Assessment of a cytomegalovirus serology dual-testing strategy in hematopoietic stem cell transplant recipients.

BACKGROUND: Accurate determination of recipient cytomegalovirus (CMV) serostatus before allogeneic hematopoietic stem cell transplantation (HSCT) is critical, as it is the most important predictor of post-transplant CMV infection and remains associated with non-relapse mortality. The purpose of this study was to assess a recipient dual-testing strategy before HSCT. METHODS: CMV serologic testing was performed before allogeneic HSCT using 2 different assays: reference laboratory (RL) and American Red Cross (ARC). In all cases, blood samples were obtained for RL testing either before ARC testing (median 130 days before HSCT [range 12-2594]) or at the same time (median 25 days before HSCT [range 8-129]). The results of serologic testing were correlated with CMV viremia post HSCT. RESULTS: Of 287 recipients evaluated, 76 (26.5%) had discordant results, of which 74 (97.4%) tested RL-/ARC+. Ten had RL and ARC testing performed on simultaneously obtained samples, 3 of which (30%) were discordant (3 [100%] RL-/ARC+). Acute myeloid leukemia and receipt of blood product transfusion in the interval between testing were associated with RL-/ARC+ discordance. Correlation with viremia after HSCT suggested that RL-/ARC+ discordance was caused by detection of anti-CMV immunoglobulin transferred in transfused blood products and reduced specificity of the ARC assay. CONCLUSION: CMV-seronegative hematopoietic stem cell transplant recipients may be misclassified as seropositive if testing is performed after receipt of blood products or when using assays optimized for sensitivity at the expense of specificity. This misclassification may negatively affect post-HSCT outcomes for individual patients and studies that rely on accurate CMV serology reporting.

Effects of skyrin, a receptor-selective glucagon antagonist, in rat and human hepatocytes.

Peptidic glucagon antagonists have been shown to lower blood glucose levels in diabetic models (1-3), but attempts to identify small molecular weight glucagon receptor-binding antagonists have met with little success. Skyrin, a fungal bisanthroquinone, exhibits functional glucagon antagonism by uncoupling the glucagon receptor from adenylate cyclase activation in rat liver membranes (1). We have examined the effects of skyrin on cells transfected with the human glucagon receptor and on isolated rat and human hepatocytes. The skyrin used was isolated from Talaromyces wortmanni American Type Culture Collection 10517. In rat hepatocytes, skyrin (30 micromol/l) inhibited glucagon-stimulated cAMP production (53%) and glucose output (IC50 56 micromol/l). There was no detectable effect on epinephrine or glucagon-like peptide 1 (GLP-1) stimulation of these parameters, which demonstrates skyrin's selective activity. Skyrin was also evaluated in primary cultures of human hepatocytes. Unlike cell lines, which are largely unresponsive to glucagon, primary human hepatocytes exhibited glucagon-dependent cAMP production for 14 days in culture (EC50 10 nmol/l). Skyrin (10 micromol/l) markedly reduced glucagon-stimulated cAMP production (55%) and glycogenolysis (27%) in human hepatocytes. The inhibition of glucagon stimulation was a specific property displayed by skyrin and oxyskyrin but not shared by other bisanthroquinones. Skyrin is the first small molecular weight nonpeptidic agent demonstrated to interfere with the coupling of glucagon to adenylate cyclase independent of binding to the glucagon receptor. The data presented in this study indicate that functional uncoupling of the human glucagon receptor from cAMP production results in metabolic effects that could reduce hepatocyte glucose production and hence alleviate diabetic hyperglycemia.

Avermectins and flea control: structure-activity relationships and the selection of selamectin for development as an endectocide for companion animals.

Evaluation of a wide range of avermectin derivatives for flea activity in an in vitro feeding screen using the cat flea, Ctenocephalides felis, revealed a narrow structure-activity relationship (SAR) with activity surprisingly associated with monosaccharides and especially their C-5-oximes. We discovered commercially exploitable flea activity in a single compound, selamectin 33, which also possessed the necessary antiparasitic spectrum and margin of safety for development as a broad-spectrum companion animal endectocide.

Selamectin: a novel broad-spectrum endectocide for dogs and cats.

