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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 289 records · Page 16Linked to original sources
PubMed1995

Autologous blood stem cell transplantation for haematological malignancy: treatment-related mortality of 2%.

BACKGROUND: Lengthy remission or cure has remained elusive for patients with many of the common haematological malignancies. Thus high dose chemotherapy followed by autologous haemopoietic stem cell transplantation is being increasingly utilised in these diseases. AIM: To assess the safety of high dose chemotherapy and autologous stem cell transplantation in haematological malignancy. METHODS: Forty-eight patients with haematological malignancy were given high dose chemotherapy followed by an infusion of previously cryopreserved autologous peripheral blood stem cells with (patients with acute myeloid leukaemia [AML]) or without (patients with acute lymphoblastic leukaemia [ALL], chronic myeloid leukaemia, non-Hodgkin's lymphoma, Hodgkin's disease and myeloma) autologous bone marrow. RESULTS: All patients except one had sustained engraftment. The median (range) number of days to attain a neutrophil count of 0.5 x 10(9)/L was 12 (10-42) and a platelet count of 20 x 10(9)/L unsupported by platelet transfusions was 15 (eight to 155). Other than oropharyngeal mucositis and febrile neutropenia, morbidity was low. Two patients had haemorrhagic cystitis, one hepatic veno-occlusive disease and one interstitial pneumonitis; all resolved. The treatment-related mortality was 2%--a single patient with AML died of failure of sustained engraftment. CONCLUSIONS: Autologous blood stem cell transplantation to support high dose chemotherapy is a relatively safe procedure and its efficacy is currently being explored in a wide range of haematological malignancies.

Acute Disease↗
PubMed1995

Inflammatory pseudotumour of lymph nodes.

AIM: To describe the clinical, histological and immunohistochemical features in four cases of an uncommon benign lymph node lesion which may mimic a neoplastic process. METHODS: Four cases of inflammatory pseudotumour of lymph nodes were studied using conventional staining (haematoxylin and eosin, PAS, Gordon and Sweets reticulin stain, and the Ziehl-Neelsen stain) and with immunohistochemical techniques using a variety of antibodies (CD3, L26, CD15, CD21, CD30, KP1, MAC 387, vimentin, alpha SMA, HHF-35, D33, CD34, and S100). RESULTS: The lesion comprises a proliferation of spindle cells expanding the connective tissue framework of lymph nodes and is associated with a plasma cell and small lymphocyte infiltrate. There are variable numbers of macrophages, neutrophils and eosinophils, and varying degrees of fibrosis. Vascular changes are common but vary in degree and type. CONCLUSIONS: Inflammatory pseudotumour of lymph nodes is an uncommon benign reaction pattern which may be misdiagnosed as a neoplastic or even a malignant process. Increased awareness of its histological features should help prevent such misdiagnoses.

Adult↗
PubMed1995

Audit of tumour histopathology reviewed by a regional oncology centre.

AIMS: To analyse the diagnostic differences in reporting tumour histopathology between a district general hospital and a regional oncology centre. METHODS: Tumour histopathology reports (n = 227) extracted from Bolton General Hospital files between 1988 and 1992 were compared with the corresponding Christie Hospital (oncology centre) reports, the same material having been seen at both hospitals. RESULTS: Diagnostic agreement existed in 77% of all cases. The incidence of major discrepancies was 8.37%. Of the diagnoses, 19 (36%) cases involved major discrepancies and 34 (64%) cases minor discrepancies. Most discrepancies occurred in the lymphoma group and involved subclassification of Hodgkin's and non-Hodgkin's lymphoma. Ki1 anaplastic large cell lymphoma and T cell rich B cell lymphoma were problematic diagnoses. The correct grading of follicle centre cell lymphomas using the Kiel classification was another problem area. In 19 cases certain aspects of immunohistochemistry produced discrepancies. In one case an incorrect diagnosis was made at the oncology centre and in another both centres gave an incorrect diagnosis. CONCLUSIONS: Areas of diagnostic difficulty mainly involve the subclassification of lymphomas. Review of tumour pathology by experts is recommended, at least in certain categories, to ensure correct diagnosis and uniformity in subclassification of tumours.

Cancer Care Facilities↗
PubMed1995

Family accommodation in obsessive-compulsive disorder.

OBJECTIVE: Family accommodation of patients with obsessive-compulsive disorder, i.e., participation in symptoms and modification of personal and family routines, was assessed in relation to family stress, functioning, and attitudes toward the patient. METHOD: Primary caretakers for 34 patients with obsessive-compulsive disorder were interviewed to assess the nature and frequency of accommodating behaviors. The caretakers also completed several measures of family functioning. RESULTS: Of the 34 spouses or parents, 30 (88.2%) reported accommodating the patient. Family accommodation correlated with poor family functioning, rejecting attitudes toward the patient, and several types of family stress. CONCLUSIONS: Family accommodation of patients with obsessive-compulsive disorder was associated with global family dysfunction and stress. This study suggests that families' efforts to accommodate patients may be intended to reduce patient anxiety or anger directed at relatives.

