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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 415 records · Page 23Linked to original sources
PubMed1991

An analysis of prognostic factors in stage III and IV Hodgkin's disease treated at a single centre with MVPP.

Two hundred and twenty seven patients with stage IIIA-IVB Hodgkin's disease have been treated at a single centre with MVPP chemotherapy followed by radiotherapy to sites of previously bulk disease. The median follow up is 58 months. 119 patients (52%) had stage IV disease. Overall complete remission (CR) rate was 72%. Discriminant analysis of factors predictive for complete remission showed that low albumin was the only independent factor that predicted a significantly lower chance of CR. Overall five year survival was 73%. A Cox multivariate analysis demonstrated that age greater than 40 years, stage IV disease, presence of bulk disease, low serum IgG and male sex to be variables which independently predicted poorer prognosis in terms of overall survival. Stage IV and lymphocyte depleted or unclassified histologies were independently predictive for poorer progression-free survival. Patient weight greater than 70 kg and stage IV disease were adverse prognostic factors for relapse free survival. Results are compared to other published multivariate analyses of prognostic factors in advanced Hodgkin's disease.

Adult↗
PubMed1991

Immunophenotypic study of lymphocyte predominance Hodgkin's disease.

An immunophenotypic study of 17 cases of diffuse lymphocyte predominance Hodgkin's disease and 20 cases of nodular lymphocyte predominance Hodgkin's disease, along with eight of mixed cellularity and five of nodular sclerosing Hodgkin's disease, is reported. The atypical cells in nodular lymphocyte predominance Hodgkin's disease showed only minor differences from the published consensus. However, the atypical cells in diffuse lymphocyte predominance Hodgkin's disease showed an immunophenotype which was commonly B-cell positive (59%), but in a minority of cases LeuM1 (24%) or epithelial membrane antigen (12%) positive; none of the cases was Ber-H2 positive. These results do not differ greatly from our findings in nodular lymphocyte predominance Hodgkin's disease, but do diverge from the published consensus for diffuse lymphocyte predominance Hodgkin's disease. The question as to whether morphology or immunophenotype should form the primary diagnostic criterion for the definition of lymphocyte predominance Hodgkin's disease is discussed.

Antigens, Differentiation, Myelomonocytic↗
PubMed1991

De novo 13q partial duplication identified by cytogenetic, biochemical and molecular approaches.

A 3.5-month-old female infant manifesting dysmorphic facies, developmental delay and failure to thrive was referred for cytogenetic evaluation. Peripheral lymphocytes revealed three chromosomally distinct cell lines: 46,XX/46,XX,10p+/47,XX,10p+,+mar. Dermal fibroblasts revealed only the 46,XX,10p+cell line. High resolution G-, R-, and Q-banding suggested that the extra chromosomal material (10p+) represented a duplication of the segment 13q14----13qter. Parental karyotypes were normal. As absolute identification of de novo chromosomal abnormalities, based solely on cytogenetic studies, is sometimes difficult, both biochemical and molecular approaches were undertaken to elucidate this abnormality in more detail. Dosage effects were examined using esterase D (localized to 13q14.1) and the DNA probes p1E8 and p9A7 (localized to 13q22 and 13q31/32, respectively). These studies suggested the presence of only 2 copies of esterase D, but 3 copies of both DNA probes, allowing identification of the breakpoint at 13q14.2.

Abnormalities, Multiple↗
PubMed1991

Is GIFT (gamete intrafallopian transfer) the best treatment for unexplained infertility?