Selamectin, 25-cyclohexyl-25-de(1-methylpropyl)-5-deoxy-22, 23-dihydro-5-(hydroxyimino)-avermectin B1 monosaccharide, is a novel endectocide with a unique combination of efficacy and safety in dogs and cats following both oral and topical administration. The compound is active against fleas and ticks, intestinal hookworms and ascarids, and immature heartworms. Also it is well tolerated at higher dosages than 22,23-dihydroavermectin B1a (DHAVM) or milbemycin oxime in Collies, which is a breed known to exhibit idiosyncratic sensitivity to avermectins.

Malignant supratentorial ganglioglioma (ganglion cell-giant cell glioblastoma): a case report and review of the literature.

BACKGROUND: From both epidemiologic and pathologic viewpoints, gangliogliomas exhibiting components of giant cell glioblastomas are extraordinary neoplasms. We report herein the case of a 6-year-old girl who presented initially with a World Health Organization grade IV anaplastic ganglioglioma (a mixed ganglion cell tumor-giant cell glioblastoma). Despite aggressive management, the patient died of disease in a relatively short period. METHODS: Formalin-fixed, paraffin-embedded tissue blocks were sectioned at 5 microm for histochemical and immunohistochemical analyses. Hematoxylin-eosin-stained sections and immunohistochemically stained sections from the primary and secondary resections were reviewed. Reactivity for glial fibrillary acidic protein, neurofilament protein, synaptophysin, and Ki67 nuclear antigen was evaluated. RESULTS: Histologically, 2 distinct cell populations were noted on both the primary and secondary resections. The primary resection revealed a neoplasm having a predominant glial component consistent with a glioblastoma. Interspersed were dysmorphic ganglion cells supporting a diagnosis of ganglioglioma. The second resection (following therapy) demonstrated a much more prominent dysmorphic ganglion cell component and a subdued glial component. CONCLUSION: Although immunohistochemical analysis clearly distinguished the 2 tumor cell populations, the identification of Nissl substance in neurons proved to be equally helpful. Although other cases of grade III gangliogliomas and rare cases of grade IV gangliogliomas have been reported, the present case is exceptional in that, to our knowledge, it is the only report of a patient who presented initially with a composite grade IV ganglioglioma and who was clinically followed up to the time of death. This case allows direct comparison between the histologic findings in a giant cell glioblastoma and a ganglioglioma and documents the aggressive biologic behavior of this complex neoplasm.

Gingival microcirculation response to tooth brushing measured by laser Doppler flowmetry.

This study quantified changes in blood flow following tooth brushing, using laser Doppler flowmetry (LDF). Twenty subjects had polysiloxane stents fabricated with openings to permit placement of the LDF probe on the mesial papillae of 6 teeth. Probing depth, plaque index, and gingival index were recorded and subjects instructed in brushing. LDF initially recorded a 30 second baseline blood flow. The stent was removed and subjects brushed the site for either 3 or 10 seconds. The stent was repositioned and recordings again taken, followed by a control reading. The process was repeated 4 weeks later. Correlations between baseline and control readings were 0.585 (P < 0.001) at the first visit, and 0.654 (P < 0.001) at the return visit. The mean control blood flow was 156.4 perfusion units. The 3 and 10 second brushing increased the mean value 22.6 units and 21.2 units respectively (both P < 0.001). Tooth brushing for both 3 and 10 seconds significantly increased gingival blood flow in the papillary gingiva of healthy individuals.

Aspects of quality of dental hygiene care in supervised and unsupervised practices.

OBJECTIVE: The purpose of this study was to assess aspects of the quality of care provided by dental hygienists in a California demonstration project in which hygienists treated patients independent of dentists' supervision. METHODS: The structure and process of care were evaluated in nine independent practices using site visits and reviews of 25 records at each practice. The findings were compared to evaluations of six general dentist practices reviewed for a government agency and insurance company during the same time period. Patient satisfaction was assessed by a questionnaire. RESULTS: The structural aspects of the unsupervised hygienist practices were generally acceptable and surpassed the dentist practices in most areas, including infection control. For process, the hygienist practices had high percentages of acceptable care and were significantly better than the dentist practices in several areas, including follow-up to medical findings, updating the medical history at recall, and documenting the evaluation of the periodontal status and soft tissues. Ninety-eight percent of patients expressed satisfaction with their care in hygienist practices. CONCLUSION: Under the circumstances of the demonstration project and the methods used to assess the quality of care, the study showed that independent dental hygienist practice did not increase the risk to the health and safety of the public.

