The latency of the cat vestibulo-ocular reflex before and after short- and long-term adaptation

Latencies of normal and adapted feline vestibulo-ocular reflex (VOR) were studied in five cats by applying ± 20°/s horizontal head velocity steps (4000°/s₂ acceleration) and measuring the elicited horizontal or vertical reflex eye responses. Normal VOR latency was 13.0 ms ± 1.9 SD. Short-term adaptation was then accomplished by using 2 h of paired horizontal sinusoidal vestibular stimulation and phase-synchronized vertical optokinetic stimulation (cross-axis adaptation). For long-term adaptation, cats wore ×0.25 or ×2.2 magnifying lenses for 4 days. The cats were passively rotated for 2 h/day and allowed to walk freely in the laboratory or their cages for the remainder of the time. The latency of the early (primary) adaptive response was 15.2ms±5.2 SD for crossaxis adaptation and 12.5 ms±3.9 SD for lens adaptation. This short-latency response appeared within 30 min after beginning the adaptation procedure and diminished in magnitude overnight. A late (secondary) adaptive response with latency of 76.8 ms±7.0 SD for cross-axis adaptation and 68.1 ms±8.8 SD for lens adaptation appeared after approximately 2 h of adaptation. It had a more gradual increase in magnitude than the primary response and did not diminish in magnitude overnight. These data suggest that brainstem VOR pathways are a site of learning for adaptive VOR modification, since the primary latency is short and has a similar latency to that of the normal VOR.     

Progress in Rhesus Histocompatibility Typing Resulting from the Second International Nonhuman Primate Histocompatibility Workshop (1973)

The Second International Nonhuman Primate Histocompatibility Workshop permitted comparison of rhesus monkey alloantisera developd in various laboratories on a single common panel of related and unrelated monkeys. Analysis of the data permits the conclusion that at least nine specificities are recognized by more than one laboratory, including six at the first locus and three at the second locus.     

The effects of diazoxide on total lung resistance in the anesthetized paralyzed guinea-pig

The initial effects of diazoxide on dynamic pulmonary compliance (C_L) and flow resistance (R_L) were measured in paralyzed, anesthetized guinea-pigs. Diazoxide (10, 20 or 40 mg/kg) caused a dose-related increase in R_L and decrease in C_L. The increase in R_L could be selectively abolished by glossopharyngealotomy or decentralization, and by pretreatment with mepyramine (0.1 mg/kg) or disodium cromoglycate (10 mg/kg). Pretreatment with indomethacin (0.1 mg/kg) or acetylsalicylic acid (1 mg/kg) selectively eliminated the decreases in compliance observed after diazoxide. It is concluded that diazoxide initially constricts both large (R_L) and small (C_L) airways. The constriction of the large airways may involve a release of histamine, whereas the constriction of the small airways may be mediated by a prostaglandin or prostaglandin-like substance.     

Patient and partner perceptions about preventing genital herpes transmission

Research over the past decade has provided a new understanding of genital herpes transmission and measures that can reduce transmission risk. It is unclear, however, how those affected by genital herpes access and interpret this information to make decisions about risk behaviours. This study measured how people with genital herpes and their partners perceived prevention methods, barriers and facilitating factors, and information sources. Formative evaluation was conducted, and survey data were collected from visitors to four websites (n=1849). Results suggest that the prevention messages of refraining from sex during disease outbreaks and condom use have had the greatest reach. Misconceptions about the potential role of suppressive antiviral therapy for genital herpes prevention persist among a substantial percentage of respondents. Accurate information concerning transmission between outbreaks, the effectiveness of condoms and the role of antiviral medication is critical in preventing the spread of genital herpes.     

Effect of hemoglobin concentration variation on the accuracy and precision of glucose analysis using tissue modulated, noninvasive, in vivo Raman spectroscopy of human blood: a small clinical study

Tissue modulated Raman spectroscopy was used noninvasively to measure blood glucose concentration in people with type I and type II diabetes with HemoCue fingerstick measurements being used as reference. Including all of the 49 measurements, a Clarke error grid analysis of the noninvasive measurements showed that 72% were A range, i.e., clinically accurate, 20% were B range, i.e., clinically benign, with the remaining 8% of measurements being essentially erroneous, i.e., C, D, or E range. Rejection of 11 outliers gave a correlation coefficient of 0.80, a standard deviation of 22 mg/dL with p<0.0001 for N=38 and places all but one of the measurements in the A and B ranges. The distribution of deviations of the noninvasive glucose measurements from the fingerstick glucose measurements is consistent with the suggestion that there are at least two systematic components in addition to the random noise associated with shot noise, charge coupled device spiking, and human factors. One component is consistent with the known variation of fingerstick glucose concentration measurements from laboratory reference measurements made using plasma or whole blood. A weak but significant correlation between the deviations of noninvasive measurements from fingerstick glucose measurements and the test subject's hemoglobin concentration was also observed.     