OBJECTIVE: To compare the cumulative pregnancy rates after gamete intrafallopian transfer (GIFT) with the cumulative spontaneous pregnancy rates in couples with unexplained infertility. DESIGN: A contemporaneous study in a single group of patients. SETTING: Northern Regional Fertility Centre. SUBJECTS: 76 couples with unexplained infertility of more than 3 years duration. INTERVENTIONS: Successful pregnancies were recorded during at least 3 months before GIFT and up to 21 months after a maximum of three cycles of GIFT treatment. MAIN OUTCOME MEASURES: Pregnancy resulting in a live birth. RESULTS: Average monthly fecundability without treatment was 0.021 and after GIFT was 0.14 (P less than 0.001). This was reflected as a cumulative pregnancy rate of 52% after three cycles of GIFT and 30% after 24 months without treatment. CONCLUSIONS: The chance of having a baby after one cycle of GIFT is significantly greater than the chance in a spontaneous cycle. However, considering the cumulative pregnancy rates, we suggest that if GIFT is to be a realistic treatment option, it should be offered for more than one cycle.

Adult↗
PubMed1991

Gamete intrafallopian transfer (GIFT) compared with intrauterine insemination in the treatment of unexplained infertility.

OBJECTIVE: To compare GIFT, intrauterine insemination (IUI) with, and without, ovarian hyperstimulation in the treatment of unexplained infertility. DESIGN: Women randomly allocated to one of three treatment protocols. SETTING: Northern Regional Fertility Centre. SUBJECTS: 59 couples with unexplained infertility of more than 3 years duration. INTERVENTIONS: Three cycles of either GIFT, IUI after ovarian hyperstimulation or IUI in a spontaneous cycle. MAIN OUTCOME MEASURES: Pregnancy resulting in a live birth. RESULTS: Fecundabilities were 0.12 after GIFT, 0.018 after ovarian hyperstimulation and IUI, and 0.018 after IUI in a spontaneous cycle. The fecundability after IUI was no different from that which would be expected without treatment in these couples but fecundability was significantly better (P greater than 0.02) after GIFT. CONCLUSIONS: This trial does not support the use of IUI in the treatment of unexplained infertility but confirms the value of GIFT.

Adult↗
PubMed1991

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds as antioestrogens: characterization and mechanism of action.

In the female Sprague-Dawley rat uterus 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds exhibited a broad spectrum of antioestrogenic responses. For example 2,3,7,8-TCDD inhibited the 17 beta-oestradiol-induced uterine wet weight increase, peroxidase activity, oestrogen and progesterone receptor levels, epidermal growth factor (EGF) receptor binding, and EGF receptor and c-fos protooncogene mRNA levels. The aryl hydrocarbon (Ah) receptor was identified in the rat uterus and the antioestrogenic activities of TCDD and related compounds were structure-dependent. In parallel studies, the effects of TCDD as an antioestrogen in MCF-7 human breast cancer cells was also investigated. TCDD inhibited the 17 beta-oestradiol-induced proliferation of these cells and the secretion of the 34-, 52- and 160-kDa proteins. Treatment of MCF-7 cells with 1 nM [3H]-17 beta-oestradiol resulted in a rapid accumulation of nuclear oestrogen receptor (ER) complexes. Pretreatment of the cells with TCDD caused a rapid decrease in nuclear ER binding activity and immunoreactive protein; moreover, the structure-dependent potencies of TCDD and related compounds as antioestrogens were similar to their Ah receptor binding affinities. TCDD also caused a decrease in nuclear ER levels in wild-type Ah-responsive Hepa 1c1c7 cells but was inactive in Ah non-responsive mutant Hepa 1c1c7 cells. Moreover, in the wild-type cells, both actinomycin D and cycloheximide blocked the effects of TCDD. 6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) has previously been characterized as a TCDD antagonist in rodents and in transformed rodent cell lines. However, like TCDD, MCDF also exhibited a broad spectrum of antioestrogenic activities in both the female Sprague-Dawley rat uterus and MCF-7 cells. MCDF is relatively non-toxic compared to TCDD and is being investigated as a compound which may be clinically useful for the treatment of mammary cancer.

Animals↗
PubMed1991

Monocytoid B cell lymphoma.

