Recent diarrhea is associated with elevated salivary IgG responses to Cryptosporidium in residents of an eastern Massachusetts community.

BACKGROUND: Serological data suggest that Cryptosporidium infections are common but underreported. The invasiveness of blood sampling limits the application of serology in epidemiological surveillance. We pilot-tested a non-invasive salivary anti-Cryptosporidium antibody assay in a community survey involving children and adults. MATERIALS AND METHODS: Families with children were recruited in a Massachusetts community in July; symptoms data were collected at 3 monthly follow-up mail surveys. One saliva sample per person (n = 349) was collected via mail, with the last survey in October. Samples were analyzed for IgG and IgA responses to a recombinant C. hominis gp15 sporozoite protein using a time-resolved fluorometric immunoassay. Log-transformed assay results were regressed on age using penalized B-splines to account for the strong age-dependence of antibody reactions. Positive responses were defined as fluorescence values above the upper 99% prediction limit. RESULTS: Forty-seven (13.5%) individuals had diarrhea without concurrent respiratory symptoms during the 3-month-long follow-up; eight of them had these symptoms during the month prior to saliva sampling. Two individuals had positive IgG responses: an adult who had diarrhea during the prior month and a child who had episodes of diarrhea during each survey month (Fisher's exact test for an association between diarrhea and IgG response: p = 0.0005 for symptoms during the prior month and p = 0.02 for symptoms during the entire follow-up period). The child also had a positive IgA response, along with two asymptomatic individuals (an association between diarrhea and IgA was not significant). CONCLUSION: These results suggest that the salivary IgG specific to Cryptosporidium antigens warrants further evaluation as a potential indicator of recent infections.

Depression in Ménière's disease: a systematic review and meta-analysis.

BACKGROUND: Ménière's disease is a debilitating chronic peripheral vestibular disorder associated with psychiatric co-morbidities, notably depression. METHODS: Database searches were performed to identify studies that assessed depression in Ménière's disease. Metrics used to diagnose depression were extracted, along with the prevalence of depression in each study. RESULTS: Fifteen studies from 8 different countries reported on 6587 patients. The weighted average age was 55.3 years (range, 21-88 years). Depression was measured by eight different scales, with Zung's Self-Rating Depression Scale used most often. A weighted proportion of 45.9 per cent of patients (confidence interval = 28.9-63.3) were depressed. Weighted averages (± standard deviations) of Beck's Depression Inventory and the Illness Behavior Questionnaire - Dysphoria were 8.5 ± 7.9 and 2.4 ± 1.7, respectively. CONCLUSION: The prevalence of depression in patients with Ménière's disease is nearly 50 per cent. Treating otolaryngologists should have a low threshold to screen and refer appropriately. Identifying and treating depression should allow for improvement of overall quality of life in patients with Ménière's disease.

Immunologic and cellular changes accompanying the therapy of pollen allergy.

We had found previously that children with ragweed hay fever were somewhat less symptomatic after preseasonal immunization with large doses of ragweed pollen extract than were placebo-treated children. To study further the immunologic changes which accompany immunotherapy, these children were treated again the following year. Each patient served as his own control. Serum blocking (IgG) antibody, measured by inhibition of antigen-induced leukocyte histamine release, was increased 20- to 40-fold after therapy. The anticipated postpollen season increase of serum reaginic (IgE) antibody, measured by passive sensitization of leukocytes from nonallergic donors, was suppressed. Instead, the mean titer was decreased after treatment. Total serum IgE levels, measured by radial radioimmunodiffusion assay, were higher than normal; were correlated with reaginic antibody titers; and also did not increase in the pollen season after treatment. The concentration of both IgE and reaginic antibody was lower in the older children, irrespective of treatment. Leukocyte response to ragweed antigen E and guinea pig anti-IgE antiserum was assessed by means of in vitro histamine release techniques. After treatment, the leukocytes of 21 patients were less sensitive (11 cases), or less reactive (10 cases), to antigen E. Response to anti-IgE antibody also was diminished after treatment. In four cases, neither anti-IgE nor antigen E induced histamine release, although both IgE protein and ragweed-specific IgE antibody were present in the patients' own sera. Clinical improvement was correlated best with decreased leukocyte sensitivity and leukocyte reactivity to ragweed antigen E. It appeared that decreased cell sensitivity was related to lower serum reaginic antibody levels. Decreased cell reactivity, in the presence of both IgE protein and IgE antibody in the serum, may indicate a change in cellular response mechanisms. These studies suggest that clinical improvement following specific immunotherapy must be the result of complex changes in the immunologic and cellular components of allergic disease.

