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Biomedical subjects

R Rudd

Publications and source records attributed to R Rudd.

33 records · Page 2Linked to original sources

Epithelial differentiation in the absence of extracellular matrix.

To investigate the regulation of epithelial differentiation, normal human epidermal keratinocytes were cultured floating on the surface of culture medium without attachment to a solid substrate. Keratinocytes spread out on the surface of the medium, proliferated and differentiated either into several flat lacy sheets 1 to 3 cells thick (on medium containing 0.15 mM calcium) or formed one single aggregate of cells from 5 to 15 cells in thickness on medium containing 1.15 mM calcium. The cell aggregates demonstrated a pattern of ordered epithelial differentiation. Levels of progressive differentiation resembling the structure of normal human epidermis were identified by light microscopy, immunohistochemistry, and electron microscopy. Differentiation proceeded from cells at the air side toward cells at the medium side with basal appearing cells on the air side and keratinocytes expressing filaggrin and involucrin on the side toward the medium. These results demonstrate that organized epithelial differentiation can occur in the absence of extracellular matrix. In contrast with other air-liquid interface cultures, epithelial differentiation in the absence of extracellular matrix progresses from air towards medium.

Cell Adhesion↗

Intensive weekly chemotherapy for good-prognosis patients with small-cell lung cancer.

A weekly, intensive chemotherapy regimen has been used to treat 70 patients with small-cell lung cancer (SCLC). Forty-five patients had limited disease (LD) and 25 extensive disease (ED) with good prognostic features. The regimen consisted of cisplatin 50 mg/m2 intravenously (IV) day 1 and etoposide 75 mg/m2 IV days 1 and 2, alternating weekly with ifosfamide 2 g/m2 IV day 8 and doxorubicin 25 mg/m2 IV day 8, for a total of 12 weeks. Dose modifications were made according to defined hematologic criteria. Responding patients with limited disease subsequently received mediastinal radiotherapy. Overall response to chemotherapy was 91% with a complete response (CR) rate of 50%. Forty-five patients with limited disease (LD) achieved an overall response rate of 91% with a CR rate of 51%, and 25 patients with extensive disease (ED) achieved an overall response rate of 92% with a CR rate of 48%. Median survival for the whole group was 54 weeks (LD, 58 weeks; ED, 42 weeks). Hematologic toxicity was predictable, without the wide fluctuations in WBC count seen in conventional 3-weekly regimens. In all, one quarter of treatment courses were delayed, most frequently because of leukopenia. Dose reductions were required in 63% of cases. The average delivered dose intensity was calculated and shown to be 73% of projected. Nonhematologic toxicity was mild with nausea and vomiting being the most common. This weekly schedule of chemotherapy has proved to be active and well tolerated and is currently being compared with conventional 3-weekly chemotherapy in a randomized study.

Adult↗

Mitomycin, ifosfamide and cisplatin in non-small-cell lung cancer.

Chemotherapy with mitomycin C, ifosfamide and cisplatin (MIC) is reported to produce responses of 56% and 69% in inoperable non-small-cell lung cancer (NSCLC). We evaluated the regimen in 45 similar patients who received up to six courses of 6 mg/m2 mitomycin C, 3 g/m2 ifosfamide, and 50 mg/m2 cisplatin every 3 weeks. In all, 18 patients had limited disease (LD) and 27 had extensive disease (ED). A total of 18 patients responded (40%), 9/18 with LD and 9/27 with ED; there were 4 complete responders. The median duration of response was 25 weeks, and median survival was 32 weeks (range, 2-96 weeks). Toxicity was moderate. Nausea and vomiting were controlled with i.v. dexamethasone and high-dose metoclopramide. Other toxicities included myelosuppression and alopecia. This study confirms that MIC is one of the most active regimens for treatment of NSCLC, with acceptable toxicity.

Adult↗

Systemic autoimmune disease and concurrent nematode infection in a dog.

Systemic lupus erythematosus was diagnosed in a dog with concurrent nematode infection. The clinical signs of disease were unusually severe and included multiple neurologic deficits, polyarthritis, and weight loss. The dog was thrombocytopenic, and serotest results included positive lupus erythematosus test, positive rheumatoid factor test, positive antinuclear antibody test, hypergammaglobulinemia, and high platelet-associated IgG concentration. After treatment of hookworm, whipworm, and heartworm infections concurrently with corticosteroid and empiric treatment, the dog's condition improved. However, 10 days later, cyclophosphamide administration was necessary for continued immunosuppression. The dog was euthanatized because of progressive deterioration and development of canine coronavirus diarrhea. Serotest data generated from the dog's serum obtained at the time of referral suggested that autoantibodies and circulating immune complexes may have included IgE isotypes.

Ancylostomiasis↗

Regional lung microvascular permeability using dual isotope scintigraphy.

