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Biomedical subjects

M Harper

Publications and source records attributed to M Harper.

At least 37 records · Page 2Linked to original sources
PubMed2000

Irinotecan in the management of patients with pancreatic cancer.

Synergy with no overlapping toxicities has been demonstrated for the combination of irinotecan (Camptosar, CPT-11) and gemcitabine (Gemzar) in vitro. Results of a single-institution phase I study in which patients with previously untreated pancreatic cancer were given irinotecan and gemcitabine were promising, with two of three patients achieving a partial response. Because of the favorable outcome of the phase I study, a multicenter phase II trial was undertaken in previously untreated patients with pancreatic carcinoma. Data from other sites entering patients in this phase II study have been analyzed, and a multicenter phase III trial of single-agent gemcitabine vs the irinotecan combination in first-line treatment of patients with locally advanced or metastatic pancreatic cancer is underway.

Antineoplastic Agents, Phytogenic↗
PubMed1999

A prospective randomized trial evaluating tissue effects of finasteride therapy in benign prostatic hyperplasia.

Finasteride is widely used for the treatment of benign prostatic hyperplasia (BPH). Its therapeutic efficacy is believed to be mediated through selective inhibition of prostatic 5alpha-reductase (type II). This prospective, controlled, randomized study examines various relationships between changes in tissue 5alpha-reductase isozyme activity, epithelial proliferative index and morphology in men with BPH treated with finasteride for 6 months, and correlates these with clinical response. Thirty-one patients presenting with symptomatic bladder outflow obstruction were prospectively randomized to receive either finasteride or placebo (2:1) for 24 weeks. Of these, 27 men aged 55-80 y (median 69 y) completed the study, including 18 patients on treatment. Symptom score determination, uroflow and prostate volume were assessed at baseline and end of study. Prostatic tissue was obtained by ultrasound-guided needle biopsy at baseline and by transurethral resection (TURP) at end of study for biochemical and morphometric analysis. Epithelial proliferation was examined quantitatively in the resected tissue using MIB-1 antibody to Ki-67 and counting the percentage of positively staining cells. Type II 5alpha-reductase activity was strongly inhibited by finasteride in resected BPH tissue, with over 100-fold decrease in V(max) (P=0.001), whereas the type I isozyme was inhibited 5-fold (P=0.005). Selective inhibition of type II 5alpha-reductase was demonstrated in all treated patients. No significant difference in epithelial proliferation was observed between the finasteride and placebo groups. Epithelial proliferation was, however, greater in prostatic tissue with histological manifestation of inflammation (2.02% vs 0.89%, P=0.001). Positive correlation between the total epithelial volume and the ratio of transition zone volume/total prostate volume was observed in the placebo group (r=0.834), whereas there was no such correlation in men taking finasteride (r=-0.300), consistent with a reduction in epithelial content in the treatment group. Improvement in uroflow and reduction in prostatic volume in patients treated with finasteride did not reach statistical significance. This study shows that finasteride causes inhibition of 5alpha-reductase activity in human BPH tissue with selectivity for the type II isozyme. In spite of this, no significant effects in epithelial proliferation or tissue morphology were demonstrated. The presence of inflammation was, however, associated with significantly greater proliferative activity. The power of this study was limited by the small number of recruited patients, and a larger study would be required for further investigation of morphological changes induced by finasteride in BPH tissue and their biochemical basis.

Journal Article↗
PubMed1999

Management of penetrating injury to the petrous internal carotid artery: case report.

We report the management of a penetrating foreign body injury to the neck with a length of fencing wire traversing the internal carotid artery within the petrous temporal bone and entering the middle cranial fossa. Discussion points include methods of haemorrhage control, as well as ligation versus repair or bypass as the definitive treatment.

Adolescent↗
PubMed1999

Non-typhi Salmonella bacteremia in children.

