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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 19 recordsLinked to original sources
PubMed1992

Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498.

The treatment of acute myeloid leukemia (AML) in children with Down's syndrome (DS) has engendered considerable controversy. Because of the concerns for toxicity and increased rate of infections, treatment approaches varied considerably in the past with mixed results. However, experience on the recently completed Pediatric Oncology Group (POG) 8498 AML study suggests that DS children with AML constitute a distinct subgroup that responds well to therapy. Twelve of 285 children on POG 8498 (protocol for newly diagnosed AML) had DS. Children with DS and AML were predominantly male (9 of 12) and were quite younger at diagnosis (< 24 months in 10). The white blood cell count was less than 50 x 10(3)/microL in all 12 and French-American-British types M6 and M7 were frequent (5 of 12). An abnormal cytogenetic marker, in addition to constitutional trisomy 21, was present in 9 of 12 and involved chromosome 8 in 4 of 9. All cases studied (n = 5) were positive for myeloid cell surface markers (CD33, CD13, or CD11b) and, interestingly, were also positive for the CD7 antigen. Chemotherapy included daunorubicin, cytarabine (Ara-C), and 6-thioguanine for remission induction and featured high-dose Ara-C (3 g/m2 per dose) with or without L-asparaginase early in remission. Compared with children without DS, children with DS had a superior event-free survival (EFS at 4 years 100% v 28% +/- 6.2%; P = .003). The EFS remained superior even when compared with non-DS children less than 2 years of age with a white blood cell count less than 10 x 100,000/microL (100% v 48% +/- 17.3%; P = .01).

Acute Disease↗
PubMed1992

Randomised trial of cardiotocography alone or with ST waveform analysis for intrapartum monitoring.

It is possible to record the fetal electrocardiographic waveform (ECG) from the scalp electrode used in labour for detection of fetal heart rate. Animal and observational studies of changes in the ST waveform of the ECG during hypoxia suggest that a combination of heart rate and ST waveform analysis might improve the predictive value of intrapartum monitoring. In a randomised trial, we have studied intervention rates and neonatal outcome for high-risk labours monitored either by conventional cardiotocography (CTG) or by ST waveform analysis plus CTG. 1200 women with pregnancy of at least 34 weeks' gestation were assigned to the groups when the decision to apply a fetal scalp electrode was made. Neonatal outcome was assessed by umbilical-cord blood gas analysis, Apgar scores, resuscitation needed, and postnatal course. All recordings were retrospectively viewed by an observer unaware of clinical details to check adherence to the trial protocol. The addition of ST waveform monitoring to CTG substantially reduced the proportion of deliveries for fetal distress (ST + CTG 27/615 vs CTG 58/606; p less than 0.001). The groups did not differ in rate of operative delivery for other reasons, incidence of asphyxia at birth, or neonatal outcome. Metabolic acidosis and low 5 min Apgar scores were less common in the ST + CTG than the CTG group, but not significantly so. The only case of birth asphyxia in the ST + CTG group was identified by both heart rate and ST changes. The review of recordings showed that the reduction in intervention rate was among cases with CTG patterns classified as normal or intermediate, whereas there was no difference in intervention rates among cases with abnormal recordings. Our findings confirm that ST waveform analysis discriminates CTG changes in labour and that our protocol for interpretation is safe. Further randomised studies are warranted.

Adult↗
PubMed1992

Relationship between immune response to melanoma vaccine immunization and clinical outcome in stage II malignant melanoma.

The authors investigated whether there was a relationship between the induction of a delayed-type hypersensitivity (DTH) response to melanoma vaccine immunization and disease recurrence. They studied prospectively 94 evaluable patients with surgically resected Stage II malignant melanoma who were immunized to a partially purified, polyvalent, melanoma antigen vaccine. The DTH response to skin tests to the vaccine was measured before treatment and at the fourth vaccine immunization. Vaccine treatment induced a strong DTH response in 29 (31%) patients, an intermediate response in 24 (25%), and no response in 41 (44%). The median disease-free survival (DFS) of patients with a strong, intermediate, and no DTH response to vaccine immunization was more than 72 months, 24 months, and 15 months, respectively. The relationship between an increase in the DTH response and a prolonged DFS was statistically significant (P = 0.02); clinically meaningful (the median DFS of patients with a strong DTH response was 4.7 years longer than that of nonresponders); and, by multivariate analysis, independent of disease severity or overall immune competence. These findings suggest, but do not prove, that vaccine treatment can slow the progression of melanoma in some patients.

Adult↗
PubMed1992

Evaluation of CHIP (iproplatin) in recurrent pediatric malignant solid tumors. A phase II study (Pediatric Oncology Group).

CHIP (325 mg/M2), a second generation cisplatin derivative, was administered intravenously every 3 weeks to 85 pediatric patients with recurrent sarcomas (19), osteosarcomas (20), neuroblastoma (23), germ cell tumors (10), and other malignant tumors (7). Thirty-eight of them had been previously exposed to cisplatin. Partial remissions were only observed in 3 of 23 (13% SE = 7%) patients having neuroblastoma. Severe thrombocytopenia (65%) and neutropenia (35%) were the dose limiting factors.

