysis produced no false-positive results. These results indicate that there is no advantage in employing FCM analysis instead of conventional cytologic evaluation for the detection of malignant cells in peritoneal fluids from gynecologic cases.

Adolescent↗

Isolated CNS involvement in Ewing's sarcoma.

Ewing's sarcoma, an uncommon malignant neoplasm of bone, represents about 10% of all the malignant primary bone tumors. The assumption that subclinical metastases are already present in patients with apparently localized tumor indicates the need for systemic therapy as an integral part of primary treatment. The usual sites of metastases are the lungs and skeletal system. Central nervous system (CNS) involvement is rare and is usually seen only in disseminated and fairly advanced disease. We report two patients in whom, after aggressive adjuvant chemotherapy, disease developed in the CNS without local recurrence. In one patient, meningeal involvement with malignant cells was identifiable in the cerebrospinal fluid; in the second patient, who presented with a space-occupying lesion, a diagnosis of arachnoid involvement was made histologically.

Adolescent↗

Prenatal diagnosis and linkage disequilibrium with cystic fibrosis for markers surrounding D7S8.

Three polymorphic DNA markers surrounding the D7S8 locus were tested for their usefulness in the diagnosis of cystic fibrosis (CF) by linkage analysis. The markers correspond to the loci D7S424 and D7S426. These polymorphisms were studied by centers in the U.S., the United Kingdom, the Netherlands, and Italy, using samples from populations throughout Europe and North America. The additional information provided by these probes increased the heterogeneity of the region from 50% to 58% and was essential for a completely informative diagnosis in one family. A very high degree of linkage disequilibrium was found between these markers, which span a distance of approximately 250 kb. In addition, linkage disequilibrium with CF was noted. Significant heterogeneity of linkage disequilibrium was found among the populations, both for the marker-marker pairs and between the markers and CF.

Cystic Fibrosis↗

Tumour cell activity markers in epithelial ovarian cancer: are biochemical and cytometric indices complementary?

Flow cytometry has enabled the objective assessment of cellular morphology and activity, which can also be biochemically evaluated by measuring products of cellular metabolism, such as cyclic 3'5' guanosine monophosphate (cGMP). Using paraffin-embedded formalin-fixed material obtained from the primary operation, an analysis of the correlation between nuclear ploidy and the proliferative index (PI) as quantified by flow cytometry with pre-treatment urinary cGMP was performed in 40 epithelial ovarian cancer (EOC) patients. The majority of the study group had advanced disease (28 FIGO III/IV) and residual disease (31). All but three (stage I) patients received single agent high dose cisplatinum as first-line therapy (100 mg m-2 x 5); in patients with evaluable disease there was a response rate of 64%. Thirty-one patients have died; the median survival of the study population being 27 months. There was a significant association between cGMP and PI. Significantly more aneuploid tumours had elevated PI values (P = 0.02). No variable predicted response. An initial univariate log rank analysis identified stage, the amount of residual disease, cGMP and PI as prognostic factors. Because of the interrelation between these and other factors and because PI did not conform to the proportional hazards model, a multivariate stepwise discriminant analysis was performed using survival at 36 months (the minimum follow-up for surviving patients) as the end-point. On the basis of this analysis, stage and residual disease were the most important prognostic factors, but cyclic GMP continued to have prognostic value even when these other factors were entered into the predictive model. However, the additional information gained has little clinical relevance.

Biomarkers, Tumor↗

Expression and secretion of a functional scorpion insecticidal toxin in cultured mouse cells.

We have expressed a synthetic gene encoding the insecticidal neurotoxin of scorpion Androctonus australis (AaIT) in NIH/3T3 mouse fibroblast cells under the transcriptional control of a murine retroviral long terminal repeat. The secretion of the toxin into the culture medium was directed by the signal peptide of human interleukin-2. The recombinant AaIT produced was selectively toxic to yellow-fever mosquito larvae and harmless to mice.

Aedes↗

Invasive cervical cancer after laser vaporization for cervical intraepithelial neoplasia: a 10-year experience.

