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Biomedical subjects

E Blake

Publications and source records attributed to E Blake.

17 recordsLinked to original sources

Banking of human tissue for biomonitoring and exposure assessment: utility for environmental epidemiology and surveillance.

Human tissue banking could provide a tool to address a number of public health concerns. We can potentially use it to monitor trends in human exposures, serve as an early warning system for new environmental exposures, assess low-level exposures around hazardous waste and other point sources of pollutants, evaluate the effectiveness of regulatory programs, and study etiologies of diseases (e.g., childhood cancer and birth defects) that are likely to be related to the environment. This article discusses opportunities to establish human tissue banks in connection with pre-existing public health surveillance programs for cancer and adverse reproductive outcomes. This is a cost-effective way to conduct surveillance and enhances the ability to carry out epidemiologic studies. The article also discusses ethical issues that are particularly important for public health practice. One is the issue of risk communication and the need to explain risks in a way that provides people with the information they need to determine appropriate action on the individual and community levels. Second is the issue of environmental justice. We recommend early involvement of communities that are likely to be involved in tissue-banking projects and full explanation of individual and group social risks from their participation.

Cluster Analysis

[The clock test: a simple method to assess dementia].

AIM: to validate an easy and simple test to measure cognitive function: the clock drawing test. STUDY DESIGN: 138 hospitalized and free living elders (96 female, mean age 77.9 years) were studied. They were requested to draw a clock, using standardized instructions. The drawings were independently analyzed and scored by the authors. The Mini Mental State test was used as reference and the scores of both tests were correlated. RESULTS: there was a correlation of 0.73 between the scores of the clock drawing and Mini Mental State tests. Using a score of 7 points in tye clock drawing and 26 points in the Mini Mental State test as cut of points for the diagnosis of dementia, the former's sensitivity and specificity was 0.82 and 0.71 respectively. CONCLUSIONS: the clock drawing test appears as a simple and effective test for the initial assessment of cognitive functions in patients with suspected dementia.

Aged

Polymerase chain reaction (PCR) amplification and human leukocyte antigen (HLA)-DQ alpha oligonucleotide typing on biological evidence samples: casework experience.

The polymerase chain reaction (PCR) method of specific gene amplification was used in casework to synthesize millions of copies of the polymorphic second exon of the human leukocyte antigen (HLA)-DQ alpha (or DQA1) locus from a variety of evidence samples. The HLA-DQ alpha allelic variants in the amplified deoxyribonucleic acid (DNA) were determined in a rapid non-radioactive test by hybridization to sequence-specific oligonucleotide probes in both the dot-blot and reverse dot-blot formats. This genetic typing system has been subjected to blind proficiency testing; the performance of this test in the analysis of experimentally mixed samples was also evaluated. As of August 1990, over 250 cases have been tested and more than 2000 individual evidence (bloodstains, semen stains, individual hairs, bone fragments, and tissue sections) and reference samples have been analyzed. The first 198 of these cases are summarized in this paper; in 65% of the cases with conclusive results a suspect was included, and in 35%, all suspects were excluded. Individual cases as well as some of the general issues relating to forensic science analysis and this genetic typing system are discussed. The high rate of exclusion reported here combined with the ability of PCR to type old evidence samples suggests the relevance of this genetic test for postconviction review; two cases in which the convicted suspect was excluded are discussed.

Adolescent

Analysis of genetic markers in forensic DNA samples using the polymerase chain reaction.

The ability to extract and type DNA from forensic evidentiary samples has revolutionized the field of forensic serology. Previously, genetic marker typing was limited to the analysis of blood group markers and soluble polymorphic protein markers. Because the number of suitable markers expressed in particular fluids and tissues is relatively small, and because mixtures of fluids cannot be separated for conventional genetic marker typing, a suspect frequently cannot be included or excluded as a fluid donor in a case. However, the development of methods to extract DNA from virtually all biological specimens has greatly expanded the potential for individual identification. Of particular importance was the ability to extract mixtures of sperm cells and epithelial cells found in sexual assault cases such that the DNA from the sperm cells could be typed independently of the DNA from the victim's epithelial cells. Restriction fragment length polymorphism (RFLP) analysis was the first DNA-based method applied to problems of individual identification. This method, while powerful in its ability to differentiate individuals, is limited by the quantity and quality of DNA required for an unambiguous result and by the amount of time it takes to obtain a result. Despite these limitations, several laboratories are using RFLP analysis successfully for the detection of polymorphisms in forensic DNA case samples. While the field of forensic serology was being revolutionized by the prospect of DNA analysis, the field of molecular biology was being revolutionized by the invention of the polymerase chain reaction (PCR), which ultimately has had an impact on every area of biological science. The PCR DNA amplification technology is ideally suited for the analysis of forensic DNA samples in that it is sensitive and rapid and not as limited by the quality of DNA as the RFLP method. The focus of this article is the use of the PCR for typing genetic markers, and we will address specifically the special considerations that arise from applying DNA amplification and typing technology to forensic materials.

DNA

HLA-DQ alpha allele and genotype frequencies in various human populations, determined by using enzymatic amplification and oligonucleotide probes.