Characteristics of patients seeking care from independent dental hygienist practices.

OBJECTIVES: This study determined demographic characteristics, satisfaction with care, and likelihood of follow-up dentist visits for patients seen in office-based, independent, dental hygienist practices. METHODS: New patients were surveyed after their initial visits to independent hygienist practices to assess their demographic characteristics and satisfaction with care at both the beginning of practice operations and 18 months after the start of these practices. Follow-up surveys were sent to patients 12 and 24 months after their initial visits to the independently practicing dental hygienists to determine if patients had visited a dentist. RESULTS: Most respondents were white, female, had attended some college, and reported high family incomes. Ninety-eight percent of respondents were satisfied with their dental hygiene care. Follow-up questionnaires revealed that over 80 percent of respondents visited the dentist within 12 months of receiving dental hygiene care in independent settings. This level of follow-up care with dentists was found both for respondents who reported having a regular dentist at their initial visits with the hygienists and for those who reported not having a regular dentist. CONCLUSIONS: Independent practice by dental hygienists provided access to dental hygiene care and encouraged visits to the dentist.

In vitro study of the effects of Nd:YAG laser probe parameters on bovine oral soft tissue excision.

BACKGROUND AND OBJECTIVES: Lasers are now used for intraoral, soft tissue procedures. The effects of Nd:YAG probes on cutting efficiency and temperature rise were evaluated in vitro. STUDY DESIGN/MATERIALS AND METHODS: Three hundred twenty-micron 400-microns, 500-microns, and 600-microns probes were used to ablate bovine gingiva, mucosa, and tongue at various power and frequency settings. Thermocouples positioned under the subjacent cortical bone measured temperature rise. Tissue samples were evaluated histologically. RESULTS: Mean pooled temperature rise was 1 degree C at 3 W and 1.4 degrees C at 5 W. Excision width ranged from 0..63 mm to 0.79 mm at tested settings, cutting depths from 0.19 mm to 0.49 mm, lateral and deep coagulation from 0.27 mm to 0.62 mm. CONCLUSION: Temperature rise in bone was related to increased power. Cutting efficiency of laser probes was not significantly improved by increased power. Probes of 320 to 500 microns provided efficient cutting at 3 W and 5 W, thus reducing the potential for unacceptable temperature rise in bone.

Ranitidine therapy for esophagitis in children with developmental disabilities.

Esophagitis is common in children with cerebral palsy. Because histamine2-receptor antagonists such as ranitidine have not been uniformly effective, we treated disabled children with esophagitis with greater than usual doses. Endoscopy and pH monitoring were used to monitor dose and response to treatment. A dose of 9.3 +/- 0.9 mg/kg/day did not improve visual or microscopic esophagitis after 3 months. A dose of 14.8 +/- 3.9 mg/kg/day resulted in only slight microscopic improvement, but symptoms were improved. There was no correlation between esophageal reflux index at enrollment and either severity of esophagitis or response to treatment. Elevation of gastric pH by ranitidine was infrequent. These results affirm that pH monitoring does not reliably identify disabled children with reflux esophagitis nor does ranitidine reliably heal this disorder.

Practice characteristics of dental hygienists operating independently of dentist supervision.

PURPOSE: This paper presents business characteristics of ten experimental independent dental hygiene practices operating in California between 1987 and 1990. Sixteen dental hygienists participated in the experiment, the Health Manpower Pilot Project 139 (HMPP 139). HMPP 139 dental hygienists wanted to work independently in traditional office-based settings, institutional settings, and other arrangements. They worked in group and solo practices, on a full- or part-time basis. METHODS: Data were collected from the HMPP 139 practices on services provided, patient visits, fees charged, referrals to dentists, acceptance of Medicaid patients, and services to organizational clients. Data collection methods varied, depending on the question addressed. Surveys of dentists' offices provided data on fees and Medicaid policies for comparison with the independent dental hygiene practices. RESULTS: All experimental practices attracted new patients for each quarter in operation. These practices mostly provided prophylaxis treatments; however, a wide variety of services was provided. Fees charged in HMPP 139 office-based practices were less than comparable fees charged in dentists' offices. At least one-third of patients in the HMPP 139 office-based settings received a referral to or an opinion about a dentist from the dental hygienist. HMPP 139 practices were more available to Medicaid patients than were California dentists offices. Each experimental independent practice provided care to at least one client in a nontraditional setting. CONCLUSIONS: The HMPP 139 practices consistently attracted new patients. This suggests independent practice for dental hygienists may be a viable and flexible alternative if the practices can stabilize total patients at a sufficiently high level. An independent practice alternative might increase access to care, contain fees, and direct the flow of patients to dentists. Further study is needed to test these findings.