The clinical, light microscopic, ultrastructural, immunocytochemical and cytogenetic features of a case of monocytoid B cell lymphoma were investigated. The tumour initially affected the cervical and supraclavicular nodes, but 33 months later affected the left parotid salivary gland. The patient had subclinical Sjögren's syndrome. The neoplastic cells showed characteristic morphological features and had peri- and interfollicular distribution in the node. Immunocytochemically the tumour cells were L26, 4KB5, MB2, CD19, CD20, CD22 and IgM/kappa positive. Prominent plasmablastic plasmacytoid differentiation was present in the recurrent tumour, suggesting an origin from post-follicular B cells. The lymphoma cells showed unusual cytogenetic abnormalities.

Adult↗
PubMed1991

Twelve cases of Ki-1 positive anaplastic large cell lymphoma of skin.

In seven of 12 cases of Ber-H2 (Ki-1) positive anaplastic large cell non-Hodgkin's lymphoma (Ki-1 ALCL) disease remained localised to skin, and in five there was extracutaneous spread. Four patients had histological evidence of pre-existing or coexisting mycosis fungoides, and three patients had a long standing history of eczema or ichthyosis. In two cases the presence of a T phenotype was shown in frozen sections, and in a further six cases a T phenotype was firmly established in paraffin wax sections. Four patients died less than one year after presentation (two with disseminated lymphoma; two from other causes); one died at five years with widespread lymphoma and the remaining seven cases were alive one to 14 1/2 years after presentation. Three of the four patients with associated mycosis fungoides had prolonged survival, contrary to the findings of previous reports which suggest secondary Ki-1 ALCL behaves aggressively. The recognition of these tumours is important because of their relatively good prognosis. The diagnosis can be readily substantiated immunohistochemically, using a simple panel of antibodies.

Adult↗
PubMed1991

The value of anticarcinoembryonic antigen, human milk factor globulin, and antikeratin antibodies in differentiating mesothelioma from lung carcinoma.

Monoclonal anticarcinoembryonic antigen (antiCEA), human milk factor globulin (HMFG2), and antikeratin antibodies were assessed for their value in the differential diagnosis of pleural mesothelioma (53 cases) and carcinoma of the lung (60 cases) in material from necropsies. In 40 of the cases pleural biopsies were also studied in the same manner. AntiCEA was found to be the best discriminating antibody for most types of mesothelioma; HMFG2 was slightly less valuable but a useful additional tool. Antikeratin was the least useful. For both antiCEA and HMFG2 antibodies, however, the proportion of carcinomas staining was smaller than in previous studies and this, combined with the positive staining of some mesotheliomas, reduces the value of the reactions in the individual case. Medical panels adjudicating compensation claims should not use these reactions as the sole criteria in deciding the origin of the tumours in these cases.

Antigens, Neoplasm↗
PubMed1991

A phase II study of combined methotrexate and teniposide infusions prior to reinduction therapy in relapsed childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.

Teniposide (VM-26) can increase intracellular methotrexate (MTX) and its polyglutamate derivatives in vitro and thus has the potential to improve the therapeutic index of regimens containing MTX. In this phase II study, children and adolescents with acute lymphoblastic leukemia (ALL) in first or second marrow relapse were randomly assigned to receive either simultaneous (n = 11) or sequential (n = 12) continuous infusions of MTX and VM-26 prior to reinduction. Infusions of VM-26 were begun 12 hours after completion of MTX infusion in the sequential group. Dosages were individually adjusted to maintain plasma concentration levels of 10 microns for MTX and 15 microns for VM-26; total infusion times were 24 and 72 hours, respectively. Significant toxicity in the first six patients who received the scheduled 72-hour VM-26 infusion (including one drug-related death) prompted a 50% reduction in infusion duration. The reduced dose was associated with similar but more manageable toxicity. Examination of bone marrow aspirates 10 days after therapy was begun showed one complete and two partial marrow remissions; a fourth patient who had an aplastic marrow on day 10 received no further chemotherapy and had a complete remission (CR) documented on day 31. There was no obvious clinical advantage associated with either infusion schedule, although small sample sizes preclude definitive conclusions. The 17% response rate to the MTX/VM-26 therapeutic window in patients with refractory disease suggests the need for further investigation to evaluate alternative schedules and concomitant therapy for this drug combination.

