Phagocyte function and cytokine production in community acquired pneumonia.

BACKGROUND--It is possible that many deaths from pneumonia may involve the generation of inflammatory mediators and tissue damage by activated phagocytes. To test this hypothesis phagocyte function, plasma levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha), and soluble interleukin 2 receptor (IL-2R), disease severity, and outcome have been examined in 46 patients with community acquired pneumonia. METHODS--Polymorphonuclear leucocyte (PMNL) and monocyte function were measured daily by chemiluminescence in these patients during the first week of admission, and cytokine levels were subsequently determined by ELISA. A series of 61 healthy individuals were used as a control group for the chemiluminescence results. RESULTS--There was evidence of phagocyte, particularly PMNL, activation on admission in 76% of the patients. Most patients (86%) also had raised IL-2R levels on admission. IL-6 and unbound TNF alpha were present in 23% and 41% of patients at varying times during the course of the disease. There was little correlation between measurements of cytokine or phagocyte levels and outcome or indicators of disease severity, although this may be because of the small number of patients included in this preliminary study. CONCLUSIONS--These results are consistent with the hypothesis that activated phagocyte function and raised levels of circulating cytokines may contribute to the pathogenesis of community acquired pneumonia. There are striking similarities in this respect between pneumonia, adult respiratory distress syndrome, and sepsis.     

Effects of treatment on the histopathology of leprosy.

AIMS--To identify the histological changes in leprosy skin lesions over the first few weeks after the start of leprosy treatment and to examine their relationship to reversal reaction. METHODS--Sequential skin biopsy during treatment with multiple drug therapy. In this study, a series of 28 patients was studied, from whom two or more biopsies were taken at two week intervals. Fourteen patients had paucibacillary leprosy (PBL) and 14 had multibacillary leprosy (MBL). RESULTS--In most cases, granuloma fraction and bacterial index fell during treatment, the bacterial index being less sensitive than the granuloma fraction. Since the biopsies were fixed in buffered formalin and processed through to paraffin wax, little immunohistochemistry was feasible. However, there was strong evidence of immune activation, with increased expression of HLA-DR in the granulomas of MBL and PBL cases: the epidermis also expressed HLA-DR in several patients. Such changes may reflect gamma IFN production from granuloma lymphocytes. Patients with reversal reaction often showed HLA-DR expression on admission which decreased with corticosteroid treatment. CONCLUSIONS--The results suggest that activation of cell mediated immunity in leprosy lesions occurs during treatment with multiple drug therapy and may not be restricted to those with clinical evidence of reversal reaction.     

The influence of killed Mycobacterium leprae and other mycobacteria on opsonized yeast phagocytosis.

The influence of killed mycobacteria on the metabolic burst associated with phagocytosis of opsonized zymosan by normal human polymorphonuclear leucocytes (PMNL) or monocytes was studied by chemiluminescence (CL) measurements. M. leprae reproducibly reduced the peak and total CL of both types of phagocyte to a small, but highly significant extent. Electron microscopy showed that M. leprae were phagocytosed: cells with ingested or adherent M. leprae phagocytosed fewer zymosan particles. M. leprae did not cause aggregation of the phagocytes or quenching of CL. M. lepraemurium did not influence the CL response to zymosan. Addition of M. tuberculosis caused an increased response with PMNL but not with monocytes.     

Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology,DNA content,and chromatin texture

A number of noninvasive fiber optic optical technologies are under development for real-time diagnosis of neoplasia. We investigate how the light scattering properties of cervical cells are affected by changes in nuclear morphology, DNA content, and chromatin texture, which occur during neoplastic progression. We used a Cyto-Savant computer-assisted image analysis system to acquire quantitative nuclear features measurements from 122 Feulgen-thionin-stained histopathologic sections of cervical tissue. A subset of the measured nuclear features was incorporated into a finite-difference time-domain (FDTD) model of cellular light scattering. The magnitude and angular distribution of scattered light was calculated for cervical cells as a function of pathologic grade. The nuclear atypia strongly affected light scattering properties. The increased size and elevated DNA content of nuclei in high-grade lesions caused the most significant changes in scattering intensity. The spatial dimensions of chromatin texture features and the amplitude of refractive index fluctuations within the nucleus impacted both the angular distribution of scattering angles and the total amount of scattered light. Cellular scattering is sensitive to changes in nuclear morphology that accompany neoplastic progression. Understanding the quantitative relationships between nuclear features and scattering properties will aid in the development of noninvasive optical technologies for detection of precancerous conditions.     

Merkel cell tumour: case reports and review

Merkel cell carcinoma, a small-cell undifferentiated/neuroendocrine carcinoma, is a highly invasive primary malignant neoplasm of the skin that may arise from Merkel cells or an epithelial precursor cell. One tenth of all cases affect the eyelids and periocular region, typically in the elderly population. The presentation is generally as a painless erythematous nodule with telangiectatic blood vessels and often intact overlying skin. The rarity of Merkel cell carcinoma of the eyelid can lead to delay in diagnosis and treatment of this tumour. In the present paper, the authors illustrate the aggressive nature of Merkel cell carcinoma, and the importance of early and wide surgical treatment and close follow-up. They discuss the role of rapid paraffin histology compared to frozen section. METHODS: Three cases are described, discussing the clinical presentation, diagnosis and treatment, with a review of the pathology. RESULTS: All three patients were female, presenting with rapidly growing upper eyelid tumours 20 mm in size; one case had paraffin sections suggesting incomplete clearance when frozen section had appeared clear; exenteration was required. The other two cases had lymph node involvement at one and two months post wide local excision. All patients remain alive at follow-up of 6, 4.6, and 2 years, respectively. DISCUSSION: The cases illustrate the aggressive nature of the tumour, the unusual tarsal involvement and the typical pathology. Sampling errors associated with limited frozen section control of excision may be avoidable by the use of rapid paraffin histology. The highly invasive nature of this tumour requires close follow-up following resection.     