Allele and genotype frequencies at the HLA-DQ alpha locus have been determined by the use of polymerase chain reaction (PCR) amplification and nonradioactive oligonucleotide probes. The probes define six alleles and 21 genotypes in a dot-blot format. A total of over 1,400 individuals from 11 populations has been typed by two different laboratories using this method. In contrast to some variable-number-of-tandem-repeat markers that have been used for identity determination, DQ alpha genotype frequencies do not deviate significantly from Hardy-Weinberg equilibrium in all populations studied. The distribution of alleles varies significantly between most of these populations. In Caucasians, the allele frequencies range from 4.3% to 28.5%. In this population, the power of discrimination is .94, and, for paternity determination, the power of exclusion is .642. These population data will allow the use of the HLA-DQ alpha marker in paternity determination, the analysis of individual identity in forensic samples, and anthropological studies.

Alleles

Comparison of single dose netilmicin with a five-day course of co-trimoxazole for uncomplicated urinary tract infections.

Women with uncomplicated urinary tract infections were randomly allocated to either a single 150 mg intramuscular dose of netilmicin or a standard five-day course of oral co-trimoxazole. Twenty-one of 22 were cured with netilmicin and all 20 with co-trimoxazole. No patient treated with netilmicin developed any side effects or obvious toxicity. Following co-trimoxazole one woman developed a severe skin rash and another nausea. Netilmicin is another drug which is highly effective when used in a single dose regimen for the treatment of uncomplicated urinary tract infections. There are many advantages of this approach to the management of a common clinical problem.

Administration, Oral

Single dose doxycycline, cefuroxime and pivmecillinam for treatment of bacterial cystitis.

There is now considerable evidence showing the benefits of single dose antibacterial treatment for uncomplicated urinary tract infections. If single dose therapy is to become widely used it is necessary to clarify the minimum effective dose of the most efficient drugs. This paper reports three trials in women presenting in general practice with bacterial cystitis. In each trial the patients were randomly allocated to either a five day course of oral co-trimoxazole (CTM) or to doxycycline 300 mg orally, cefuroxime 1.5 g intramuscularly or pivmecillinam 600 mg orally. Thirty-eight of 45 patients treated with doxycycline were cured, compared with 44 or 45 treated with CTM. Fourteen of 20 women given cefuroxime were cured, compared with 19 of 20 prescribed CTM. Twenty-three of 30 women treated with pivmecillinam were cured, compared with all 30 given CTM. None of these three drugs, when administered as a single dose, was as effective as a single 1.92 g or 2.88 g dose of CTM used in our previous studies in domiciliary practice. These studies confirmed, however, that single dose therapy was well tolerated, preferred by the patients and side effects were minimal.

Administration, Oral

A simple test for detecting pyuria.

Pyuria indicates inflammation within the urinary tract. A test strip, Cytur-Test, was used to detect a significant number of white cells in 100 consecutive urine samples and compared with the quantitative white cell concentration. The test was simple, rapid, easy to read, the false positive rate was low and the false negative rate was acceptable. In screening patients for urinary tract disease the Cytur-Test would be particularly useful if combined with tests for protein, blood and glucose.

False Negative Reactions

Serum and urine concentrations of cefoperazone in severe chronic renal failure.

Two studies evaluating the efficacy of cefoperazone in patients with chronic renal failure are described. In study A, 10 patients with severe chronic renal failure were given 1 g of cefoperazone intravenously over 3 minutes. The mean serum cefoperazone concentration at 30 minutes was 119.3 +/- 15.7 microgram/ml, and at 6 hours was 35.9 +/- 5.7 micrograms/ml. The mean serum half-life using the method of least squares was 6.6 +/- 1.15 hours (range, 2.5 to 15.1). The mean half-life from 2 hours onwards was 12.2 +/- 3.51 hours (range, 2.3 to 42.9). The mean peak urinary concentration of cefoperazone was 192 microgram/ml with a very wide individual range of 20 to 920 microgram/ml which was reached 0.5 to 9 hours after injection. In study B, 8 patients with chronic renal failure were treated with 1 to 2 g of cefoperazone intravenously every 12 hours for 5 to 14 days for complicated urinary tract infections. Serum and urine concentrations of cefoperazone were measured 6 hours after each morning dose. The mean 6-hour serum and urine concentrations of cefoperazone for the 4 patients treated with 2 g daily were 63 +/- 11.7 and 87 +/- 11.1 microgram/ml, respectively. The corresponding values for the 4 patients treated with 4 g daily were 106 +/- 20 and 258 +/- 32 microgram/ml. No drug accumulation occurred in any patient. No deterioration in renal function was noted. In conclusion, cefoperazone promises to be an effective and safe broad-spectrum antibiotic for patients with all degrees of renal function impairment. A dosage schedule of 2 to 4 g daily will not lead to significant drug accumulation in the presence of severe renal failure.

Adult

Cefoperazone in the treatment of severe or complicated infections.