Purification of human IgG4 subclass with allergen-specific blocking activity.

Blocking antibodies (bAb) induced by allergen immunotherapy are restricted to the IgG1 and IgG4 subclasses, with IgG1 predominating early and IgG4 coming later. Study of IgG4 bAb has been limited, in part, by the absence of a method to purify IgG4. We describe a rapid immunoaffinity chromatographic method for the purification of that subclass from whole serum. Starting serum (TR) contained 90 micrograms/ml Dactylis glomerata (orchard grass) pollen (DGP)-specific IgG4, measured by indirect ELISA. The blocking activity of TR was assayed in vitro on IgE-sensitized human basophils. Immunoadsorption on a strong-binding anti-IgG4 monoclonal antibody (mAb) removed about 90% of the total and allergen-specific IgG4 and nearly all of the blocking activity from TR. An IgG4-rich fraction was then obtained by absorption of several small volumes of TR on a weak-binding anti-IgG4 mAb column at neutral pH followed by elution with glycine-HCl buffer. The pooled eluates contained 82% IgG4, amounting to a 65-fold purification of the serum IgG4; the yield was approximately 30%. Nearly all the DGP-specific antibody was in the IgG4 component of the eluate. The blocking activity of the eluate was approximately equal to that of TR. Immunoblot patterns with the eluate and with TR on SDS-PAGE of DGP were nearly identical. This method thus provides a fully active, relatively pure IgG4 blocking antibody. Moreover, the results reinforce the importance of using a well-chosen mAb when purifying proteins by immunoaffinity chromatography.

Proposal of a four-dimensional model of social response.

Descriptive models of social response attempt to identify the conceptual dimensions necessary to define and distinguish various types of influence. Building on previous approaches, the authors propose a new response model and demonstrate that a minimum of 4 dimensions is necessary to adequately provide for such influence phenomena as conformity, minority influence, compliance, contagion, independence, and anticonformity in a single model. In addition, the proposed model suggests 5 potential types of response that have not been previously identified. These new types suggest directions for future research and theoretical development. Selected empirical evidence is reviewed in support of the validity and integrative power of the proposed model.

Antigenic peptides on the surface of Dirofilaria immitis microfilariae.

Various methods of radioiodination were employed to identify peptides on the surface of Dirofilaria immitis microfilariae. Optimum surface radiolabelling occurred with the lactoperoxidase-catalyzed reaction. Two major peptides of 16 and 14 kDa were labelled by this method. These peptides were soluble in Nonidet P-40, were not glycosylated, and showed no signs of disulfide linkages. These peptides were immunoprecipitated by sera from D. immitis-infected dogs, but not by sera from uninfected dogs or sera from dogs with potentially cross-reactive nematode infections. Analysis of the 14 and 16 kDa peptides by two-dimensional gel electrophoresis revealed that the 16 kDa peptide was a single unit with a pI of 5.25 whereas the 14 kDa band was composed of three individual peptides with pI values ranging from 5.6 to 6.1. Iodination by chloramine T resulted in the same panel of labelled peptides but suffered from poor efficiency of 125I incorporation. The viability of microfilariae labelled by the standard Bolton-Hunter method decreased by 50% following the reaction which resulted in the labelling of a variety of internal components.

Processing specificity for human voice stimuli: electrophysiological evidence.

Recent neuroimaging studies have provided evidence for localized perceptual specificity in the processing of human voice stimuli, paralleling the specificity for human faces. This study attempted to delineate the perceptual features of human voices yielding selective processing, and to characterize its time-course. Electrophysiological recordings revealed a positive potential peaking at 320 ms post-stimulus onset, in response to sung tones compared with fundamental-frequency-matched instrumental tones, when both categories were distracters in an oddball task. This voice-specific response (VSR) evoked under conditions different from those yielding positivity at that latency in other contexts, indicates the overriding salience of voice stimuli, possibly reflecting the operation of a gating system directing voice stimuli to be processed differently from other acoustic stimuli.

Quantitative and qualitative changes in the humoral response of dogs through the course of infection with Dirofilaria immitis.

