Tumor Vasculature in Young and Old Hosts: Scanning Electron Microscopy of Microcorrosion Casts with Microangiography, Light Microscopy and Transmission Electron Microscopy

Tumor growth in vivo is dependent upon new blood vessel formation. When B16-F10 melanoma cells are implanted subcutaneously in young (3 mo) and old (24 mo) C57BL/6 mice the rate of growth is dependent on the age of the mice. This study involved a wide range of histological and microscopic techniques but was limited primarily to the initial phase of tumor growth. Stereological point counting from light microscopy (LM) of standard histological sections has been used to yield data regarding blood content. Tumor-bearing mice were perfused through the aorta with a fixation solution and were infused with a low-viscosity radiopaque gel (Microfil) or resin (Mercox). Soft x-rays of the whole animal were used for identifying the feeding vessels to the tumor. Tumors with Microfil were sliced and used for microangiography and light-microscopic observation while those with resin were used to make corrosion casts for scanning electron microscopy (SEM). The different characteristics of the tumor blood vessels in different aged mice were most obvious through SEM of vascular corrosion casts. In comparison with tumors in young mice those of similar size in old hosts had more necrosis, reduced presence of angiogenic features, decreased vessel density, reduced penetration into the tumor, and enhanced tortuosity of the vessel lumen. Transmission electron microscopy (TEM) revealed incompletely developed wall structure of the vessels regardless of host. The above results are consistent with the hypothesis that retarded angiogenesis may be responsible in part for the limited growth of tumors in old hosts

Mechanisms of Unexplained Anemia in the Nursing Home

To characterize anemia in elderly nursing home residents. Design : Prospective multiinstitutional cohort study. Setting : Five nursing homes. Participants : From retrospective analysis, residents found to be anemic using chart review were prospectively randomized. Of the 81 residents enrolled, 60 were anemic. Measurements : Chart review for medical history and factors related to treatment or history of anemia, extensive laboratory evaluation for causes of anemia, and classification of anemia by two hematologists. Results : Among the 60 anemic residents, the causes of anemia were idiopathic (n=27), iron-deficiency (n=14), anemia associated with chronic disease (n=8), anemia of renal insufficiency (n=6), and other (n=5). The eryrthropoietin (EPO) response to anemia was lower in residents with idiopathic anemia (IA) than in those with iron-deficiency anemia, and this correlated with renal function as estimated using calculated creatinine clearance. In this elderly population, advancing age was not correlated with lower EPO response. Conclusion : IA is common in nursing home residents. A lower EPO response contributes to the high prevalence of anemia in this setting and may be due, in part, to occult renal dysfunction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65745/1/j.1532-5415.2004.52116.x.pd

Pneumococcal Vaccination and Revaccination of Older Adults

As individuals advance in age, the risk of infection, bacteremia, and mortality caused by Streptococcus pneumoniae rises. Retrospective data demonstrate that the licensed penumococcal polysaccharide vaccine (PPV) is effective in older persons in reducing serotype-specific invasive disease. PPV demonstrates good immunogenicity in older adults, generally comparable to that in younger subjects, although certain cohorts respond less well. The response to PPV is T cell independent, however, and does not elicit immunologic memory. The duration of the anti-capsular polysaccharide antibody response appears to wane as early as 3 years after vaccination. In older persons, revaccination induces an antibody response, although it may not be as strong as that from the initial vaccine. While revaccination of older adults has been recommended, clinical efficacy has not yet been proven. Measures of antibody function may be at least as important in determining protection as are quantitative antibody levels. Additional studies of immunogenicity, particularly regarding revaccination, will facilitate the design of an optimal pneumococcal vaccination policy. Research into conjugate- and protein-based pneumococcal vaccines, which elicit T-cell-dependent responses and induce immunologic memory, is needed in older persons. In the meantime, administering to PPV to recommended groups should be a public health priority

Going Skin Deep: A Case of Nodulo-Pustular Lesions in Acute Myeloid Leukemia

Case description: A 59 year old female with acute myeloid leukemia M7 variant presented with one week of progressive facial, head, and neck lesions preceded by a small right thigh macular lesion that had developed into a larger papulo-pustular lesion. Subsequently, a number of similar papular lesions erupted across her forehead and grew into painful nodulo-pustular lesions. Associated right sided periorbital edema prompted her hospitalization. She has a history of recurrent upper respiratory infections, pulmonary aspergillosis, staphylococcus epidermidis vertebral osteomyelitis, diabetes mellitus, and genital herpes. For AML, she had received two remission induction cycles of idarubicin/cytarabine, then high dose ara-C five months prior to admission. For persistent neutropenia, she required daily granulocyte-colony stimulating factor. Other medications included carvedilol, lisinopril, gabapentin, lorazepam, oxycodone, and valacyclovir. Admission vital signs were unremarkable. Examination revealed cervical lymphadenopathy and multiple nodulo-pustular lesions scattered across the forehead and neck, with a similar lesion on her right thigh. Lesions ranged from papules with surrounding erythema to 2 cm indurated erythematous nodules with central ulcerations and drainage. Right sided periorbital edema was present without visual field deficits, conjunctival injection, or extraocular movement pain. Labs included: WBC 3,720 with ANC of 2,976, hemoglobin 9.4 g/dL, platelets of 80,000, HCO3 21 mEQ/L without anion gap, glucose 115 mg/dL, and lactate 1.5 mEq/L. A skin biopsy was obtained, and IV vancomycin, acyclovir and voriconazole were initiated due to concern for superinfection. Lesions continued to progress to pustules that eventually crusted. Biopsy revealed acute neutrophilic dermatitis. Antibiotics were discontinued and prednisone was initiated with further improvement. Two months later, she was rehospitalized for bilateral pneumonia with skin lesion recurrence, now on her chest and left wrist. Skin biopsy again confirmed acute neutrophilic dermatitis. Discussion: Sweet Syndrome is associated with acute myeloid leukemia. Though typically presenting as well-demarcated papules and plaques with surrounding erythematous base, this presentation was atypical, as lesions were predominantly nodulo-pustular. She had multiple risk factors for Sweet Syndrome that may have contributed including chronic intermittent upper respiratory infections. Even after she steroid treatment at initial presentation, she had recurrence in the setting of pneumonia, suggesting an infectious precipitant. She also received daily tbo-filgrastim, a growth factor associated with Sweet Syndrome when neutrophils rapidly increase. The patient’s M7 variant of AML also provides a unique aberration that may have made her more susceptible. In patients with a combination of risk factors including URIs, AML, and G-CSF use, Sweet Syndrome may present atypically. Skin biopsy should be considered in such patients to confirm diagnosis and initiate appropriate treatment with corticosteroids

Immune Alterations in Healthy and Asthmatic Adolescents Induced by Final Examinations

Immune responses to an academic stressor were examined in healthy and asthmatic adolescents with regard to their illness symptom reports. Eighty-seven high school students completed a health diary for 2 weeks and provided three blood samples during midsemester, final-exam, and postexam periods. During exam week, all students showed significant immunological alterations from baseline: Natural killer cell activity was significantly lower, whereas lymphocyte proliferation and neutrophil superoxide release were significantly higher. These immune changes tended to return toward baseline during the postexam period, but the enhanced neutrophil reactivity continued to rise. Overall, immunological responses were similar between asthmatic subjects and controls. Appropriate medical management may have accounted for this similarity. However, subtle group differences in the postexam recovery pattern and a continuous activation of inflammatory cell function following a stressor may warrant further investigation