We report the use of cefoperazone in 62 cases of serious infection, most of which occurred in patients with renal impairment. 43 severe or complicated urinary tract infections, 11 cases of pneumonia and 8 with other severe sepsis were treated with cefoperazone 1 to 2 g twice daily usually for 5 to 10 days. Of the patients with urinary tract infection, all who were symptomatic showed a rapid clinical response; 26 (61%) were cured including 11 of 16 with chronic renal failure; 12 relapsed and 5 were reinfected with a different pathogen. All of these patients were infected by organisms sensitive to cefoperazone by disc testing but in 5 of those who relapsed the cefoperazone MIC was in fact greater than or equal to 50 microgram/ml. Ten of 11 cases with radiologically confirmed pneumonia were cured with cefoperazone. 7 episodes of pneumonia were in patients with end-stage chronic renal failure (6 were on dialysis) and 1 was in a patient with acute renal failure. Seven of 8 cases with severe sepsis were cured with cefoperazone. 1 patient was withdrawn from the study when acute bronchospasm followed a 2 g intravenous dose. 2 of the successfully treated patients had functioning renal transplants, 2 of 3 with severe chronic renal failure were on dialysis and 1 had acute renal failure. Side effects included minor disturbances of liver function in 6 patients (11%), diarrhoea in 7 (13%) and marked alcohol intolerance in one, 4 patients with chronic renal failure developed a coagulation disorder which was corrected with vitamin K. None of the patients showed deterioration in renal function while receiving cefoperazone. Cefoperazone promises to be an effective drug for the treatment of a wide spectrum of severe infections in hospitalised patients including those with impaired renal function.

Adolescent

Treatment of uncomplicated urinary tract infections with a single dose of co-trimoxazole.

Sixty-four women with an uncomplicated urinary tract infection were randomly allocated to receive treatment with either an 0.96 g, 1.92 g or 2.88 g single oral dose of co-trimoxazole or a conventional five-day course of co-trimoxazole. The success of each group was comparable although it is suggested that a single dose should be at least 1.92 g (four tablets Septrin or Bactrim). This study confirmed previous work that single dose therapy was effective and well tolerated, preferred by the patients and side effects were minimal. This approach to treatment should be strongly encouraged.

Adolescent

Netilmicin in the treatment of severe or complicated urinary tract infections.

Netilmicin is a new aminoglycoside antibiotic with pharmacological similarities to gentamicin, tobramycin and sisomicin. Fourteen of 15 patients with a severe or complicated urinary tract infection were cured by treatment with a seven day course of netilmicin. In one patient the infecting organism was not eradicated. No significant side effects were noted and no ototoxicity was detected. Four patients had a significant, but reversible, deterioration in renal function as defined by an increase in the plasma creatinine of 0.03 mmol/l or greater. Work in experimental animals has shown netilmicin to be significantly less ototoxic and nephrotoxic than other clinically available aminoglycosides. If this finding is confirmed in large-scale comparative trials in man, netilmicin should prove a most useful and effective new antibiotic for the treatment of severe gram-negative sepsis.

Adult

Quantitative studies of translymphnodal passage of tumour cells naturally disseminated from a non immunogenic murine squamous carcinoma.

A squamous cell carcinoma of spontaneous orgin in a WHT/Ht mouse was used to study the frequency with which the regional axillary lymph nodes draining subcutaneous or intradermal tumours gave rise to tumours after their isogeneic transplantation as whole nodes. This frequency (similar to 40%) was found not to vary significantly with the size or duration of the tumour drained and not to be increased by coincident infective, traumatic or antigenic stimuli acting at the tumour site or in adjacent tissue. Because tumour growth occurred in only 2/55 (4%) nodes which were left in situ in mice whose tumours were radically excised, it was concluded that tumour forming node transplants reflected a small and limited content (estimated to be about 13) of transnodally passing tumour cells destined to pass on to the blood; separate experiments showed that tumour cells reaching the blood survived for only a few hours. Nodes from tumour-excised mice gave rise to tumours as frequently when autografted as when isografted to mice with no previous expose to the tumour. A review of the finding reported here and of previous quantitative data for this system enabled us to exclude any implication of anti-tumour immunity from our interpretation of the results of the experiments.

Animals

The effect of lethally irradiated cells on the transplantability of murine tumours.

Fully quantitative isogeneic transplantation assays of viable (V) cells of a CBA carcinoma showed that the relationship between log inoculum and frequency of tumour "takes" accorded strictly with a Poisson distribution and indicated that 6900 cells were required for 50% takes (TD50). Addition of 10(5) lethally irradiated (LI) cells of the same tumour to the inocula reduced the TD50 to about 4 cells, yet the Poisson relationship was retained. From this and other data it is concluded that LI cells act by increasing the proportion of viable cells which contribute to tumour initiation; there was no evidence that LI cells affected the rate of proliferation of viable cells. The ability of non-homologous LI cells to reduce the TD50 was widely variable, but LI cells of one allografted tumour were almost as effective as homologous LI cells. Lethally irradiated cells did not assist the "take" of allografted viable tumour cells. Histological comparison revealed no difference of the tissue reaction to inocula of viable and LI cells, and it is questioned whether radiation induced lysis of these latter cells is required for their effect on viable cells. Evidence relating to a hypothesis that viable cells interact with one another as they do with lethally irradiated cells was conflicting.

Air