The treatment of cervical intraepithelial neoplasia by laser vaporization has been in progress at the Birmingham and Midland Hospital for Women since September 1977. In this interval, 3182 patients have been treated. Seven women have developed invasive cancer at intervals 4-34 months postlaser. The lesions diagnosed were stage Ia (3), Ib (1), IIb (1), IIIa (1), and IV (1). These case histories are presented. On retrospective assessment, there were contraindications to local destructive treatment in six of seven cases. This series emphasizes the need for thorough evaluation of patients before embarking on local destructive treatments and emphasizes the need for careful follow-up of treated patients.

Adult↗

Bronchoalveolar lavage in patients with mild and severe rheumatoid lung disease.

The reported prevalence of interstitial lung disease in patients with rheumatoid arthritis has varied from 10% to 50%, yet less than 5% of patients with arthritis develop severe fibrosing interstitial lung disease. This suggests that subclinical disease may not always presage progressive disease. Bronchoalveolar lavage fluid from patients with rheumatoid arthritis and either clinically evident interstitial lung disease or subclinical disease was examined for the presence of factors with a putative role in the development of interstitial fibrosis. Patients with subclinical disease were identified by prospective radiographic and lung function screening of 93 patients with rheumatoid arthritis. Fourteen patients were identified in this manner and an association between subclinical disease and smoking history was noted. Eleven patients with established interstitial lung disease had increased neutrophils (p less than 0.05), collagenase, and type III procollagen N terminal peptide levels (p less than 0.01) in the bronchoalveolar lavage fluid. Preliminary characterisation of the bronchoalveolar lavage collagenase suggested that it originated from neutrophils. Ten patients with subclinical interstitial lung disease underwent bronchoalveolar lavage. Of these, one had increased neutrophils and two had increased collagenase concentrations--abnormalities associated with advanced interstitial lung disease and a poor prognosis. These results suggest that in arthritis patients with evidence of subclinical pulmonary interstitial disease bronchoalveolar lavage might be useful in identifying those who may require careful monitoring in the hope that early treatment will prevent severe fibrosis.

Adult↗

Pulmonary disease progress in sarcoid patients with and without bronchoalveolar lavage collagenase.

To assess the usefulness of bronchoalveolar lavage (BAL) collagenase measurement in gauging disease severity and outcome in sarcoidosis, we analyzed BAL fluids from 84 patients with sarcoidosis for collagenase and monitored disease progress in these patients for a minimum of 12 months. Twenty patients (24%) were found to have BAL collagenase activity on initial evaluation (collagenase-positive group). Compared with patients without BAL collagenase (collagenase-negative group), the collagenase-positive group had (1) a higher proportion of BAL suppressor T cells (p less than 0.03); (2) a lower helper-suppressor T-cell ratio (p less than 0.002); (3) lower mean percent predicted FEV1, FVC, and DLCO levels (p less than 0.05); and (4) a higher proportion of patients with advanced (Stage 4) disease on chest roentgenogram (p less than 0.001). Significant differences were also observed between the collagenase-positive and collagenase-negative groups during follow-up. A higher proportion (55%, n = 11) of collagenase-positive patients required corticosteroid therapy than did collagenase-negative patients (26%; n = 17; p less than 0.025). Of those who remained untreated, pulmonary function tended to decrease in the collagenase-positive group, whereas mean pulmonary function levels actually improved in the collagenase negative group (p less than 0.05). Of those who required therapy, mean percent predicted FVC and DLCO levels improved significantly after treatment in the collagenase-negative group (p less than 0.01 and p less than 0.05, respectively), whereas an improvement in percent predicted FVC levels only (p less than 0.01) was observed in the collagenase-positive group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

Diagnosis of neurofibromatosis I by using tightly linked, flanking DNA markers.