We have extended the dual isotope probe technique of Basran et al. for the measurement of pulmonary microvascular permeability (PMVP) to include gamma camera data acquisition and functional imaging of the plasma protein accumulation index (PPA) throughout the lung fields. The study group consisted of 11 patients with possible increased PMVP following the drainage of a pleural effusion or the evacuation of air from a pneumothorax, and 11 control patients. The PPA was calculated (1) for probe data, (2) on a pixel by pixel basis for the camera data, the results being stored in a functional image and (3) for four pixel x four pixel regions of interest positioned over the lung fields using the functional image and raw data as a guide. Functional images of the control group showed uniformly low PPAs throughout the lung fields. Nine of the eleven patients in the effusion/pneumothorax group showed discrete areas of increased PPA on the functional images. In the effusion/pneumothorax group, the re-expanded lung four pixel x four pixel ROI PPA values were significantly higher than the nonexpanded lung ROI values (p less than 0.001). The re-expanded lung ROI values were also significantly higher than the mean of the left and right lung ROIs in the control group (p less than 0.01). Five of the eleven patients in the effusion/pneumothorax group had probe PPAs that differed significantly from zero. We believe that probe positioning problems in the absence of sufficient clinical guidelines were largely responsible for there being no overall significant difference in the probe PPAs between the two study groups.

Adult↗

Humoral response to defined epitopes of tubercle bacilli in adult pulmonary and child tuberculosis.

In order to investigate the humoral response to tuberculosis in different categories of patients, serum antibody levels to six epitopes of Mycobacterium tuberculosis in adult pulmonary and child tuberculosis were determined. Serum antibody titres were determined by competitive inhibition with radio-labelled murine monoclonal antibodies in 67 adults and 85 children with tuberculosis and in 79 age-matched controls. BCG vaccination (n = 39) and self-healed tuberculosis (n = 11) in adults gave rise to higher antibody titres to TB68, TB23 and TB72 epitopes (all p less than 0.003) when compared to non-vaccinated controls (n = 18). TB68 titres were higher (p = 0.006) in self-healed than in vaccinated adults. Adult sputum-negative patients (n = 15) had higher titres to TB71 (p = 0.015) and ML34 (p = 0.02) epitopes compared to BCG-vaccinated healthy controls, while sputum-positive patients (n = 41) had higher titres to all epitopes tested (all p less than 10(-4]. The diagnostic sensitivity, with a 95% specificity, was best with the combination of probes TB23, TB68, TB72 for sputum-positive (85%) and TB78, ML34 (53%) for sputum-negative patients. Antibody titres in children with tuberculosis were lower than in adult patients; diagnostic sensitivity in histologically or microbiologically proven cases (n = 18) was only 44%, while that in mediastinal lymph-adenitis (n = 67) was 13.5%. This study suggests that the magnitude and specificity of the humoral response to tubercle bacilli varies with site and severity of infection; the implications for pathogenesis or protective immunity are discussed.

Adolescent↗

A teaching hospital medical clinic: secondary rather than primary care.

Although medical clinics in teaching hospitals are said to dispense primary care, the assertion has not been established by formal descriptions of care in such clinics. In this paper the authors describe 287 patient visits to a medical polyclinic (where generalists and subspecialists of internal medicine practice together) over a one-year period. The prevalence of disease was much higher than in existing descriptions of office-based primary care. The majority of visits to subspecialists involved medical problems relevant to the subspecialty, but both subspecialists and generalists dealt with medical problems across subspecialty lines because most patients had multiple problems. Although the data indicate these patients' need for accessibility, comprehensiveness, coordination, and continuity is at least as great as that of patients receiving primary care, this clinic is most appropriately described as a secondary-care facility.

Aged↗

A qualitative evaluation of the Harvard Cancer Risk Index.

There is an extensive amount of information in the popular press about cancer risk factors. The volume and sometimes contradictory nature of this information makes it difficult for individuals to understand their own level of risk or how one risk factor compares with another. The Harvard Cancer Risk Index (HCRI) was developed by an interdisciplinary working group of epidemiologists and behavioral scientists to educate the public about the major risk factors associated with the 11 most common forms of cancer in the United States. Following the development and validation of the HCRI, we initiated a qualitative research study to obtain initial feedback on the wording and presentation of the index and to elicit information regarding the meaning of risks, perception of cancer, and interpretation of the HCRI results. The results indicated that the HCRI was well received by participants and that they highly regarded the inclusion of information related to the latest risks for cancer and the description of the mechanisms by which these factors impact on risk. Personalization of the risk score helped participants to focus on behaviors that they could change. However, dissatisfaction with the HCRI was noted by some participants because exposures they believed to be important were not included (e.g., poverty, toxic waste, air pollution). Evaluation of the impact of the index on intention to change provided preliminary evidence that this may be an effective toll for helping mobilize individuals toward change across a number of risk factors. Further quantitative evaluation of the HCRI is planned.

Adult↗