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Biomedical subjects

M A Scott

Publications and source records attributed to M A Scott.

At least 73 records · Page 4Linked to original sources

The histologic spectrum of hepatic cat scratch disease. A series of six cases with confirmed Bartonella henselae infection.

Cat scratch disease (CSD), a common cause of regional lymphadenitis, has been linked to Bartonella henselae infection. Although rare, dissemination with hepatic involvement has been documented. Six cases of hepatic CSD were retrieved and probed for B. henselae DNA. Hematoxylin-eosin, trichrome, methenamine silver, Gram, Ziehl-Neelsen, and Warthin-Starry stained slides were reviewed by all authors, and the histologic findings were recorded. B. henselae infection was confirmed in all cases using combined polymerase chain reaction and Southern blot methods. All biopsies contained multiple granulomas, many with characteristic stellate abscesses surrounded by three distinct zones: an inner layer of palisading histiocytes, an intermediate lymphocytic rim, and an outermost zone of fibrosis. One case had noncaseating granulomas with prominent giant cells. Warthin-Starry stains were positive in two. The surrounding parenchyma in all cases contained lymphocytic infiltrates within expanded fibrotic portal triads and adjacent dilated sinusoids. There is a distinct spectrum of histologic changes in hepatic CSD. Although the unit lesion is granulomatous, the organization varies markedly. All cases show predictable nonspecific surrounding parenchymal changes. When multiple hepatic lesions are found in patients with constitutional symptoms suggesting an infectious illness, CSD should be included in the differential diagnosis.

Adult↗

Value of videostroboscopic parameters in differentiating true vocal fold cysts from polyps.

Differentiating between benign true vocal fold (TVF) cysts, polyps, and nodules on the basis of their gross appearance would be advantageous in determining the need for surgical therapy. A retrospective study of 32 patients covering 31 months was done to assess the ability to differentiate these lesions on the basis of stroboscopic parameters. Stroboscopic examinations were evaluated for symmetry, amplitude, periodicity, mucosal wave, and closure. Preoperative diagnoses were validated with operative and histologic confirmation. Mucosal wave was absent or diminished in 100% of TVF cysts and present or increased in 80% of TVF polyps (P < .05). Thirty-one percent of original histopathologic diagnoses were modified after pertinent clinical information was provided to the pathologist. Therefore, stroboscopic evaluation of mucosal wave is helpful in preoperative differentiation of TVF cysts and polyps, and providing clinical information to the pathologist is critical for useful histologic information.

Adult↗

Immunohistochemical characterization of benign laryngeal lesions.

It has been proposed that laryngeal nodules and polyps represent injury to the basement membrane zone of the vocal fold. Repeated trauma from shearing forces produced by excessive or abusive phonation leads to basement membrane zone disruption and thickening. This thickening, along with poorly understood vascular changes, creates the characteristic clinical appearance of the vocal nodule or polyp. As such, to better understand vocal fold nodules it is imperative to characterize the extracellular matrix in this area of injury. Secondary to the small size and relatively acellular nature of these lesions, hematoxylin and eosin (H & E) preparations of histologic material are unsatisfying. A previous study examined this area with immunohistochemical techniques to better characterize its contents. The report, however, contained little information with regard to the clinical appearance of the lesions prior to excision. Therefore, we were prompted to review histologic material from 31 patients who underwent microsurgical excision of 41 benign lesions, vocal nodules (4), polyps (19), polypoid corditis (4), and cysts (14) with immunohistochemical techniques to characterize the patterns of fibronectin and collagen type IV within these lesions. Normal human vocal folds were stained for control. All material was correlated with the H & E preparations and the clinical diagnosis. Collagen type IV and fibronectin appeared present in relatively abnormal patterns in the areas adjacent to the lesion. This study validates earlier results. In addition, correlation with clinical data allows association of immunohistochemical staining patterns with clinical diagnosis.

Adolescent↗

Peripheral blood progenitor cell transplantation: a single centre experience comparing two mobilisation regimens in 67 patients.