The present study compared the humoral response of dogs which developed microfilaremic or occult forms of dirofilariasis following experimental infection with Dirofilaria immitis L3 larvae. Quantitative analysis by ELISA revealed that antibody levels to adult somatic (AS), excretory-secretory (ES), and microfilarial (MF) antigens were highest during the patent phase of infection in dogs with either form of dirofilariasis. Patent sera from dogs destined for occult infections contained anti-AS and anti-MF antibody concentrations of 1,572 and 1,004 micrograms/ml, respectively, while microfilaremic-bound dogs contained 1,044 and 906 micrograms/ml, respectively. Chronic sera (430 days post infection) from occult dogs contained anti-AS and anti-MF antibody levels of 982 and 600 micrograms/ml, respectively, which were higher than in microfilaremic dogs. The antibody response to ES antigen was generally 10-fold less in absolute antibody concentrations at all time points tested. Immunoperoxidase staining of antigens transferred to nitrocellulose revealed the presence of several antigenic proteins which were recognized by occult, and to a lesser extent or not at all, by microfilaremic dogs. Sera drawn from occult-bound dogs 280 days post-infection, a time corresponding to microfilarial clearance (transition phase), contained higher antibody activity to microfilarial proteins weighing 47.5, 42.0, 34.2, and 22.4 kilodaltons compared to the microfilaremic dogs. This difference in antigen recognition became more apparent during the chronic phase of infection.

Nephrectomy and vena caval thrombectomy in patients with metastatic renal cell carcinoma.

OBJECTIVES: To report out experience with performing nephrectomy and vena caval thombectomy in patients with metastatic renal cell carcinoma. METHODS: A retrospective review was performed of 15 patients who underwent surgical excision of the primary tumor and a caval thrombus and treatment of concurrent metastases between 1989 and 1995. The sites of metastases included lungs (n = 8), bone (n = 3), bulky retroperitoneal or mediastinal lymph nodes (n = 2), liver (n = 1), and contralateral adrenal (n = 1). The level of caval involvement was suprahepatic in 3 cases, retrohepatic in 2 cases, and infrahepatic in 10 cases. Three patients had an Eastern Cooperative Oncology Group performance score of 0, 11 had a score of 1, and 1 had a score of 2. Median follow-up was 17 months. RESULTS: Median operative time was 6.5 hours and median hospitalization was 10 days. Two patients required re-exploration for postoperative hemorrhage. There were no perioperative deaths. Four patients underwent surgery for resection of solitary metastases (1 lung, 2 spine, and 1 humerus); 2 of the 4 received adjuvant radiotherapy. Two patients received biologic therapy preoperatively, 3 received it both preoperatively and postoperatively, and 6 received it only postoperatively. The median time to initiation of postoperative biologic therapy was 48 days (range 25 to 110). Eleven patients are currently alive, 7 with no evidence of disease at a median follow-up of 17 months (range 6 to 66) and 4 with stable metastases at 14 months (range 4 to 22). Ten of the 13 symptomatic patients had improved performance scores after surgery. Four patients have died from metastatic disease: 2 from rapid progression at 2 and 5 months after surgery and the other 2 at 17 and 42 months. CONCLUSIONS: Nephrectomy and vena caval thrombectomy can be safely performed in selected patients with metastatic disease. Furthermore, in patients receiving biologic therapy, nephrectomy may enable a better quality of life and prolonged survival.

Management of urinary stones in the patient with spinal cord injury.

The main objective of the urologist treating patients with spinal cord injury is to preserve renal function. In order to minimize morbidity, all attempts must be made to maintain a low bladder pressure, sterile urine, and a non-obstructed drainage system. These patients remain at increased risk of infection and stone formation despite all clinical intervention. Diligence in routine follow-up and careful evaluations will provide the best possible results. In the face of urolithiasis, ESWL, percutaneous nephrolithotomy, and chemolysis are effective means of treatment with acceptable morbidity. With future technologic advancements and implementation of neurostimulators to improve the urodynamic profiles, the incidence of renal insufficiency, urolithiasis, and overall morbidity in patients with spinal cord injury is likely to decrease.

Development of a chemotherapeutic model for microfilaricidal drugs to Dirofilaria immitis.

Microfilariae obtained from in vitro culture of adult Dirofilaria immitis were inoculated into naive dogs and used to test the in vivo efficacy of the antimicrofilarial drug Dizan. Injection of 33 million microfilariae into a 3-month-old male beagle pup over a 5-day period resulted in a microfilaremia that peaked at 863 microfilariae per ml on day 30. Treatment with Dizan resulted in a rapid clearance of microfilariae from the peripheral circulation. Four additional male beagle pups that were each given a total of 31 million microfilariae over 100 days maintained an average of 25 microfilariae per ml for 2 months. Microfilaremias were monitored by ELISA, a modified Knott's method and selected blood chemistry tests. It was shown that after residing in the peripheral circulation the microfilariae were able to develop into infective larvae in mosquitoes; therefore, the system may be a reasonable model of the natural microfilaremic state.

