Effects of maternal antibodies on protection and development of antibody responses to human rotavirus in gnotobiotic pigs

Although maternal antibodies can protect against infectious disease in infancy, they can also suppress active immune responses. The effects of circulating maternal antibodies, with and without colostrum and milk antibodies, on passive protection and active immunity to human rotavirus (HRV) were examined in gnotobiotic pigs. Pigs received intraperitoneal injections of high-titer serum (immune pigs [groups 1 and 2]) from immunized sows, low-titer serum from naturally infected sows (control pigs [groups 3 and 4]), or no serum (group 5). Immune or control colostrum and milk were added to the diet of groups 2 and 4, respectively. After inoculation (3 to 5 days of age) and challenge (postinoculation day [PID] 21) with virulent HRV, the effects of maternal antibodies on protection (from diarrhea and virus shedding), and on active antibody responses (measured by quantitation of antibody-secreting cells [ASC] in intestinal and systemic lymphoid tissues by ELISPOT) were evaluated. Groups 1 and 2 had significantly less diarrhea and virus shedding after inoculation but higher rates of diarrhea and virus shedding after challenge than did groups 3 and 5. Group 1 and 2 pigs had significantly fewer immunoglobulin A (IgA) ASC in intestinal tissues at PID 21 and at postchallenge day (PCD) 7 compared to group 5. Significantly fewer IgG ASC were present in the intestines of group 2 pigs at PID 21 and PCD 7 compared to group 5. There was a trend towards fewer ASC in intestinal tissues of group 2 than group 1, from PID 21 on, with significantly fewer IgA ASC at PCD 7. IgG ASC in the duodenum and mesenteric lymph nodes of group 3 and 4 pigs were significantly fewer than in group 5 at PCD 7. These decreases in ASC emphasize the role of passive antibodies in impairing induction of ASC rather than in merely suppressing the function of differentiated B cells. To be successful, vaccines intended for populations with high titers of maternal antibodies (infants in developing countries) may require higher titers of virus, multiple doses, or improved delivery systems, such as the use of microencapsulation or immune stimulating complexes, to overcome the suppressive effects of maternal antibodies.     

Antisaccade task performance in questionnaire-identified schizotypes

Individuals who scored high on Perceptual Aberration-Magical Ideation Scales (Per-Mag; n = 90), the Social Anhedonia Scale (SocAnh; n = 39), and control participants (n = 89) were administered saccadic refixation (prosaccade) and saccadic suppression (antisaccade) tasks. Eye movements were scored in terms of error rates and latency. None of the groups differed in terms of their performance on the prosaccade task. Both the Per-Mag (p < 0.01) and SocAnh (p < 0.05) groups exceeded the controls in terms of mean antisaccade errors. The high-risk groups did not differ from each other. Eighteen of the Per-Mag individuals and 10 of the SocAnh individuals displayed deviant antisaccade performance. These findings are particularly interesting in light of suggestive evidence that antisaccade task deficits may serve as a marker of susceptibility to schizophrenia. It is hypothesized that the individuals who scored aberrantly on the Chapman scales and displayed antisaccade performance deficits are most likely to be at risk for the development of psychosis.     

Ovine arylalkylamine N-acetyltransferase in the pineal and pituitary glands: differences in function and regulation

The enzyme arylalkylamine N-acetyltransferase (AANAT; EC 2.3.1.87) has been conventionally linked with the biosynthesis of melatonin within the pineal gland and retina. This study establishes that AANAT messenger RNA (mRNA) and functional enzyme occurs within the pars tuberalis (PT) and to a lesser degree within the pars distalis (PD) of the sheep pituitary gland; expression in these tissues is approximately 1/15th (PT) and 1/300th (PD) of that in the ovine pineal gland. AANAT mRNA in the PT appears to be expressed in the same cells as the Mel1a receptor. No evidence was obtained to indicate that either PT or PD cells have the ability to synthesize melatonin, suggesting that this enzyme plays a different functional role in the pituitary. We also found that cAMP regulation of the abundance of AANAT mRNA differs between the PT and pineal gland. Forskolin (10 microM) has no effect on pineal AANAT mRNA levels, yet represses expression in the PT. This suppressive influence could be mediated by ICER (inducible cAMP response early repressor), which is induced by forskolin in both tissues. Although it appears that the specific function and regulation of AANAT in the pituitary gland differ from that in the pineal gland, it seems likely that AANAT may play a role in the broader area of signal transduction through the biotransformation of amines.     