Heterogeneity ofin vitro chemosensitivity in perioperative breast cancer cells to mitoxantroneversus doxorubicin evaluated by a microplate ATP bioluminescence assay

Summary Apart from clinical trials, mitoxantrone (MX) is rarely used in breast cancer (BC) due to the anticipated anthracycline cross-resistance. We have examined this drug versus doxorubicin (DOX) using data obtained fromin vitro microplate ATP tumor chemosensitivity assays (ATP-TCA) of BC cells which were derived from 55 chemotherapy-naive patients at time of primary surgery. Both drugs were tested at 6 different concentrations ranging from 6.25% to 200% peak plasma concentrationin vivo (PPC). Differences between DOX and MX observed for mean IC₅₀, IC₉₀, and a sensitivity index (SI) were not statistically significant.In vitro response rates were 44% for DOX and 52% for MX. 34 of 52 eligible assays (65%) showed comparable activity of both drugs whereas a lack of cross-resistance was observed in the remaining 18 (35%) tumors as indicated by differences for SI. Cumulative concentration-response plots of tumors respondingin vitro with a 50 percent or 90 percent tumor cell inhibition showed a strong dose-dependence for both DOX and MX at concentrations which normally can be achieved within clinical tumors (i.e. 6.25%-50% PPC). At higher concentrations, however, cytotoxicity of DOX and MX could not be improved by furtherin vitro dose escalation. Moreover, a substantial proportion of BC specimens (DOX: 48.1%; MX: 40.4%) did not experience a 90 tumor cell inhibition at 200% PPC. In conclusion,in vitro results obtained by ATP-TCA indicate that there is no cross-resistance between MX and DOX in a substantial proportion of BC patients. This may be clinically useful and suggests that combinations including MX should be tested in patients clinically resistant to DOX containing regimens. Since both drugs produced sigmoidal concentration-response curves, dose escalation beyond a certain point may not produce increased sensitivity.     

Dengue in Grenada.

OBJECTIVES: Dengue fever is endemic in the country of Grenada and is grossly underreported as a source of morbidity. The goal of this study was to assess the status of dengue fever in a representative community in Grenada. METHODS: Surveys were conducted in the Mont Tout/Grand Anse Valley area in the parish of St. George's from March to June 1996. The objectives of the survey were to: (1) to assess the knowledge, attitudes, and practices (KAP) of residents; (2) to determine the presence of larval and adult Aedes aegypti and their potential breeding sites; and (3) to identify the seroprevalence of specific immunoglobulin G (IgG) dengue antibodies in the local population. RESULTS: Out of the 102 respondents to the KAP survey, 100 of them (98%) reported never having had dengue fever. Of the 75 persons who agreed to have blood samples taken, 70 of them (93%) (95% confidence interval = 85.1%-97.8%) tested positive with the IgG enzyme-linked immunosorbent assay, indicating past exposure. In terms of water storage, 98 of 102 respondents (96%) stored fresh water in containers. The vector survey found 57 of the 102 households (56%) had Ae. aegypti larvae in water containers on their property, and 94 of 102 dwellings (92%) had adult Ae. aegypti mosquitoes indoors. CONCLUSIONS: Although many people were familiar with dengue fever and mosquitoes, the 1996 survey found that their knowledge of the important relationships among mosquitoes, human behavior, and disease transmission was incomplete. Since 1996, continued education efforts have been made in the public school system and with national public health campaigns, yet little effort has been specifically targeted towards our study community. These data suggest Grenada has a need for continued community education that addresses dengue fever transmission and Ae. aegypti reduction.     

Identifying the emergence of the superficial peroneal nerve through deep fascia on ultrasound and by dissection: Implications for regional anesthesia in foot and ankle surgery

Regional anesthesia relies on a sound understanding of anatomy and the utility of ultrasound in identifying relevant structures. We assessed the ability to identify the point at which the superficial peroneal nerve (SPN) emerges through the deep fascia by ultrasound on 26 volunteers (mean age 27.85 years ± 13.186; equal male: female). This point was identified, characterized in relation to surrounding bony landmarks (lateral malleolus and head of the fibula), and compared to data from 16 formalin‐fixed human cadavers (mean age 82.88 years ± 6.964; equal male: female). The SPN was identified bilaterally in all subjects. On ultrasound it was found to pierce the deep fascia of the leg at a point 0.31 (±0.066) of the way along a straight line from the lateral malleolus to the head of the fibula (LM‐HF line). This occurred on or anterior to the line in all cases. Dissection of cadavers found this point to be 0.30 (±0.062) along the LM‐HF line, with no statistically significant difference between the two groups (U = 764.000; exact two‐tailed P = 0.534). It was always on or anterior to the LM‐HF line, anterior by 0.74 cm (±0.624) on ultrasound and by 1.51 cm (±0.509) during dissection. This point was significantly further anterior to the LM‐HF line in cadavers (U = 257.700, exact two‐tailed P < 0.001). Dissection revealed the nerve to divide prior to emergence in 46.88% (n = 15) limbs, which was not identified on ultrasound (although not specifically assessed). Such information can guide clinicians when patient factors (e.g., obesity and peripheral edema) make ultrasound‐guided nerve localization more technically challenging. Clin. Anat. 32:390–395, 2019. © 2019 Wiley Periodicals, Inc.