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Biomedical subjects

T Lynch

Publications and source records attributed to T Lynch.

At least 91 records · Page 5Linked to original sources
PubMed1996

Evaluation of p53 protein expression in renal cell carcinoma: comparison of two antibodies.

The aims of this study were to establish a profile for the expression of p53 in primary renal cell carcinoma using the polyclonal antibody NCL-CB1 and the monoclonal antibody D07, and to compare the results of staining with both antibodies. Ninety-six cases were studied using formalin-fixed paraffin-embedded tissue. Positive nuclear staining ranged from 5% (D07) to 12% (NCL-CM1). Positive cytoplasmic staining ranged from 7% (D07) to 25% (NCL-CM1) of cases. Interobserver agreement was excellent. The findings suggest that such a low level of immunohistochemical positivity reduces any potential prognostic value for p53 in this tumour type.

Antibodies↗
PubMed1995

Generalized chorea in an infant with semilobar holoprosencephaly.

We report chorea in an infant with holoprosencephaly. Congenital structural brain disease has not been a reported cause of chorea. Cranial magnetic resonance imaging revealed small, fused frontal lobes with hypoplastic caudates. Our patient responded to symptomatic treatment with dopamine-depleting agents. It is likely that the mechanism for the chorea was a dysfunction of the striatum. The differential diagnosis of childhood chorea should include holoprosencephaly.

Child, Preschool↗
PubMed1995

Serotonin syndrome.

We describe a patient treated with trazodone, isocarboxazid, and methylphenidate hydrochloride who developed confusion, agitation, poor concentration, rigidity, myoclonus, involuntary movements, orthostatic hypotension, and hyperreflexia. CK was normal, and the syndrome resolved spontaneously over 12 hours. The serotonin syndrome occurs following the use of serotomimetic agents (serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, tryptophan, 3,4-methylenedioxy-methamphetamine, dextromethorphan, meperidine, S-adenosylmethionine) alone or in combination with monoamine oxidase inhibitors. It is characterized by various combinations of myoclonus, rigidity, hyperreflexia, shivering, confusion, agitation, restlessness, coma, autonomic instability, low-grade fever, nausea, diarrhea, diaphoresis, flushing, and rarely, rhabdomyolysis and death.

Depressive Disorder↗
PubMed1995

Familial progressive subcortical gliosis: presence of prions and linkage to chromosome 17.

Progressive subcortical gliosis (PSG) is a sporadic and familial dementing disease characterized pathologically by astrogliosis at the cortex-white matter junction, a feature present in some prion diseases. With immunocytochemical and Western blot analyses, we investigated the presence of deposits of the prion protein (PrP) and of the protease-resistant PrP isoform, the hallmarks of prion diseases, in six affected members of two large kindreds with PSG. The coding region of the PrP gene was sequenced and chromosomal linkage determined. We demonstrated "diffuse" PrP plaques in the cerebral cortex of two subjects from one kindred and protease-resistant PrP fragments in four of the five subjects examined. We found no mutation in the coding region of the PrP gene. Moreover, the disease was linked to chromosome 17 and not to chromosome 20, where the PrP gene resides. The familial form of PSG is the first human genetic disease characterized by the presence of protease-resistant PrP that lacks a mutation in the coding region of the PrP gene. The linkage to chromosome 17 suggests that other genes are involved in the PrP metabolism. Whether the protease-resistant PrP plays a primary or secondary role in the pathogenesis of this form of PSG remains to be determined.

Adult↗
PubMed1995

Aeromedical helicopter use following the 1989 Loma Prieta earthquake.

OBJECTIVE: To understand the role of aeromedical services in the 1989 Loma Prieta disaster response, a survey was conducted of aeromedical teams participating in the disaster. METHODOLOGY: An investigator interviewed flight team members from all six participating helicopter services. RESULTS: Aeromedical teams transported 31 patients after the earthquake. Of six helicopter teams, four reported landing zone (LZ) hazards. One flight team made determinations of death on five patients at one scene; two teams performed CPR enroute; two teams reported acting as airborne radio repeaters between communication centers, ground field units, and counties. Of six services, four performed over flight reconnaissance. CONCLUSION: Regional disaster managers should incorporate aeromedical services into disaster plans. This planning should include all of the roles played by aeromedical services; patient and equipment transportation, disaster reconnaissance, and communications linkage. Aeromedical services can play an essential role in disaster mitigation.

Air Ambulances↗
PubMed1994

Use of the immunotoxin N901-blocked ricin in patients with small-cell lung cancer.