Genitourinary anomalies in the CHARGE association

PURPOSE: We identified the incidence and types of genital and urinary anomalies, and established a plan for evaluating the urinary system in the CHARGE association. MATERIALS AND METHODS: We retrospectively reviewed the charts of 32 patients in whom the CHARGE association was diagnosed. RESULTS: Of the 32 patients identified 22 (69%) had genitourinary abnormalities. Genital anomalies, including micropenis, penile agenesis, hypospadias, chordee, cryptorchidism, a bifid scrotum, atresia of the uterus, cervix and vagina, and hypoplastic labia majora, labia minora and clitoris, were present in 18 patients (56%). Of the 24 patients who underwent renal ultrasound 10 (42%) were diagnosed with urinary tract anomalies including a solitary kidney, hydronephrosis, renal hypoplasia and duplex kidneys. Further evaluation revealed vesicoureteral reflux, neurogenic bladder secondary to spinal dysraphism, nephrolithiasis, ureteropelvic junction obstruction and a nonfunctioning upper pole in both duplex kidneys. CONCLUSIONS: There is a high incidence of genitourinary anomalies in the CHARGE association. Because of this high incidence of anomalies, patients with this condition should undergo a careful genitourinary evaluation, including renal and bladder ultrasound, and voiding cystourethrography screening.     

Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia

PURPOSE: To assess the effectiveness and safety of self-expanding metallic stents as a primary palliative treatment for inoperable malignant colorectal strictures. METHODS: Under radiological guidance 20 self-expanding metallic Wallstents were implanted in 16 consecutive patients with colorectal stenoses caused by malignant neoplasms, when surgical treatment of the condition had been ruled out. The patients were followed up clinically for 1-44 months, until death or termination of this study. RESULTS: The stents were successfully implanted in all cases and resolved the clinical obstruction in all the patients except one, who underwent subsequent colostomy. During follow-up of the remaining 15 patients, clinical complications arising from the procedure were pain (two patients), minor rectal bleeding (one patient), and severe rectal bleeding (one patient) (26%). There were three cases of stent migration and three cases of stent occlusion, and reintervention by us was necessary in 20% of cases (3/15). The mean life span following the procedure was 130 days, and none of the patients exhibited clinical symptoms of obstruction at the time of death (12 patients) or termination of the study (3 patients). CONCLUSION: Deployment of metallic stents under radiologic guidance is an effective alternative as a primary palliative measure in malignant colorectal obstruction, though the possible clinical complications and need for repeat intervention during follow-up should be taken into account.     

Grafting of enzymes on collagen films using Woodward's reagent "K" and a water-soluble carbodiimide derivative

Two new methods of activation were developed to graft enzymes on collegen films. They involved chemical modifications of surface groups of collagen either by Woodward's reagent "K" or by EDC, a water-soluble derivative of carbodiimide. EDC was a better coupling agent and a detailed study was conducted with this agent. It could be used either in a global method of activation and coupling, or in a two-step procedure of activation of collagen, followed by spontaneous coupling of enzyme. All enzymes tested were successfully bound: malate dehydrogenase, lactate dehydrogenase, aspartate aminotransferase, urease, creatine kinase, hexokinase. The influence on the yield of grafted enzyme, of pretreatment of films, time and temperature of EDC activation, concentration of EDC and enzyme, protecting agents was studied. Stability of enzyme activity on storage was greatly increased after grafting. A co-grafted dual system creatine kinase/heoxkinase, was achieved which exhibited a good efficiency. A striking renaturing process at 0-4degreesC after thermal denaturation, was observed with hexokinase.     