Between June 1991 and January 1995 we performed 67 peripheral blood progenitor cell transplants (PBPCT). Ten patients (group 1) were mobilised with 7 gm/m2 of cyclophosphamide followed by daily G-CSF injections (5 micrograms/kg, subcutaneously). When the white cell count reached 1 x 10(9)/1 they were leukapheresed for 5 days. After stem cell infusion they received G-CSF (10 micrograms/kg/day) until the neutrophil count reached 1.5 x 10(9)/1. Fifty-six patients had PBPCs mobilised with 3 gm/m2 of cyclophosphamide followed by daily subcutaneous G-CSF (5 micrograms/kg) and PBPCs were harvested on 2 consecutive days, when the white cell count rose to 4 x 10(9)/1. After stem cell infusion this group did not receive G-CSF. In 47 of the 56 patients (group 2) adequate MNC (> or = 4 x 10(8)/kg) and/or CFU-GM (> or = 10 x 10(4)/kg) were obtained. Insufficient MNC and/or CFU-GM were obtained in 10 patients. They were therefore transplanted using a combination of bone marrow and peripheral blood progenitor cells (group 3). Overall 64 patients successfully engrafted. Median days to neutrophils > or = 0.5 x 10(9)/1 were 9 (range 8-13), 12 (range 8-25) and 11 (range 9-16) and to platelets > or = 50 x 10(9)/1 were 11 (range 9-23), 13 (range 9-90) and 16 (range 13-99) in groups 1, 2 and 3 respectively. Patients in group 1 had a faster neutrophil recovery than patients in group 2 (P = 0.0002). The three patients who failed to engraft all received a combination of autologous peripheral blood and bone marrow cells.

Adolescent↗

The thrombin inhibitor, hirudin, attenuates lipopolysaccharide-induced liver injury in the rat.

The administration of gram-negative bacterial lipopolysaccharide (LPS) to rats results in hepatic parenchymal cell injury within 6 hr. The coagulation system is critical to the pathogenesis, but previously reported results suggested that its critical role is independent of insoluble clot formation and that thrombin may be a key mediator of liver injury. To test the hypothesis that thrombin is involved in LPS-induced liver injury, animals were treated with the selective thrombin inhibitor, hirudin. The hirudin treatment regimen effectively inhibited thrombin, as evidenced by prolonged activated partial thromboplastin time and by maintenance of plasma fibrinogen concentrations in LPS-treated rats. Treatment with hirudin prevented LPS-induced liver injury, assessed by plasma alanine aminotransferase activity and histological evidence of hepatocellular necrosis. Previous studies have shown that LPS exposure results in the accumulation of neutrophils and platelets within the liver and that both of these cell types are critical for the development of LPS-induced liver injury. Hirudin attenuated in part the decrease in blood platelet concentration that accompanied LPS administration, but did not alter hepatic platelet or neutrophil accumulation. These results support the hypothesis that thrombin is required for hepatic injury from LPS exposure, but that it does not act by promoting the accumulation of platelets or neutrophils within the liver.

Animals↗

Reducing the risks: adolescents and sexually transmitted diseases.

The incidence of sexually transmitted disease (STDs) in adolescents is alarming and continues to increase. Prevention and treatment of STDs in this population are impeded by the lack of accessible services which address the unique needs of teens. Nurse practitioners who provide services to teens should be knowledgeable about adolescent development and how to provide "teen-friendly" services. This article describes how adolescent development affects the incidence, prevention, and treatment of STDs. Approaches to the care of the adolescent client are described.

Adolescent↗

High-dose therapy and autologous stem cell rescue for poor risk and refractory lymphoma: a single centre experience of 123 patients.

Over an 8-year period we autografted 123 patient with poor-risk lymphoma. Sixty-three patients had Hodgkin's disease (HD) and 60 non-Hodgkin's lymphoma (NHL). Of the patients with HD, 45 had responsive and 18 resistant disease prior to high-dose therapy. Fifty-three patients with NHL had responsive and seven had resistant disease at the time of transplantation. Seventy-seven patients received autologous bone marrow (BM) rescue, 39 autologous peripheral blood progenitor cell (PBPC) rescue, and seven combined BM and PBPC rescue. High-dose chemotherapy was BEM in 67, BEAM in 39, TBI and cyclophosphamide or etoposide or BCNU in 10, etoposide/mitozantrone in six and etoposide/melphalan in one. There was eight (6.5%) deaths due to treatment-related toxicity, within the first 100 days post-transplantation. Of the patients with HD 41 (65%) are alive at a median follow-up of 39 months (range 2-94). Thirty-three (52%) patients remain in CR. The median DFS of the 63 patients with HD is 34 months (95% CI 7-61). The median DFS for patients transplanted with responsive disease was significantly better than for those transplanted with refractory disease (61 vs 21 months P < 0001). Thirty-five (58%) of the patients with NHL are alive, and 20 (33%) remain in CR. The median DFS for patients transplanted with responsive and refractory disease was 11 months (95% CI 3-19) and 4 months (95% CI 0-9; P = NS) respectively. The median DFS for patients transplanted with HD was significantly better than for patients transplanted with NHL (34 vs 8 months, P < 0.002). In both groups there was no significant difference in DFS in patients receiving one, two, three or more lines of therapy prior to transplantation. In summary, in patients with poor-risk lymphoma who have responsive disease high-dose therapy may result in durable CRs. Conversely, only a small proportion of patients with HD or NHL with resistant disease achieve CR after autologous stem cell rescue.