Adult↗
PubMed1994

Carcinomatous meningitis in patients with breast cancer. An aggressive disease variant.

BACKGROUND: Carcinomatous meningitis is a rare and often devastating complication in patients with breast cancer, and the treatment is controversial. METHODS: A retrospective analysis of 35 patients with carcinomatous meningitis from breast cancer was performed to define the biology of the disease and to guide treatment. RESULTS: An aggressive variant of breast cancer was revealed: meningeal metastasis complicates less than 3.5% of cases of metastatic breast carcinoma. Sixty-seven percent of these patients had tumors that were lobular or combined lobular/ductal histology; the median intervals from primary treatment to disease recurrence and from recurrence to death were 10.9 and 15 months, respectively. The median survival after diagnosis of carcinomatous meningitis was 77 days. The most significant prognostic factor was the Karnofsky performance status (KP) at presentation of meningeal disease. Patients with a KP greater or equal to 70 survived a median of 313 days, whereas those with a KP of 60 or less survived for a median of 36 days (P = 0.0002). In addition, there was a trend suggesting that the response 2 weeks after treatment was initiated, correlated with survival. CONCLUSIONS: Carcinomatous meningitis from breast carcinoma is an aggressive metastatic complication with a poor prognosis. The authors suggest that patients with a poor KP (< 70) should be treated symptomatically and those with a good KP (> or = 70) should receive more aggressive treatment. The patients' survival in this study compared well with other reports, and yet, only one patient was treated with intraventricular chemotherapy. Therefore, these data question the superiority of intraventricular treatment versus other modalities.

Adult↗
PubMed1994

Leukemia, lymphoma, and related disorders in families of children diagnosed with Wilms' tumor.

Leukemias and lymphomas occurring in a series of families with Wilms' tumor (WT) are described. One surviving case developed a large cell anaplastic Ki-1 lymphoma at age 20 years, and 23 second- and higher degree relatives were affected. In two instances leukemia/lymphoma occurred in the context of Li-Fraumeni syndrome (LFS) and two other families showed striking clusters of unusual and early-onset malignancies. In several cases, children had genitourinary abnormalities of the type associated with the WT1 gene on chromosome 11p13. Some of these families may provide important subjects for study of WT genes in hematologic disease and lymphomas and for investigation of interaction between different tumor-suppressor genes, e.g., WT1 and other candidate WT genes, and p53.

Adolescent↗
PubMed1994

beta-Amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: implications to Alzheimer's disease.

We have previously reported (Hensley et al., Proc. Natl. Acad. Sci. USA (1994) in press) that beta-amyloid peptide fragments in aqueous media, in a metal-independent reaction, produce reactive peptide free radicals and reactive oxygen species. In contrast to the hours or days necessary to produce neurotoxicity and a detectable free radical for beta-amyloid, the extremely neurotoxic A beta(25-35) fragment of beta-amyloid peptide produces a detectable radical in minutes. We now report that A beta(25-35) is a potent lipoperoxidation initiator, as inferred from peptide-mediated reduction of nitroxyl stearate spin labels bound to rodent neocortical synaptosomal membranes. A beta(25-35) rapidly quenches the paramagnetism of membrane-bound 12-nitroxyl stearate spin probe deep within the lipid bilayer, but reacts poorly with the 5-nitroxyl isomer whose paramagnetic center is near the lipid/water interface. A beta(35-25), the non-neurotoxic reverse sequence of A beta(25-35), shows little proclivity to reduce either spin label. These findings are formulated into a "molecular shrapnel" model of neuronal membrane damage in Alzheimer's disease.

Alzheimer Disease↗
PubMed1994

Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation.

Identification of a biocompatible immunoprotective membrane to prevent graft rejection remained elusive until the development of microcapsules formulated in alginate high in guluronic acid. We report insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Encapsulated human islets were injected intraperitoneally in a diabetic patient with a functioning kidney graft. Insulin independence with tight glycaemic control was demonstrated 9 months after the procedure. These results warrant a trial of a high dose of encapsulated islets in early-onset diabetic patients.

Adult↗
PubMed1994

A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease.

beta-Amyloid is a 39- to 43-amino-acid neurotoxic peptide that aggregates to form the core of Alzheimer disease-associated senile (amyloid) plaques. No satisfactory hypothesis has yet been proposed to explain the mechanism of beta-amyloid aggregation and toxicity. We present mass spectrometric and electron paramagnetic resonance spin trapping evidence that beta-amyloid, in aqueous solution, fragments and generates free radical peptides. beta-Amyloid fragments, at concentrations that previously have been shown to be neurotoxic to cultured neurons, can inactivate oxidation-sensitive glutamine synthetase and creatine kinase enzymes. Also, salicylate hydroxylation assays indicate that reactive oxygen species are generated by the beta-amyloid-(25-35) fragment during cell-free incubation. These results are formulated into a free radical-based unifying hypothesis for neurotoxicity of beta-amyloid and are discussed with reference to membrane molecular alterations in Alzheimer disease.