BACKGROUND: Non-typhi Salmonella (NTS) infections are a frequent cause of self-limited diarrheal illness in healthy children. Bacteremia is a known complication of NTS infection, but the management of children with bacteremia has been based on limited data. OBJECTIVE: To study the outcomes of pediatric patients with NTS bacteremia. METHODS: Retrospective review of patients with NTS bacteremia covering a 16-year period at an urban pediatric hospital. Clinical data from the initial visits and any follow-up visits or hospitalizations were abstracted from the medical record. RESULTS: We studied 144 patients. Median age was 10.5 months. Fifty-four patients were hospitalized at the initial visit including all the patients with immunodeficiency (n = 12). Of the 90 patients initially managed as outpatients, 79 were subsequently admitted; only 1 of these patients developed a focal complication. Persistent bacteremia was found in 51 (41%) patients. Among nonimmunocompromised patients, persistent bacteremia was noted in 34% [95% confidence interval (CI), 20 to 52%] of those initially treated with oral antibiotics, 52% (CI 30 to 74%) of those initially treated with a parenteral dose of antibiotics and in 31% (CI 22 to 43%) of those who were not initially given antibiotics. No laboratory or clinical factors predicted persistent bacteremia. Twelve patients developed focal infections: 3 of 119 previously healthy children (2.5%, CI 0.5 to 7%); and 9 of 25 children with underlying medical conditions (36%, CI 19 to 57%). Focal infections included meningitis (3), osteomyelitis (4), septic arthritis (2), pneumonia (2) and cholangitis (1). CONCLUSIONS: NTS bacteremia occurs in otherwise healthy children, although the risk of focal infections is small. Patients with NTS bacteremia frequently have persistent bacteremia at follow-up regardless of initial antibiotic treatment.

Bacteremia↗
PubMed1998

Expression of the mitotic motor protein Eg5 in postmitotic neurons: implications for neuronal development.

It is well established that the microtubules of the mitotic spindle are organized by a variety of motor proteins, and it appears that the same motors or closely related variants organize microtubules in the postmitotic neuron. Specifically, cytoplasmic dynein and the kinesin-related motor known as CHO1/MKLP1 are used within the mitotic spindle, and recent studies suggest that they are also essential for the establishment of the axonal and dendritic microtubule arrays of the neuron. Other motors are required to tightly regulate microtubule behaviors in the mitotic spindle, and it is attractive to speculate that these motors might also help to regulate microtubule behaviors in the neuron. Here we show that a homolog of the mitotic kinesin-related motor known as Eg5 continues to be expressed in rodent neurons well after their terminal mitotic division. In neurons, Eg5 is directly associated with the microtubule array and is enriched within the distal regions of developing processes. This distal enrichment is transient, and typically lost after a process has been clearly defined as an axon or a dendrite. Strong expression can resume later in development, and if so, the protein concentrates within newly forming sprouts at the distal tips of dendrites. We suggest that Eg5 generates forces that help to regulate microtubule behaviors within the distal tips of developing axons and dendrites.

Animals↗
PubMed1998

Acceptability to patients of a home hospital.

OBJECTIVE: To examine the acceptability to older patients of receiving care in the home for acute medical conditions that require hospital level care by current standards. DESIGN: Interviews with patients during hospitalization regarding their views of a hypothetical "home hospital." PARTICIPANTS: Patients (n = 87) admitted to a community-based academic medical center with a primary diagnosis of pneumonia, congestive heart failure, or chronic obstructive airway disease, their nurses (n = 111), and resident physicians (67). MEASUREMENTS: A questionnaire was developed to measure several domains of acceptability and expectations for care. RESULTS: A majority of patients agreed that treatment in a home hospital would be more comfortable compared with treatment in a hospital (78.5%), would be less likely to result in an infection (62.5%), and would not be a burden to their family (71.8%). There was less certainty that medical care at home can be as good as in the hospital (56.9%). Nearly three-quarters (72.3%) of patients would choose home hospital if it were available. CONCLUSION: Patients may be ready to accept home hospital as an alternative for acute care. The acceptability of home hospital to acutely ill older patients is a critical factor in the development of this alternative for care and has the potential for improving satisfaction with care, reducing complications, hastening return to function, and, possibly, of lowering costs of care.

Acute Disease↗
PubMed1998

Long-term reduction in asthma morbidity following an asthma self-management programme.

The adult "credit card" asthma self-management plan has been shown to be an effective and acceptable system for reducing asthma morbidity when introduced as part of a 6 month community-based asthma programme. The aim of the present study was to assess the effectiveness of the credit card plan 2 yrs after the end of the programme. Markers of asthma morbidity and use of medical services were compared during the 12 months before enrolment, and 2 yrs after completing the 6 month asthma programme. Of the 69 participants who originally enroled in the 6 month asthma programme, 58 were surveyed 2 yrs after completion of the programme. These participants showed a significant improvement in all but one of the asthma morbidity measures. The proportion waking most nights with asthma in the previous 12 months decreased from 29 to 9% (p=0.02), emergency visits to a general practitioner decreased from 43 to 16% (p=0.001), hospital emergency department visits with asthma decreased from 19 to 5% (p=0.02) and hospital admissions decreased from 17 to 5% (p=0.04). Only 24% of patients reported that they usually monitored their peak flow rate daily, but this increased to 73% during a "bad" attack of asthma. A long-term reduction in asthma morbidity and requirement for acute medical services can result following the introduction of the adult credit card asthma self-management plan. Adult patients with asthma are most likely to undertake peak flow monitoring preferentially during periods of unstable asthma, rather than routinely during periods of good control.