Adolescent↗
PubMed1992

Interleukin-1: the principal osteolytic cytokine produced by keratocysts.

Fragments of keratocysts removed at operation were maintained in explant culture and the media were assayed for the biological activity of the potent osteolytic cytokines--interleukin (IL)-1, interleukin (IL)-6 and tumour necrosis factor (TNF). Media were also assayed for their ability to stimulate bone resorption. All six cysts examined released IL-1 and IL-6 bioactivity but TNF bioactivity was unmeasurable. Dialysed cyst media stimulated bone resorption and this could be completely inhibited by a monospecific antibody which neutralized IL-1 alpha and IL-1 beta. Immunohistochemical staining of cryostat sections of keratocysts revealed the presence of IL-1 alpha and IL-6 in cyst epithelial cells but not in other cell types. Sections did not react with antibodies to IL-1 beta or TNF. It is therefore proposed that IL-1 alpha is the major osteolytic cytokine produced by keratocysts and that IL-6 and IL-1 may contribute to keratocyst growth by promoting epithelial cell proliferation and bone resorption, respectively.

Adult↗
PubMed1992

6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) as an antiestrogen in human and rodent cancer cell lines: evidence for the role of the Ah receptor.

6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) is a relatively nontoxic analog of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Treatment of aryl hydrocarbon (Ah)-responsive MCF-7 human breast cancer cells with 100 nM MCDF resulted in the inhibition of 17 beta-estradiol-induced proliferation and the secretion of the 34-, 52-, and 160-kDa proteins. After treatment of the cells with 17 beta-[3H]estradiol, 100 nM of MCDF caused a decrease in the accumulation of the radiolabeled nuclear estrogen receptor (ER) complex in these cells. In parallel experiments, the antiestrogenic effects of MCDF were also determined in Ah-responsive wild-type Hepa 1c1c7 cells and Ah-nonresponsive class 1 and class 2 mutant cells. Treatment of the wild-type cells with 17 beta-[3H]estradiol and 100 nM MCDF caused a decrease in the accumulation of radiolabeled nuclear ER complex in these cells whereas no significant effects were observed in the mutant cells as determined by velocity sedimentation analysis. Comparable results were obtained using ER antibodies to measure the decrease in immunoreactive nuclear ER. In addition, both actinomycin D and cycloheximide inhibited the MCDF-mediated decrease of nuclear ER levels in the Hepa 1c1c7 wild-type cells. Although 100 nM MCDF did not induce cytochrome P-450-dependent monooxygenases in the MCF-7 or Hepa 1c1c7 cell lines, incubation of nuclear extracts from the MCF-7 cells treated with 100 nM MCDF with a synthetic consensus dioxin responsive element (an oligonucleotide duplex of 26 bases) gave a retarded band in a gel-retardation assay. The data suggest that the antiestrogenic effects of MCDF does not require the induction of the CYP1A1 gene expression but may involve the induction of other genes.

Animals↗
PubMed1992

Retinal speed gradients and the perception of surface slant.

Previous work has demonstrated a difference in human sensitivity to compressive and shearing speed gradients. This raises the possibility that the ability to estimate the slant of a surface may vary with its direction of tilt. No such variance was found here, which may indicate that slant estimation depends upon deformation rather than upon compression or shear.

Humans↗
PubMed1992

The conservative management of osteoradionecrosis of the mandible with ultrasound therapy.

A regimen of ultrasound with local debridement and metronidazole has proved to be an effective and practicable treatment for osteoradionecrosis, achieving healing in 10/21 (48%) cases without the need for surgery or sophisticated technology. Nine further patients were successfully treated by covering the preserved mandible with a local intra-oral flap. Only 2 patients required mandibular resection with reconstruction. An ultrasound programme of 1 watt/cm2, 3 mega Hz. pulsed 1:4, 15 min a day for 60 days would seem to be optimum. However, a range of dosage needs to be further explored for inducing neovascularity and neocellularity in the irradiated tissues.

Brachytherapy↗
PubMed1992

Prevalence of post-traumatic stress disorder in patients with chronic idiopathic facial pain.

34 patients with chronic idiopathic orofacial pain were assessed by a structured clinical interview for diagnosis of mental disorders according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-III-R). Five (15%) had a history of post traumatic stress disorder (PTSD) which coincided with the pain onset. The majority of these PTSD sufferers also had a personality disorder. The implications of these findings in the diagnosis and management of post-traumatic chronic TMJ pain syndromes is discussed.

Adult↗
PubMed1992

Association of schizophrenia and partial trisomy of chromosome 5p. A case report.