We tested 132 individuals from 21 families segregating an allele for neurofibromatosis type 1 (NF-1), by using nine RFLPs tightly linked to the NF-1 locus. Family members had requested DNA testing either to determine whether "at risk" children were carrying the NF-1 allele or to determine whether their respective families would be informative for prenatal testing. Predictions about whether a child carries the NF-1 mutation were possible for all 32 at-risk offspring (greater than 98% accuracy based on the recombination estimates currently available for these DNA markers). At least one informative probe was available for all 23 matings in these 21 families; flanking markers were informative for 10 matings. Pairwise analysis showed that several of the polymorphisms were in tight linkage disequilibrium; few recombination events were observed with these markers in the families under study. We conclude that the DNA probes used in this study perform well for diagnostic testing of NF-1 in familial cases. A subset of five probe-enzyme systems (pHHH202/RsaI, p11-3C4.2/MspI, pTH17.19/Bg/II, p11-2C11.7/BamHI, and p11-2F9.8/TaqI) provide reliable linkage information for both clinical testing and prenatal diagnosis.

Alleles↗

Indicators of effective cytological sampling of the uterine cervix.

A case-control comparison of adequate and inadequate cervical smears (adequacy being defined as the successful detection of cervical intraepithelial neoplasia and inadequacy as the failure to do so when disease was almost certainly present) was undertaken to determine whether indicators of effective cytological sampling could be identified. The association between inadequate smears and the absence of two types of normal epithelial cells (columnar cells of endocervical origin and immature metaplastic cells) was measured. A significant and substantial association was found between inadequate cervical smears and immature metaplastic cells and between inadequate smears and both types of cell. Endocervical cells alone were less likely to be found in inadequate than in adequate smears, but this association was not statistically significant.

Cervix Uteri↗

Renal adenocarcinoma with solitary metastasis to the contralateral adrenal gland: report of 2 cases and review of the literature.

We report 2 rare cases of renal adenocarcinoma with solitary metastasis to the contralateral adrenal gland, 1 recognized synchronously with the primary neoplasm and 1 found 15 years after nephrectomy. The latter case represents the longest reported interval between nephrectomy and treatment of a solitary contralateral adrenal metastasis of renal adenocarcinoma. Distinction of these metastatic tumors from primary adrenocortical carcinoma was facilitated by immunohistochemical markers. Twelve other reported cases of renal adenocarcinoma with solitary contralateral adrenal metastasis support aggressive surgical management of this lesion.

Adrenal Gland Neoplasms↗

Prognostic value of bronchoalveolar lavage in sarcoidosis: the critical influence of disease presentation.

There has been considerable disagreement about the prognostic value of bronchoalveolar lavage lymphocyte measurements in patients with sarcoidosis. This study looks at the influence of the type of disease presentation and the time since onset of symptoms on lavage fluid lymphocyte profiles in 99 patients studied at the time of their initial diagnosis. Patients who had an acute inflammatory onset of disease with erythema nodosum (n = 32) or acute uveitis (n = 17) almost invariably had high T lymphocyte helper:suppressor (TH:TS) ratios (mean 10.1, 95% confidence interval 7.7-12.5) and had a higher proportion of T lymphocytes in cells obtained at lavage (40%, 35-46%) than patients with a pulmonary presentation (n = 38) (TH:TS 2.9, 0.2-5.7; T lymphocytes 21%, 15-27%) or those studied after resolution of erythema nodosum (n = 12). The patients with recent erythema nodosum had the highest TH:TS ratios of any group (10.4, 8.1-12.7). Thus lavage T lymphocyte percentage and TH:TS are highest in patients with sarcoidosis studied soon after an acute onset with an inflammatory condition such as erythema nodosum or uveitis. Patients with an acute onset of sarcoidosis have a better prognosis than those with a more insidious presentation. The major influence of type of disease presentation and, in the case of patients with erythema nodosum, of time since onset of symptoms may in part explain why different centres have reported such diverse results regarding the value of bronchoalveolar lavage in predicting outcome in sarcoidosis. Studies where the case mix of patients includes a high proportion of patients with acute onset will not find a high TH:TS ratio or increased numbers or proportions of lavage lymphocytes to be indicators of a poor prognosis.

Acute Disease↗