Adult↗
PubMed1997

Maternal deaths due to homicide and other injuries in North Carolina: 1992-1994.

OBJECTIVE: To determine the role of homicide and other injuries in maternal deaths in North Carolina over the three-year period from 1992 through 1994. METHODS: Maternal deaths were identified from death certificates that indicated a maternal death and through an enhanced surveillance system that matches death certificates with live-birth and fetal-death certificates. Deaths were classified as direct, indirect, medically unrelated, or injury-related. Patterns of prenatal care were ascertained from the matching live-birth or fetal-death certificates. Maternal death rates for whites and nonwhites were calculated. RESULTS: The most common cause of maternal death was injury, accounting for 62 of the 167 deaths (37%). Homicide was the most common cause of injury-related death (35.5%). The relative risk of maternal death for nonwhites compared with whites was 1.8 (95% confidence interval [CI] 1.6, 2.1). Similarly, their relative risk for injury-related maternal death was 1.7 (95% CI 1.4, 2.2). CONCLUSION: It is essential to include an analysis of injury-related deaths in maternal mortality reporting. As the most common cause of maternal deaths, injury is not limited to densely populated, metropolitan areas. Counseling regarding injury prevention, domestic violence, and depression should be a part of both prenatal and postpartum care.

Adult↗
PubMed1997

Prospective evaluation of clinical criteria to select older persons with acute medical illness for care in a hypothetical home hospital.

OBJECTIVE: To evaluate criteria to select older persons who need hospitalization for common acute medical illnesses for care in a hypothetical home hospital. DESIGN: Prospective record review. SETTING AND PARTICIPANTS: Patients aged 65 and older admitted to the general medical service of a community-based university hospital. MEASUREMENTS: We developed illness-specific selection criteria to identify older persons with certain acute medical conditions for treatment in a hypothetical home hospital. The selection criteria were reviewed prospectively against all community-dwelling older patients admitted to the general medical service of a community-based university hospital over a 2-month period. We determined eligibility for home hospital admission based on information available at the time of admission and then tracked the patient's hospital course. RESULTS: One hundred fifty-seven admissions of 143 patients were reviewed. The selection criteria identified 33% of patients admitted to the acute hospital with one of the three target diagnoses as eligible for a home hospital model of care had it been available. Eligible patients experienced shorter lengths of stay (3.7 vs 5.4 days, P = .012), fewer mean number of procedures performed (0.98 vs 1.70, P = .001), fewer mean number of complications (0.17 vs 0.56, P = .010), and fewer events that could be handled only in the acute hospital setting (P = .036). In addition, in logistic regression analysis, three criteria for home hospital ineligibility, pulmonary congestion associated with ischemic chest pain (odds ratio 6.85, 95% CI 2.64, 17.81), the presence of an acute coexisting illness requiring hospitalization independent of the target conditions (odds ratio 2.66, 95% CI 1.11, 6.41), and significant pulmonary congestion after initial treatment (odds ratio 14.4, 95% CI 1.77, 117.41) were significantly associated with items difficult to accomplish at home. CONCLUSIONS: Criteria can be delineated that identify older persons with acute medical illnesses who may be suitable for treatment in a home hospital.

Acute Disease↗
PubMed1996

An apparent autocrine mechanism amplifies the dexamethasone- and retinoic acid-induced expression of mouse lipocalin-encoding gene 24p3.

We have isolated, sequenced and characterized the mouse 24p3 gene. The 24p3 protein is a member of the lipocalin family comprising secreted transporters of hydrophobic ligands. The 24p3 cDNA had been initially isolated during a search for genes overexpressed during a SV40-induced mitotic reaction [Hraba-Renevey et al., Oncogene 4 (1989) 601-608]. 24p3 comprises six exons, five introns and 793 bp of 5' regulatory region. The transcription start point (tsp) was identified by primer extension. Putative regulatory elements, including a TATA-like box and two glucocorticoid responsive core elements (GRE), have been mapped in the 5'-flanking region. Based on this observation, we examined the effect of a glucocorticoid (dexamethasone, Dex) on 24p3 expression. Dex induced the expression of 24p3 dramatically in the absence of de novo protein synthesis. This activation was further amplified by an apparent autocrine mechanism. Similar results were obtained with retinoic acid. Using the cat reporter gene system, we have shown that the 5'-flanking region of 24p3 confers Dex inducibility. Furthermore, we have identified a 43-bp region of the 24p3 promoter required for the Dex responsiveness. The biological implications are discussed in light of these results.

Acute-Phase Proteins↗
PubMed1996

Experience in the use of the NIOSH diffusive sampler evaluation protocol.