A normal balanced chromosome 5 translocation carrier (5:14) (p14.1; q32.3) produced one offspring with a 5p deletion syndrome (cri du chat syndrome) and two with a partial trisomy (one with schizophrenia and the other with refractory epilepsy). We had hypothesized that the translocation might be complex and involve 5q, overlapping with a schizophrenia associated area described by Bassett et al., (1988). Cytogenetic study, however, indicated that there was no overlap in the involved chromosome 5 trisomy for this individual with schizophrenia and the trisomic region previously described. The probands with the trisomy and the cytogenetic findings are described in this report. Alternative interpretations are suggested to explain the association of schizophrenia and chromosomal abnormalities.

Adolescent↗
PubMed1992

The impact of research findings on current practice in relieving postpartum perineal pain in a large district general hospital.

In order to study the impact of research findings on current clinical practice 100 members of midwifery and medical staff of a large district general hospital were surveyed regarding their treatment of postpartum perineal pain. Of the 76 who responded only 20 (26%) referred to research findings to support their clinical practice and in only one case was the research appropriate to the population in question. Important research findings were not applied, while the majority of the reported practice was not research-based. Research-based practice is not only the responsibility of the individual clinician but also of those at educational and management levels. Local strategies should be developed and resources made available to facilitate research utilisation and implementation.

Clinical Nursing Research↗
PubMed1992

Immunohistological examination of the inter- and intracellular distribution of O6-alkylguanine DNA-alkyltransferase in human liver and melanoma.

The tissue and cellular distribution of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) is an important question in relation to the response of tumour and normal tissues to chemotherapeutic regimes employing alkylating agents such as methyltriazenes and nitrosoureas. In order to examine this issue by immunostaining, we have raised a rabbit antiserum to apparently pure recombinant human enzyme. The antiserum is highly specific and sensitive, detecting a band at 24 kDa on western blots of crude extracts of ATase-expressing human lymphoblastoid cells, liver and melanoma. Adjacent sections of acetone or formalin fixed normal human liver and subcutaneous malignant melanoma were reacted with preimmune serum or antiserum and an immunoperoxidase detection system with silver enhancement was used to locate binding of the primary antibody to the antigen. In sections reacted with preimmune serum or with antigen-preadsorbed antiserum, only faint cytoplasmic and little or no nuclear staining was seen. In contrast, using antiserum, the reaction in positively staining cells was very intense and predominantly nuclear. In the liver, there was interindividual variation in the cellular distribution of reaction with staining present in all discernable cell types in most samples but confined to the hepatocytes and bile duct epithelial cells in others. In the melanoma sections, all discernable cell types showed mainly nuclear staining: the intensity of staining varied between tissue samples and there was evidence of a range of intermediate staining intensities with some melanoma cells showing no detectable reaction.

Biopsy↗
PubMed1992

Sarcomas in north west England: III. Survival.

Survival data on a population-based series of bone, soft tissue and visceral sarcomas diagnosed in the North West of England between 1982-84 and subjected to histopathological peer review are presented. Five-year crude survival for all cases was 34%. Survival in males and females did not differ significantly (P = 0.6, 5-year survival 32% vs 36%) but was markedly worse for patients diagnosed over the median age of 60 years, even when allowance was made for underlying mortality (P = 0.03, 34% vs 44%). Five-year survival rates for the major site groups were: bone 44%; soft tissues of head, neck and trunk 36%; soft tissues of extremities 35%; female genital tract 35%; retroperitoneum 15%; gastro-intestinal tract 13%. Analysis by the major histological types revealed the following survival rates: leiomyosarcoma--female genital tract 25%, gastro-intestinal tract 14%, non-visceral soft tissue 21%; malignant fibrous histiocytoma of soft tissue 29%; liposarcoma 52%; osteosarcoma of bone 46%; and chondrosarcoma of bone 50%.

Adult↗
PubMed1992

In vivo derived HIV-1 nef gene products are heterogeneous and lack detectable nucleotide binding activity.

Multiple HIV-1 nef genes were cloned from lymphocyte DNA of asymptomatic seropositive individuals by polymerase chain reaction (PCR). Sequence analysis of these clones revealed a unique set of nef variants with premature terminations (PCRnef 1 and 6), mutations at sites of potential posttranslational modification (PCRnef 2 and 3) and deletions. In common with laboratory isolates of nef, strong sequence conservation was observed in the central domain of nef and in the myristylation target sequence, with variable domains toward the N- and C-termini of the molecule. The biochemical function of nef remains elusive however, as the products of these genes cloned into a bacterial expression system failed to reveal any nucleotide binding activity.

Amino Acid Sequence↗
PubMed1992

Reasons for encounter and diagnosed health problems: convergence between doctors and patients.

This study of 521 encounters in 25 urban general practices in Australia, compares both patient and doctor reported reasons for encounter (RFE) and diagnoses. Although doctors and their patients generally agreed on the overall distribution of RFE and diagnoses that arose, there was disagreement in at least 30% of paired comparisons within individual encounters. There was better agreement for RFE than for diagnoses. This may have been partly due to differences in the classification systems used. However, it suggests that diagnoses recalled by patients at later household interview are at best only a rough approximation of the diagnoses recorded by the doctor. These findings are important both for patient care and for the conduct of general practice morbidity research.

Attitude of Health Personnel↗