Aggressive natural killer cell lymphoma of the small intestine.

We report a case of aggressive non-Hodgkin's lymphoma of the small cell type arising in the small intestine and having a natural killer cell phenotype. Immunophenotyping of frozen tissue sections revealed a lack of reactivity with the pan-T-cell markers CD3 and CD5, and no reaction with B-cell markers. Positive staining was obtained with antibodies to CD2, CD7, and CD56. Molecular studies were negative for clonal T gamma, T beta and immunoglobulin heavy-chain gene rearrangements. Natural-killer-cell-associated cytotoxin was demonstrated by positive staining with an antibody to perforin, a protein present in the granules of large granular lymphocytes. Despite its indolent histologic appearance, the aggressive nature of this neoplasm was suggested by the expression of the activation markers CD38 and CD71, and the nuclear proliferation marker Ki67, and confirmed clinically by its rapid recurrence with extensive involvement of the pelvic organs, resistance to chemotherapy, and the short survival of the patient. Distinct from many Asian cases, Epstein-Barr virus genome was not detectable in the tumor. This case emphasizes the importance of recognizing non-Hodgkin's lymphomas with a natural killer cell phenotype as a distinct entity, both biologically and clinically.

Self-organizing systems across scales.

Over the past few years, ecologists have increasingly recognized the existence of strong self-reinforcing (or self-organizing) interactions within systems at a variety of scales. Positive feedback within food chains has been reported from terrestrial and aquatic ecosystems. Accumulating evidence supports the existence within communities of cooperative guilds - tit-for-tat relationships based on diffuse mutualisms and favored by environmental unpredictability. At the landscape level, both real world experience and models indicate that processes such as hydrology and the propagation of disturbance can be strongly self-reinforcing (i.e. the landscape structure supports the process, and vice versa). Hence the picture emerges of a hierarchy of self-organizing systems that span food chains, communities and landscapes/regions.

Comparison of a conventional probe with electronic and manual pressure-regulated probes.

We compared the accuracy, consistency, time, comfort, and cost of probing with a conventional hand probe (CP) with 3-mm banded markings, a manual pressure-regulated probe (MP), and two electronic probes (IP and FP). Twenty (20) examiners used all four probes on a test block to determine accuracy; measurements compared favorably to the reference block. Two calibrated examiners probed the Ramfjord teeth of 10 periodontal patients on maintenance regimens, six sites per tooth (n = 708), with all four probes; measurements were repeated after one week. Wilcoxon signed-rank test showed the CP measured more deeply (P < 0.0001) than MP, FP, and IP with mean differences of 0.40, 0.67, and 0.58 respectively. MP measured more deeply (P < 0.001) than FP and IP, with mean differences of 0.27 and 0.18 mm. There was no difference between FP and IP. Time (min:sec) required by one examiner to perform full mouth probing on six subjects (minimum of 26 teeth each) was CP = 3:59; MP = 4:18; FP = 6:16; and IP = 7:23. Subjects rated FP and IP as slightly more uncomfortable than CP or MP. Cost per 1,000 uses was computed based on available data. The IP and FP took longer to perform and cost more per procedure than did the CP and MP. Spearman rank-order correlation revealed that only probe depths measured by CP and MP were well correlated (rs = 0.67). Although some statistically significant differences were found between probes, no differences were considered to be of clinical significance when probing periodontally healthy or maintenance patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic monoarticular arthritis and acute pericardial tamponade in a child with Crohn's disease.

We describe a 7-year-old child who developed right knee arthritis unresponsive to nonsteroidal anti-inflammatory drug therapy. Additional rheumatologic disorders including pleuropericardial effusion with tamponade supervened before the recognition of Crohn's disease involving the colon. Suppression of all sites of inflammation resulted from corticosteroid therapy. Aspects of diagnosis and treatment of these extraintestinal components of inflammatory bowel disease are discussed.