The use of imaging studies in the diagnosis and management of thyroid cancer and hyperparathyroidism

With the variety of radiopharmaceutical agents and refined imaging techniques, thyroid and parathyroid imaging provides much valuable clinical information. The use of imaging is most important in the follow-up of differentiated (DTC) and medullary thyroid cancer (MTC). Patients with DTC are followed with serum thyroidglobulin and 131I whole body scintigraphy when the serum thyroglobulin level is elevated. When the 131I scintigram is negative, 201Tl scintigraphy may best identify the site of recurrent DTC. Alternative radioisotopes, ultrasound, CT, and FDG PET are also useful in localizing the site of DTC metastases. MTC recurrences and metastases are more difficult to image. Selective venous catheterization is the most sensitive and specific method for detecting areas of recurrent MTC. High-resolution ultrasound, CT, MR imaging, and scintigraphy are all capable of, and useful in, detecting macroscopic foci of metastatic tumor. Somatostatin receptor scintigraphy and 99mTc DMSA have been the most frequently used nuclear imaging agents in patients with recurrent MTC. Imaging for hyperparathyroidism remains controversial. Sestambi has become the preferred isotope for parathyroid scintigraphy; whereas high-resolution ultrasound is also frequently used. Preoperative imaging is being used as a method to allow a unilateral neck exploration, more recently, in conjunction with intraoperative 1-84 PTH assay and with intraoperative use of the gamma probe. Most often, parathyroid imaging is performed before reoperation for persistent hyperparathyroidism.     

Delayed onset of hand tremor related to cerebellar hemorrhage

Spontaneous hematomas are rare and can present with acute or chronic symptoms. Our patient presented with deep vein thrombosis of the lower extremity associated with a spontaneous pelvic hematoma. This lesion was radiologically and clinically indistinguishable from a soft-tissue neoplasm. The case of a spontaneous pelvic neoplasm in an otherwise healthy young man is presented and the literature reviewed regarding issues of differential diagnosis and clinical management.     

Medication adherence in rheumatoid arthritis patients: older is wiser

OBJECTIVES: To create a profile of individuals nonadherent to their medications in an age-stratified sample (ages 34-84) of community-dwelling rheumatoid arthritis patients. The relative contributions of age, cognitive function, disability, emotional state, lifestyle, and beliefs about illness to nonadherence were assessed. DESIGN: A direct observation approach was used in conjunction with structural equation modeling. All participants were administered a preliminary assessment battery. Medications were then transferred to vials with microelectronic caps that recorded medication events for all medications for the next 4 weeks. PARTICIPANTS AND SETTING: A volunteer sample of 121 community-dwelling rheumatoid arthritis (RA) patients were recruited from newspaper ads, posters, and via informal physician contact from private rheumatology practices in Atlanta and Athens, Georgia. Written verification of the RA diagnosis and a disease severity rating were obtained from personal physicians before patients were enrolled in the study. Patients were tested in a private physician's office, and their medication adherence was monitored electronically for a month in their every-day work and home settings. MEASUREMENTS AND RESULTS: Structural equation modeling techniques were used to develop a model of adherence behavior. Cognitive and psychosocial measures were used to construct latent variables to predict adherence errors. The model of medication adherence explained 39% of the variance in adherence errors. The model demonstrated that older adults made the fewest adherence errors, and middle-aged adults made the most. A busy lifestyle, age, and cognitive deficits predicted nonadherence, whereas coping with arthritis-related moods predicted adherence. Illness severity, medication load, and physical function did not predict adherence errors. Omission of medication accounted for nearly all errors. CONCLUSION: Despite strong evidence for normal, age-related cognitive decline in this sample, older adults had sufficient cognitive function to manage medications. A busy lifestyle and middle age were more determinant of who was at risk of nonadherence than beliefs about medication or illness. Thus, practicing physicians should not assume that older adults have insufficient cognitive resources to manage medications and that they will be the most likely to make adherence errors. Very busy middle-aged adults seem to be at the greatest risk of managing medications improperly.