Alzheimer Disease↗
PubMed1994

Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.

The entire coding sequence of the p53 gene was analysed for the presence of mutations in 12 families conforming to a restricted definition of Li-Fraumeni syndrome (classic LFS) and nine families with features of LFS conforming to a broader definition. Mutations were detected in seven families. Six were point mutations with one each affecting codons 175, 180, and 220 and three affecting codon 248. The seventh was a deletion/insertion mutation in exon 4. Germline mutations in p53 were a feature of families which included children with rhabdomyosarcoma and/or adrenal cortical carcinoma. Germline p53 mutations were detected in six of the nine families with such tumors. An analysis of these 7 mutations, together with 34 published examples, showed that more than one-half were transitions at CpG dinucleotides, suggesting that the majority of germline p53 mutations may arise as a result of spontaneous events. The most common cancers occurring in the 41 families with germline p53 mutations, in common with classic LFS, were bone and soft tissue sarcoma, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma, although less than one-half of the probands with germline p53 mutations came from classic LFS families. More than one-half of the cancers overall and nearly one-third of the breast cancers were diagnosed before 30 years of age. These observations have important implications for asymptomatic carriers of germline p53 mutations, and there is a need for international collaboration in the development of protocols for the management of such families.

Base Sequence↗
PubMed1994

Metastatic carcinoma of uncertain primary site: a retrospective review of 57 patients treated with vincristine, doxorubicin, cyclophosphamide (VAC) or VAC alternating with cisplatin and etoposide (VAC/PE).

BACKGROUND: Metastatic carcinoma of uncertain primary site (CUPS) is a common problem and has a poor prognosis. The intention of this study was to determine whether the addition of cisplatin and etoposide (PE) to vincristine, doxorubicin and cyclophosphamide (VAC) chemotherapy improves outcome. METHODS: Fifty-seven consecutive patients with an initial diagnosis of CUPS were studied. The first 40 patients had received six or 10 cycles of VAC and 17 patients VAC alternating with PE for six cycles. Review of histology using immunohistochemical techniques where appropriate was performed in all cases. RESULTS: Histologic review resulted in six tumors reclassified as non-Hodgkin's lymphoma (NHL), one as hepatocarcinoma, and one as adenocarcinoma. Six of the 11 responses occurred in patients with a review diagnosis of NHL. If the six cases of NHL and the case of hepatocarcinoma were excluded, there was no difference in survival between VAC and VAC/PE treated patients. Five patients with true CUPS who responded to VAC or VAC/PE had poorly differentiated histology, and this group (n = 24) also had a significantly longer survival. CONCLUSIONS: Some patients thought to have CUPS actually have NHL, and it is this group which responds well to chemotherapy. True CUPS patients respond to chemotherapy only if the tumor is poorly differentiated; survival is significantly longer for this group of patients. An advantage for VAC/PE over VAC chemotherapy was not identified.

Adenocarcinoma↗
PubMed1994

Modifications in service delivery and clinical treatment for women diagnosed with severe mental illness who are also the survivors of sexual abuse trauma.

Sexual abuse trauma and chronic revictimization are central to the experience of many women diagnosed with severe mental illness. The high reported prevalence rates of sexual abuse trauma among these women necessitate that program planners and clinicians be prepared to adapt their treatment interventions for use with trauma survivors. This article describes how current treatment approaches for women diagnosed with severe mental illness can be adapted to accommodate the special needs and vulnerabilities of sexual abuse trauma survivors. A history of trauma added to the clinical picture of longstanding and severe mental illness poses new diagnostic and treatment considerations, which are discussed. The full range of rehabilitation services--case management, residential placement and supervision, inpatient hospitalization, medication management, network intervention, and social skills training--must be grounded in an understanding of the trauma experience, informed by accurate assessment of the trauma, and accommodated to the woman's specific history of sexual abuse trauma.

Battered Women↗
PubMed1994

Genitourinary tumors in the families of children with renal tumors.

The occurrence of genitourinary tumors in the relatives of a population-based series of 218 children diagnosed with renal tumors was investigated. Family data on 92% (176 of 192) of Wilms' tumor (WT) patients and 77% (20 of 26) of other renal tumor patients were obtained. In all, 21 genitourinary tumors in first-degree relatives in 19 families were ascertained, together with 30 such tumors in second-degree relatives. Ten families were diagnosed with multiple genitourinary tumors, although none of these manifested familial WT. It is proposed that a small proportion of families of children with renal tumors has a genetic predisposition to develop genitourinary tumors and that these tumors may represent further manifestations of the pleiotropic effects of the WT1 gene or of other genes involved in WT predisposition.

Adult↗