Relationship between adherence to inhaled corticosteroids and poor outcomes among adults with asthma

BACKGROUND: Regular use of inhaled corticosteroids (ICSs) can improve asthma symptoms and prevent exacerbations. However, overall adherence is poor among patients with asthma. Objective To estimate the proportion of poor asthma-related outcomes attributable to ICS nonadherence. METHODS: We retrospectively identified 405 adults age 18 to 50 years who had asthma and were members of a large health maintenance organization in southeast Michigan between January 1, 1999, and December 31, 2001. Adherence indices were calculated by using medical records and pharmacy claims. The main outcomes were the number of asthma-related outpatient visits, emergency department visits, and hospitalizations, as well as the frequency of oral steroid use. RESULTS: Overall adherence to ICS was approximately 50%. Adherence to ICS was significantly and negatively correlated with the number of emergency department visits (correlation coefficient [ R ] = -0.159), the number of fills of an oral steroid ( R = -0.179), and the total days' supply of oral steroid ( R = -0.154). After adjusting for potential confounders, including the prescribed amount of ICS, each 25% increase in the proportion of time without ICS medication resulted in a doubling of the rate of asthma-related hospitalization (relative rate, 2.01; 95% CI, 1.06-3.79). During the study period, there were 80 asthma-related hospitalizations; an estimated 32 hospitalizations would have occurred were there no gaps in medication use (60% reduction). CONCLUSIONS: Adherence to ICS is poor among adult patients with asthma and is correlated with several poor asthma-related outcomes. Less than perfect adherence to ICS appears to account for the majority of asthma-related hospitalizations.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Typing of clinical herpes simplex virus isolates with mouse monoclonal antibodies to herpes simplex virus types 1 and 2: comparison with type-specific rabbit antisera and restriction endonuclease analysis of viral DNA

A total of 122 clinical isolates of herpes simplex virus (HSV) from 107 patients were typed by using an indirect immunoperoxidase technique with commercially available type-specific rabbit antisera, recently developed mouse monoclonal antibodies to HSV types 1 and 2, and restriction endonuclease analysis of viral DNA. With the commercially available type-specific rabbit antisera, 34% of clinical HSV isolates were of indeterminate type; 63% of them were typed as HSV type 1 and 37% as HSV type 2 by using monoclonal antibody and restriction enzyme typing systems. Typing by immunofluorescence assay with the monoclonal antibodies gave identical results to those obtained by restriction enzyme analysis. Simultaneous infection with both HSV types was demonstrated by monoclonal antibody typing in five isolates from three patients. These findings were subsequently confirmed by plaque purification and restriction endonuclease analysis of viral DNA. Monoclonal antibodies were as sensitive as restriction enzyme analysis for the typing of clinical HSV isolates. Because of their simplicity, they are more amenable to use in clinical laboratories than is restriction endonuclease analysis.     

The Gm-Pi linkage heterogeneity in view of Pi M subtypes

In this study linkage between the loci for Gm (γ-type heavy-chain immunoglobulin markers) and Pi (α₁-antitrypsin/α₁-protease inhibitor) has been shown in families segregating for the Pi M subtypes (Ml, M2, M3 and Msal) as identified by separator isoelectric focusing. The estimate for the Gm-Pi (M-type) recombination is 0-29 (95% limits 0-24-O37) at a peak lod score of 4-31 and with no sex difference. This value is not significantly different from updated recombination frequency estimates for Gm-Pi in Pi MS (0-26) and Pi MZ, SZ and FZ families (0 21). The overall Gm-Pi recombination fraction estimate of 0 26 (95 % limits O23-0-30) at a peak lod score of 20-75 must now be considered as solid. There is a significant heterogeneity within the male Pi MZ families in that the new Finnish families show a higher recombination between Gm and Pi. There is also a possible segregation distortion (Z:M = 23:8). The heterogeneity is discussed in terms of haplotypes, the behaviour of which could be determined by linked genes or chromosomal rearrangements. The possibility that the α₁-antitrypsin level influences recombination frequency has not been ruled out, but cannot explain the heterogeneity within Pi MZ families.     

Localization of the third component of complement on the cell wall of encapsulated Staphylococcus aureus M: implications for the mechanism of resistance to phagocytosis.

Encapsulated Staphylococcus aureus strains are more virulent than unencapsulated staphylococci, and this phenomenon has been associated with decreased opsonization of encapsulated bacteria by normal human serum. Peptidoglycan, a major cell wall component of S. aureus, has been shown to promote opsonization of this bacterial species by certain components of the serum complement system. However, when the processes of complement activation and opsonization of encapsulated staphylococci have been studied, it has been found that encapsulated bacteria activate complement efficiently and C3 is bacteria associated, yet these organisms are not efficiently phagocytized by human polymorphonuclear leukocytes. In this study, the hypothesis was tested that opsonically active molecules are not on the true external surface of encapsulated organisms but rather are cell wall associated and thus "hidden" from human polymorphonuclear leukocytes. By using immunoelectronmicroscopy, C3 was found to be localized on the cell wall of an encapsulated S. aureus strain after incubation of the organism in normal human serum. When shrinkage of the capsule was prevented by treatment with anticapsular antibody, the C3 was again shown to be cell wall associated and located beneath the bacterial capsule. These results suggest that encapsulated S. aureus may resist phagocytosis because opsonically active C3 molecules are not exposed at the true external surface of the bacterium.