In patients with small-cell lung cancer (SCLC), relapse with resistant disease often causes death. N901-blocked ricin (N901-bR), a murine monoclonal antibody (MAb)-blocked ricin immunotoxin, is a potential therapeutic for SCLC. N901-bR targets CD56, present on SCLC and cells of neuro-ectodermal origin. N901-bR kills up to 5 logs of CD56-positive cells at a concentration of 0.25 nM, while CD56-negative cells require 1000-fold more drug to achieve similar cell kill. We treated 21 patients with relapsed or refractory SCLC with a single 7-day course of N901-bR as a continuous infusion. We determined the MTD and toxicity profile, demonstrated drug binding to tumor cells in biopsies of lung, liver and bone marrow, and determined the time to development of human anti-mouse and anti-ricin antibodies. One patient had a documented PR and 6 patients demonstrated stable disease. Toxicity included transient elevation of liver enzymes, mild thrombocytopenia, hypoalbuminemia, fever, malaise, and evidence of capillary leak syndrome. Toxicities were controllable and reversible. No apparent drug-related central- or peripheral-nervous-system toxicity was noted by serial neurologic examinations, EMGs, and nerve conduction studies. Trials of N901-bR are planned in SCLC patients achieving CR and PR following chemoradiotherapy, and in relapsed/refractory patients. Anti-B4-bR will be added as an immunosuppressant in order to permit delivery of multiple courses of N901-bR. Additional trials will investigate synergy with conventional chemotherapeutics and the use of N901-bR as a sensitizing agent for chemotherapy-resistant tumors.

Animals↗
PubMed1994

Effect of recombinant human interleukin-3 on haematological recovery from chemotherapy-induced myelosuppression.

Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m2, days 1-3; carboplatin 300 mg/m2, day 1; etoposide 75 mg/m2, days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 micrograms/kg/d. At 15.0 micrograms/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 micrograms/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 micrograms/kg/d, IL-3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 micrograms/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted.

Adolescent↗
PubMed1994

Clinical characteristics of a family with chromosome 17-linked disinhibition-dementia-parkinsonism-amyotrophy complex.

We studied the clinical features, pathology, and molecular genetics of a family (Mo) with an autosomal dominant disinhibition, frontal lobe dementia, parkinsonism, and amyotrophy. We examined seven affected members and gathered clinical information on another six. The mean onset was at age 45 years. Personality and behavioral changes (disinhibition, withdrawal, alcoholism, hyperphagia) were the first symptoms in twelve. There was early memory loss, anomia, and poor construction with preservation until late of orientation, speech, and calculations. All affected members examined had rigidity, bradykinesia, and postural instability. Mean duration to death was 13 years. We studied the neuropathology of six individuals, five of whom had been examined in life. There was atrophy and spongiform change in the frontotemporal cortex, and neuronal loss and gliosis in the substantia nigra and amygdala. Two individuals, including one with fasciculations and muscle wasting, had anterior horn cell loss. There were no Lewy bodies, neurofibrillary tangles, or amyloid plaques. We call this disorder the "disinhibition-dementia-parkinsonism-amyotrophy complex" (DDPAC), based on the clinical syndrome found in this family and linkage to chromosome 17.

Adult↗
PubMed1994

Reorganizing an academic medical center in a period of change.

On June 14, 1993, the University of Alberta Hospital was reorganized with the intention of making it more client focused. The decision to transform the organizational structure of the hospital was not taken lightly. The redesign decision was influenced by a host of factors in the external environment and the impact of changes within the organization from the implementation of a total quality management (TQM) philosophy.

Academic Medical Centers↗
PubMed1994

Localization of disinhibition-dementia-parkinsonism-amyotrophy complex to 17q21-22.

Disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) is defined by familial adult-onset behavioral disturbance, followed by frontal lobe dementia, parkinsonism, and amyotrophy in variable proportions. A genetic etiology of DDPAC was suspected because of the familial clustering in family Mo, despite their wide geographic distribution. We have mapped the DDPAC locus to a 12-cM (sex averaged) region between D17S800 and D17S787 on chromosome 17q21-22. The basis for the variability of the clinical findings and pathology in DDPAC is unknown but suggests that the DDPAC locus should be screened as a candidate locus in family studies of conditions with behavioral abnormalities and neurological degeneration.

Chromosome Mapping↗
PubMed1993

Long-term traumatic stress reactions in British Falklands War veterans.

This brief report summarizes the first available findings on long-term traumatic stress syndromes among ex-servicemen who are veterans of the Falklands War. The results reveal a correlation between physical injury during the War and post-traumatic stress disorder, indicating the need for a long-term follow-up survey incorporating treatment evaluations and welfare rights.

Adult↗