Adolescent↗

Measurement of reticulated platelets following peripheral blood progenitor cell and bone marrow transplantation: implications for marrow reconstitution and the use of thrombopoietin.

Neutrophil and platelet engraftment times are significantly shorter in patients undergoing PBPCT compared with ABMT. The explanation for this is unclear. The reticulated platelet percentage (RP%) has been established as a measure of bone marrow platelet production. Using this measurement we have followed thrombopoiesis over the transplant period in 10 patients undergoing PBPCT, eight ABMT and four alloBMT. Neutrophil and platelet engraftment times were significantly shorter in patients undergoing PBPCT than either ABMT or alloBMT. The RP% fell to a nadir in parallel with the platelet count in all patients following conditioning therapy consistent with an aplastic state and rose before platelet recovery as young platelets were released. The peak rise in the RP% was significantly greater and occurred earlier in PBPCT compared with BMT. The total number of reticulated platelets released during the time of engraftment was significantly greater in PBPCT than BMT. The potential role of the RP% in the timing of thrombopoietin therapy is explored. Finally the diagnostic use of the RP% in post-transplant thrombocytopenia is illustrated by a case in which a persistently high RP% accurately predicted a consumptive aetiology.

Adolescent↗

Improved yield of peripheral blood progenitor cells on the Cobe Spectra.

The efficiency of leucapheresis using the Cobe Spectra depends on the observation of the operator to monitor the haematocrit (Hct) in the collection line at the recommended Hct of 1%. Cells were harvested by processing 3 x total blood volume (TBV) over 3-4 h. During the harvest the manual Hct and the colony-forming units granulocyte-macrophage (CFU-GM) concentrations were analysed in the collection line in the observed Hct range of 1-7.5%. There was a correlation between the manual and observed Hct (r = 0.97). The CFU-GM concentration was normalised to allow comparison between patients. The increase was statistically significant between 1-2% (P = 0.04) and 1-3% Hct (P = 0.05). The increase in CFU-GM concentration remained at the termination of harvest, indicating that not all available CFU-GM were harvested. The optimum concentration of progenitor cells was found to be at 3% Hct. We postulate that this may permit the collection of sufficient cells on one occasion to allow PBPC autografting in the majority of patients who respond to mobilisation.

Adult↗

Cat scratch disease: detection of Bartonella henselae DNA in archival biopsies from patients with clinically, serologically, and histologically defined disease.

Serological and epidemiological studies suggest that Bartonella henselae is the etiological agent of cat scratch disease. We designed a study to detect B. henselae in archival biopsies by polymerase chain reaction amplification of the 16S rRNA gene followed by Southern blot hybridization. Forty-two histologically defined cat scratch disease biopsies and eighteen controls were selected for blinded analysis. After testing, charts were reviewed for clinical, immunological, and microbial evidence of infection. Results were correlated with duration of illness and antimicrobial therapy. B. henselae DNA was identified in 27 of 42 (64%) histologically defined patients and 23 of 34 (68%) patients defined both clinically and histologically. There were no false positives (0 of 18). A small subset (n = 14) had cat scratch disease serological tests performed. B. henselae was identified in 8 of 10 serologically positive patients. Polymerase chain reaction detected 50% of our DNA-positive cases (most of these early in the clinical course). Southern blotting of amplicons both doubled sensitivity (detecting patients > 4 weeks into illness) and confirmed B. henselae as the causative species. Our study strongly associates B. henselae with cat scratch disease, suggesting that it may be the most likely etiological agent in the majority of patients with cat scratch disease.

Adolescent↗

Plastic-adherent progenitor cells in mobilized peripheral blood progenitor cell collections.