Diffusive sampler operation may be affected by a large number of factors. Interactions between the factors may also be important. A protocol for determining sampler performance has been developed by the National Institute for Occupational Safety and Health (NIOSH) that addresses sampler precision and accuracy when these factors vary within the ranges normally encountered in the field. However, it is costly, time-consuming, and often unnecessary to apply all of the tests to each sampler for every possible chemical hazard. A sampler shown to sample a specific vapor accurately may be assumed to require fewer tests to assure equal performance with related chemicals. The criteria used to define the reduced tests depends somewhat on sampler design, and the justification for applying the criteria must depend on information gained from validating a large selection of related chemicals using the full protocol. Thus, the full protocol remains the standard of reference for the lower validation level. Based on these considerations a "bilevel validation" approach was developed for the SKC 575 series diffusive sampler. Application of the bilevel approach to the NIOSH protocol is described, and the results are related to the full NIOSH protocol and also to a European validation protocol. The European protocol recognizes the validity of reduced tests for homologue validation. The conclusions are that (1) it is feasible to validate a sampler for a large number of organic vapors using the NIOSH protocol and that this number can be substantially increased by use of a bilevel approach, saving time and resources, and (2) samplers validated to either the NIOSH or European protocol should be accepted as meeting the requirements of the other.

Air Pollutants, Occupational↗
PubMed1996

Invasive pneumococcal infections in human immunodeficiency virus-infected children.

Invasive pneumococcal infection (IPI) is the most common serious bacterial infection in human immunodeficiency virus (HIV)-infected children. Data from a population-based pediatric HIV surveillance project were used to determine the incidence of IPI in HIV-infected children and to conduct a case-control study assessing potential risk factors for IPI in HIV-infected children. There were 50 episodes of IPI and a cumulative incidence of 6.1 cases/100 patient-years through age 7 years. Children with IPI were more likely to have a prior AIDS diagnosis (odds ratio, 4.2; 95% confidence interval, 1.2-15.1) and higher levels of IgG and IgM (P=.01) than were controls. In a separate case-control study, the manifestations of IPI in HIV-infected children were compared with those in HIV-negative controls. Focal complication rates in the 2 groups did not differ; however, HIV-infected children were less likely than controls to have leukocytosis (P<.001) and more likely to have isolates with penicillin resistance (P=.03).

Age Factors↗
PubMed1996

Ethical decision-making near the end of life.

For ethical decision-making near the end of life, autonomy is the moral North Star. At the same time, for some treatments, the burdens so clearly outweigh benefits that physicians may make a judgment not to offer the treatment. This is often clearer in surgery. A person with colon cancer and metastases may not insist on resection of the metastases. For some reason, some treatments have escaped these logical constraints. Attempted resuscitation of a dying patient is a good example. The circumstances in which a physician may make choices on behalf of a competent, terminally-ill patient without consent, and even without notification, are hotly debated, but data suggest that physicians do so frequently. Patients who lack capacity present even more difficult challenges. Advance directives, when available, can be extremely helpful, but even with them difficult problems can remain. If advance directives have not been established, family and close friends are an obvious source of guidance. Their legal role varies in different jurisdictions; in practice, they are crucial in bedside decision-making. Guardianship and alternatives to it remain a poor last resort. Euthanasia is a very difficult problem. We believe it is semantically misleading to lump under the term "passive euthanasia" those circumstances where potentially life-sustaining treatment is withheld or withdrawn. The tension between patient autonomy and medical common sense remains unresolved within the "futility" controversy. The authors believe it serves no purpose to discuss carefully with dying patients propositions that are nonsense. At the same time, physicians must not confuse decisions about quality of life with judgements about treatment effectiveness. We believe that what many, although not all, dying patients want are physicians with intelligent compassion who can take care of them through the dying process.

Advance Directives↗
PubMed1995

Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo.

We have isolated a human homolog of Xenopus Eg5, a kinesin-related motor protein implicated in the assembly and dynamics of the mitotic spindle. We report that microinjection of antibodies against human Eg5 (HsEg5) blocks centrosome migration and causes HeLa cells to arrest in mitosis with monoastral microtubule arrays. Furthermore, an evolutionarily conserved cdc2 phosphorylation site (Thr-927) in HsEg5 is phosphorylated specifically during mitosis in HeLa cells and by p34cdc2/cyclin B in vitro. Mutation of Thr-927 to nonphosphorylatable residues prevents HsEg5 from binding to centrosomes, indicating that phosphorylation controls the association of this motor with the spindle apparatus. These results indicate that HsEg5 is required for establishing a bipolar spindle and that p34cdc2 protein kinase directly regulates its localization.

Amino Acid Sequence↗