Adolescent↗
PubMed1991

Acute subdural hematoma: morbidity, mortality, and operative timing.

Traumatic acute subdural hematoma remains one of the most lethal of all head injuries. Since 1981, it has been strongly held that the critical factor in overall outcome from acute subdural hematoma is timing of operative intervention for clot removal; those operated on within 4 hours of injury may have mortality rates as low as 30% with functional survival rates as high as 65%. Data were reviewed for 1150 severely head-injured patients (Glasgow Coma Scale (GCS) scores 3 to 7) treated at a Level 1 trauma center between 1982 and 1987; 101 of these patients had acute subdural hematoma. Standard treatment protocol included aggressive prehospital resuscitation measures, rapid operative intervention, and aggressive postoperative control of intracranial pressure (ICP). The overall mortality rate was 66%, and 19% had functional recovery. The following variables statistically correlated (p less than 0.05) with outcome; motorcycle accident as a mechanism of injury, age over 65 years, admission GCS score of 3 or 4, and postoperative ICP greater than 45 mm Hg. The time from injury to operative evacuation of the acute subdural hematoma in regard to outcome morbidity and mortality was not statistically significant even when examined at hourly intervals although there were trends indicating that earlier surgery improved outcome. The findings of this study support the pathophysiological evidence that, in acute subdural hematoma, the extent of primary underlying brain injury is more important than the subdural clot itself in dictating outcome; therefore, the ability to control ICP is more critical to outcome than the absolute timing of subdural blood removal.

Accidental Falls↗
PubMed1991

Childhood immunisation advisory service for general practitioners.

A study of 270 general practitioners associated with the University of Sydney, Division of Family Medicine, was conducted to examine the need for a childhood immunisation advisory service. Forty-three per cent of respondents had deferred immunisation or altered the schedule of immunisation of children attending them over the previous month. The majority stated that an immunisation advisory service would be beneficial. The preferred option was a telephone service operating from 9 am to 5 pm.

Clinical Protocols↗
PubMed1991

Cocaine and indomethacin: fetal anuria, neonatal edema, and gastrointestinal bleeding.

A case is reported in which exposure to cocaine and indomethacin was associated with development of fetal anuria, anasarca, and neonatal gastrointestinal hemorrhage. Cocaine and indomethacin may act synergistically to adversely affect renal, cardiovascular, and platelet function. It may be prudent to obtain a drug history and urine screen for cocaine before instituting indomethacin therapy for preterm labor or polyhydramnios.

Adult↗
PubMed1991

Yaws infection in Tanna, Vanuatu 1989.

Yaws has been resurgent in the island of Tanna in southern Vanatu in the 1980's. Screening, conducted in 1988 and in 1989 during a mass treatment program identified a total of 464 clinical cases from the population of 20,200, a rate of 23 per thousand. Most of these (82%) were under 15 years of age. Serology was performed on 286 of which 23% were VDRL positive. Primary care services had been hampered in controlling yaws by difficulties with transport, isolation, community resistance and the lack of skilled personel to diagnose yaws and arrange prophylactic treatment. A mass screening and treatment program was implemented in 1989 with 91.8% coverage. This program was designed to work in the context of primary health care and thus has enhanced the relationship between the health services and local villagers. The program was successfully integrated with other health activities including health education, treatment of other diseases and vector control.

Age Factors↗
PubMed1991

Development of a protocol for early treatment of endemic meningitis in children in Vanuatu.

Meningitis is endemic in Vanuatu and other Pacific island countries and has a high case fatality rate. The incidence in the southern island of Tanna is especially high. This descriptive study of 64 cases in children (under 15 years) on that island was undertaken over a 21-month period from January 1988 to September 1989. Meningococcus was identified in 23 cases (36%) and Pneumococcus in 12 (19%). The age distribution showed a high rate in under 1 year olds. The symptoms of fever, convulsion and vomiting were most common. Bulging fontanelle (in children under 1 year), neck rigidity, and altered level of consciousness were the most frequent signs. These signs were as frequent in meningococcal as pneumococcal infections and were used to develop a simple protocol for use in primary care. Delay in treatment or referral because of patients seeking traditional medicine is a major problem yet to be overcome. Only a weak association between admissions with meningitis and underweight or crowding was found in this study.