The use of peripheral blood progenitor cells (PBPC) to reconstitute hematopoiesis after high-dose chemoradiotherapy is now commonplace in the treatment of malignancies. Attempts to characterize these cells have concentrated primarily on their phenotype and their content of clonogenic colony-forming cells (CFC). We have used a plastic-adherent delta (P delta) assay system to evaluate the quantity and quality of more primitive cells in addition to the conventional measurements of CFC and CD34-positive cells. The leukapheresis products from 20 patients mobilized using cyclophosphamide (Cy) and granulocyte colony-stimulating factor (G-CSF) were examined for progenitor cell content. The mean number of mononuclear cells (MNC), colony-forming units-granulocyte/macrophage (CFU-GM), and CD34-positive cells from two leukaphereses per patients were 7.9 x 10(8)/kg, 47.3 x 10(4)/kg, and 10.5 x 10(6)/kg, respectively. The mean number of P delta progenitors was 9.3 x 10(4)/kg. Limiting dilution analyses showed the frequency of P delta progenitors in PBPC to be between 1 and 5.3 per 10(5) MNC and that each P delta progenitor has the proliferative capability to generate an overall mean of 4.5 CFU-GM. Of the 20 patients, 16 underwent autografting with PBPC alone. Fifteen patients engrafted neutrophils and platelets within 16 days. One patient had delayed engraftment associated with inadequate etoposide clearance. Statistical analysis showed a strong correlation between numbers of CFU-GM and CD34 positivity. The numbers of plastic-adherent P delta progenitor cells did not correlate with CFU-GM or CD34-positive cells. We conclude that the plastic-adherent P delta progenitor cell assay is capable of measuring primitive hematopoietic cells and that it may be useful for the investigation of primitive progenitors in PBPC harvests.

Antigens, CD34↗

Rhodococcus equi--an increasingly recognized opportunistic pathogen. Report of 12 cases and review of 65 cases in the literature.

Rhodococcus equi, a gram-positive, weakly acid-fast coccobacillus, initially isolated from horses, is becoming increasingly recognized as an important pathogen for immunosuppressed human hosts since the first human case was reported in 1967. A review of the English medical literature yielded 53 cases. During the last 11 years, the microbiology laboratories of the authors isolated the organism from 12 patients. Of the total 65 cases, 60 occurred in immunosuppressed patients with HIV infection, malignant neoplasms, or chronic immunosuppressive therapy. The lung is the most common primary site of infection. Typically, the lesion is densely infiltrated by histiocytes with multiple microabscesses. Intracellular gram-positive coccobacilli are easily demonstrated. R equi grows well on routine non-selective media at 35 degrees C. Previously, many cases may have been missed because the organism resembles oropharyngeal commensal diphtheroids. Clinical information with gram and Kinyoun strains on fresh isolates is helpful in recognizing the possibility of R equi infection.

Acquired Immunodeficiency Syndrome↗

Probability of progenitor renewal (PPR) and production of clonogenic progeny (CFU-GM) by primitive adherent progenitor cells in adult human bone marrow and umbilical cord blood.

Human haemopoietic tissues contain primitive plastic-adherent progenitor cells (P delta cells) that can be detected by measurement of their granulocyte-macrophage colony-forming cell (CFU-GM) progeny. Limiting dilution analysis and Poisson statistics are necessary for determining the frequency of P delta cells because each of them produces several CFU-GM. Limiting dilution also permits measurement of the abilities of individual P delta progenitors to produce CFU-GM. Here we report that the frequencies of P delta progenitors in cord blood and adult marrow are similar (5.6 and 7.8/10(5) mononuclear cells respectively) and individual cord blood P delta progenitors produce fewer CFU-GM than adult P delta progenitors. To test the possibility that the lower production of differentiated progeny by cord blood cells was the result of a higher rate of self-renewal, we devised a two-stage limiting dilution assay relying on the relative production of CFU-GM after two consecutive weeks of incubation. The probability of progenitor renewal (PPR) was derived from the number of wells (progenitors) that produced CFU-GM on both occasions compared with the number that produced CFU-GM on the first occasion only. The total number of CFU-GM produced on the second occasion compared with the number produced on the first occasion provided an index of the overall change in the size of the P delta cell population. The data indicate that P delta cells in cord blood have a higher PPR (0.59) than those in adult marrow (0.36). Also, the relative numbers of CFU-GM produced in the second and first weeks were greater for cord blood (1.2) than for adult marrow (0.36). Therefore P delta cells in cord blood have a greater capacity for self-maintenance and possibly for expansion than P delta cells in adult marrow.

Adult↗

Peripheral blood progenitor cell harvesting in multiple myeloma and malignant lymphoma.