Contagion: a theoretical and empirical review and reconceptualization.

We have reviewed theories and research in the area of contagion with an emphasis on definitions of contagion. The review shows that a great deal of the confusion surrounding the term is due to the fact that the phenomena involved in contagion are extremely heterogeneous, yet they typically have been placed under homogeneous rubrics. Accordingly, we propose herein that contagion should be conceptualized as a general type, social contagion, and three subtypes: disinhibitory, echo, and hysterical. In this article, we have distinguished social contagion and its subtypes from other types of social influence phenomena and reclassified theoretical and research articles under the newly proposed definitions. The proposed reconceptualization shows how contradictions in the literature can be resolved by distinguishing the type of contagion in question and provides the foundation for a more comprehensive and useful psychology of contagion.

Prevention of latex sensitization in guinea pigs by a bacterial and viral filter used in anaesthesia.

BACKGROUND: Preventing anaphylactic reactions as a result of natural rubber latex (NRL) proteins is an important concern in anaesthesia. The clinical relevance of a bacterial/viral filter (Pall BB25) in preventing sensitization to NRL by inhalation was tested in guinea pigs. METHODS: Guinea pigs (n=8-10 in each group) were exposed to aerosolized NRL-contaminated cornstarch powder or to NRL in saline for 1 h every day for 2 weeks. The experiments were repeated with a Pall BB25 filter placed over the aerosol system. Control groups were exposed to non-contaminated cornstarch or to saline alone. Three weeks after the last exposure, specific bronchial challenge was performed and thromboxane (Tx) B2 levels in bronchoalveolar lavage fluid were measured. RESULTS: After bronchial challenge, the animals exposed to NRL or NRL-contaminated cornstarch with the BB25 filter in place showed a level of bronchoconstriction (i.e. the variation of pulmonary insufflation pressure) not different from controls. Conversely, those exposed to NRL or NRL-contaminated cornstarch without the filter showed a higher level of bronchoconstriction (respectively, P<0.02 and P<0.001) than control. Elevated TxB2 levels were found in the lungs of the guinea pigs, which inhaled NRL or NRL-contaminated cornstarch in the absence of a filter. Animals treated with the filter showed comparable TxB2 levels with those of control. CONCLUSION: The Pall BB25 filter efficiently protected the guinea pigs from sensitization to NRL. This filter can be used as a complementary measure for avoidance of NRL contact during surgical procedures particularly if the mechanical ventilator apparatus contain NRL devices.

The immune response to a schistosomacide, amoscanate. II. Cell-mediated immune responses.

A potent antischistosomal drug, Amoscanate, was found to induce vigorous serum antibody responses when either fed or administered parenterally as a drug-protein conjugate. Because of preliminary evidence that the drug could bind covalently to proteins in vivo, we decided to investigate the possibility that the drug could act as a contact sensitizing agent like DNCB. It was found that Amoscanate could induce a delayed-type hypersensitivity (DTH) response when painted on the shaved skin of guinea pigs. Moreover, the type of DTH response elicited was found to be cutaneous basophilic hypersensitivity (CBH). The significance of these findings are discussed.

Gut mucosal mast cells and goblet cells during acute graft-versus-host disease in rats.

Intestinal inflammation occurs in both nematode infections and graft-versus-host disease (GVHD). In nematode infections, this involves the proliferation of mucosal mast cells (MMC) and goblet cells (GC). To examine MMC and GC responses in GVHD, female Lewis rats were given allogeneic bone marrow (BM). Each animal received 1,020 rads and, one day later, 6 X 10(7) ACI BM cells plus 2 X 10(7) ACI spleen cells i.v. Control rats received 6 X 10(7) BM cells. On days 4, 8, 12, 16 and 20 post-transplant, rats were sacrificed and their intestines removed and prepared for histological examination of MMC and GC. Cells in 10 villus-crypt units (VCU) of the gut were counted for each animal. Skin and tongue were also removed and examined to determine the degree of GVHD. GVHD was first evident on day 8 in allogeneic BM recipients and progressed thereafter. No evidence of GVHD was seen in syngeneic BM recipients. Rats receiving allogeneic BM showed a 10-fold increase from day 12 to day 20 (p less than 0.01). Rats receiving syngeneic BM showed no significant change in MMC through the 20th day. In animals with GVHD, GC decreased by day 12 and remained lower than control animals during the subsequent 8 days. It was concluded that, similar to nematode infection, MMC proliferation is a feature of GVHD. In contrast, GC do not appear to proliferate in an acute GVHD.