Adolescent↗
PubMed1990

Cancer in the families of children with soft tissue sarcoma.

The cancer experience among 754 first-degree relatives (mothers, fathers, and siblings) of a population-based series of 177 children with soft tissue sarcoma is reported. The current study represents an extension of our earlier work in which the authors found an excess of breast cancer in the mothers of 143 of these children. There were 40 cancers among all first-degree relatives, compared with 24.82 expected (relative risk [RR] 1.61, P = 0.006). There was no excess in fathers, but an excess of borderline significance was seen in mothers (RR 1.67, P = 0.0545), and a significant excess in siblings (RR 4.55, P = 0.0002), mainly due to carcinoma of the breast and pediatric tumors. Results of a step forward Cox multivariate analysis identified three variables in the index child which were independently associated with high cancer risk in relatives, as follows: age younger than 24 months at diagnosis; histologic type, embryonal rhabdomyosarcoma or other and unspecified soft tissue sarcoma; and male sex. It was possible, therefore, to identify a subgroup of children whose relatives are at high risk of early onset cancer (RR in this group 10.14). The pattern of cancers is consistent with the Li-Fraumeni syndrome. The authors conclude that a marked proportion of childhood soft tissue sarcoma has a genetic basis.

Adolescent↗
PubMed1990

Structure-dependent induction of aryl hydrocarbon hydroxylase activity in C57BL/6 mice by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related congeners: mechanistic studies.

The time- and dose-dependent induction of murine hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities by five polychlorinated dibenzo-p-dioxin and dibenzofuran congeners showed that the order of induction potency was 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) greater than 2,3,7,8-tetrachlorodibenzofuran (TCDF) greater than 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD) greater than 1,2,3,7,8-pentachlorodibenzofuran (PCDF) greater than 2,3,7-trichlorodibenzo-p-dioxin (TrCDD). These structure-induction relationships were comparable to the structure-toxicity and competitive structure-receptor binding relationships previously reported for these compounds. However, using the corresponding radiolabeled congeners, the direct binding Kd values for dissociation of the cytosolic receptor-ligand complexes were 9.52, 7.96, 1.27, 3.10, and 8.31 nM for the 2,3,7,8-TCDD, 2,3,7,8-TCDF, 2,3,7-TrCDD, 1,2,3,7,8-PCDD, and 1,2,3,7,8-PCDF congeners and these data were clearly not structure dependent (i.e., similar to the structure-activity relationships). Some of the molecular properties for several radioligand-receptor complexes were similar; for example, the sedimentation coefficients for the cytosolic and nuclear receptor complexes varied from 8.8-10.4 S and 5.98-7.0 S, respectively, and the nuclear receptor complexes for all the radioligands eluted from a DNA-Sepharose column at salt concentrations of 0.27-0.29 M. Treatment of the mice with a maximum inducing dose of 2,3,7,8-[3H]TCDD resulted in a time-dependent formation of the nuclear receptor complex which was maximized between 16-24 hr and subsequently decreased up to 72 hr after initial exposure. In parallel studies, the nuclear receptor complex levels were determined 16 hr after treatment of the mice with different doses (2.25, 4.5, and 45 micrograms/kg) of all five radioligands. The results showed that at submaximal induction of the monooxygenase enzyme activities there was a linear correlation between the induced AHH or EROD activities (after 32 hr) and the corresponding nuclear receptor complex levels. It was also apparent from the data that the relative levels of nuclear receptor complex were structure dependent and this suggests that the transformation or activation of cytosolic receptor complexes may be a ligand structure-dependent process which correlates with the observed structure-activity relationships for 2,3,7,8-TCDD and related compounds.

Animals↗