Peripheral blood progenitor cells are being used increasingly as part of the treatment protocol for a variety of haematological malignancies. The most appropriate mobilisation therapy and the optimum collection procedures have yet to be fully elucidated. 28 patients with myeloma (9), NHL (11) and HD (8) underwent PBSC mobilisation and harvesting between November 1992 and October 1993. Two protocols were used; the myeloma group received high-dose cyclophosphamide, 7 g/m2 + G-CSF and were leucapheresed on 5 consecutive days during the recovery period using the Haemonetics V50 and the lymphoma group a lower dose of cyclophosphamide, 3 g/m2 + G-CSF followed by leucapheresis on 2 or 3 occasions using a Cobe Spectra. Median time to achieve a WBC of 1 x 10(9)/l during the recovery phase, was 14 days (11-16) and 10 days (9-15) respectively. Median numbers of MNC and CFU-GM collected for the myeloma group were 5.9 x 10(8)/kg (2.5-13.5) and 69.4 x 10(4)/kg (9.9-268.1) and for the lymphoma group. 5.1 x 10(8)/kg (1.2-11.1) and 35.4 x 10(4)/kg (1.2-129.7). Three patients with lymphoma had a low yield of CFU-GM, two of which did not proceed to autograft. The third patient failed to engraft and died despite receiving bone marrow backup. For the remaining 25 patients, median time to neuts > 0.5 x 10(9)/l and platelets > 50 x 10(9)/l was 9 (8-13) and 11 (9-23) days for the myeloma group and 12 (9-15) and 13 (9-180) days for the lymphomas. We found a strong correlation between CD34+ cells and CFU-GM from the last 9 patients. There is a correlation between CFU-GM infused and speed of engraftment. All patients who received > 10 x 10(4) CFU-GM/kg showed a rapid engraftment for neutrophils and platelets. In all cases, when > 4 x 10(8)/kg MNC were harvested, > 10 x 10(4) CFU-GM/kg were obtained. Sufficient cells for a rapid engraftment can be obtained from 2 leucaphereses in the majority of patients. The recovering peripheral blood WBC provides a good indicator of when to harvest. The target value of CFU-GM can be predicted by the number of cells harvested and by the number of CD34 positive cells in the leucapheresis product.

Aged↗

Peripheral blood stem cell transplantation after high-dose therapy in patients with malignant lymphoma: a retrospective comparison with autologous bone marrow transplantation.

We report the results of peripheral blood progenitor cell (PBPC) harvesting in 22 patients with lymphoma who underwent leucapheresis after cells were mobilised using 3 g/m2 cyclophosphamide and G-CSF. In 19 patients, the total CFU-GM collected was greater than 7.5 x 10(4)/kg. These patients underwent successful autologous PBPC transplantation. This group of patients was compared to a historical group of 24 patients with lymphoma who underwent ABMT with the same conditioning chemotherapy. The time to engraftment of neutrophils to 0.5 x 10(9)/l was significantly reduced (median 11 days vs 19 days, P < 0.0001) and consequently in-patient stay was reduced (median 21 days vs 28 days, P < 0.001). Blood product support (median 3 vs 4 units blood, P = 0.02; median 15 vs 40 units platelets, P = 0.005) and use of TPN (median 0 days vs 8 days, P < 0.001) were reduced. We estimate a saving of approximately pounds 2370 per patient using PBPC for autologous transplantation compared to bone marrow progenitor cells. This saving is significant (P < 0.001).

Adult↗

Comparative treatment of mares susceptible to chronic uterine infection.

Four intrauterine treatment strategies were evaluated for effectiveness in mares that were confirmed to be susceptible to chronic uterine infection. Pretreatment samples were obtained at detection of estrus, and a genital strain of Streptococcus zooepidemicus was infused into the uterus when a preovulatory (> 35 mm) follicle was detected. At 12 hours after inoculation, mares were assigned to 1 of 4 selected treatment groups: autologous plasma, 100 ml (n = 5); potassium penicillin, 5 million U in 100 ml of phosphate-buffered saline solution (PBSS; n = 5); 10 mg of prostaglandin F2 alpha in 100 ml of PBSS (n = 5)' and large-volume lavage with normal saline solution (1,000 ml increments). A fifth group, treated with vehicle alone (100 ml of PBSS), served as a negative control (n = 7). All treatments were administered into the uterus. To assess the effectiveness of the treatment, samples for culture and cytologic examination were collected at 96 hours after bacterial inoculation. An effect of treatment was observed on the number of uterine neutrophils (P = 0.02) and growth of S zooepidemicus (P < 0.01). Intrauterine treatment with potassium penicillin, prostaglandin F2 alpha, and large-volume uterine lavage significantly reduced the growth of S zooepidemicus (P < 0.01) as well as the number of neutrophils (P < 0.02). Autologous plasma reduced the number of neutrophils (P < 0.05), but not growth of S zooepidemicus. There was significant correlation between the number of uterine neutrophils and growth of S zooepidemicus for each treatment group (r = 0.57; P < 0.05).

Analysis of Variance↗