Endogenous opioid tone in patients with rheumatoid arthritis

A monoclonal antibody giving a dominant reaction with the group-specific polysaccharide of streptococcus group B in an ELISA test has been developed. The purified polysaccharide exhibited a high positivity with reference anti B streptococcal antiserum in the ELISA test. Cross-tests of antibodies with other groups of streptococci provided a minimum cross-reaction only in the case of G streptococci. Monoclonal antibodies were prepared using Streptococcus agalactiae S 589 MT strain isolated from a case of bovine mastitis which does not express Ia, Ib, II, III, IV and V type antigens, nor C, R and X protein antigens.     

Conjugate imagery in the automated reproduction of three dimensional coordinates from two dimensional coordinate data

The three-dimensional video analysis of human motion commonly utilises automated image processing and digitisation processes to produce real-time unidentified two-dimensional coordinate data of segmental markers. In what can be a time-consuming process the two-dimensional data are then identified and tracked to produce three-dimensional coordinates. This paper presents an approach to the automated reproduction of three-dimensional coordinates from two-dimensional coordinates data. Conjugate imaging techniques were utilised in the development of four criterion measures for determining the validity of conjugate (corresponding) image points. An algorithm based on the criterion measures was then developed for the automated reproduction of three dimensional coordinates from camera image coordinate data. The algorithm was tested with a 55 point marker system viewed in four video cameras (digitisation error approx. 0.2%, lab point separation > or = 6 cm). The success of the algorithm was dependent on the closeness of markers, the accuracy of the photogrammetric system, and the number of markers visible in two camera images. The present research has developed techniques based on conjugate imagery for the automated reproduction of three-dimensional coordinates from two-dimensional data, and provided a bases for further development of automated three-dimensional tracking.     

Selective metabotropic receptor agonists distinguish non-ionotropic glutamate binding sites

Metabotropic glutamate receptors (mGluRs) are thought to mediate diverse processes in brain including synaptic plasticity and excitotoxicity. These receptors are often divided into three groups by their pharmacological profiles. [3H]Glutamate binding in the presence of compounds selective for ionotropic glutamate receptors can be used as a general assay for these receptors; subtypes of this non-ionotropic [3H]glutamate binding differ in both pharmacology and anatomical distribution, and are differentially sensitive to quisqualate. The characteristics of these binding sites are consistent with those of group 1 (high-affinity quisqualate) and group 2 (low-affinity quisqualate) mGluRs. Under our assay conditions, no [3H]glutamate binding to group 3-like (L-AP4 sensitive) sites could be demonstrated. We have attempted to characterize particular agents which may selectively measure [3H]glutamate binding to mGluR subtypes. We used two isomers of 2-(carboxycyclopropyl)glycine, L-CCG-I and L-CCG-II, and the (2S,1'R,2'R,3'R) isomer of 2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) as competitors of non-ionotropic [3H]glutamate binding sites. DCG-IV clearly distinguishes two binding sites. Quantitative levels of DCG-IV binding by anatomic region correlate with quisqualate-defined binding subtypes: high-affinity DCG-IV binding correlates with low-affinity quisqualate binding, whereas low-affinity DCG-IV binding correlates with high-affinity quisqualate binding. L-CCG-II displaces only one type of non-ionotropic [3H]glutamate binding, corresponding to high-affinity quisqualate binding. Therefore DCG-IV and L-CCG-II at appropriate concentrations appear to distinguish binding to putative group 2 vs. group 1 mGluRs. L-CCG-I displaces both high- and low-affinity quisqualate binding sites, but unlike the other two compounds, does not clearly distinguish between them.     

Overview of the epidemiology of colorectal cancer

The surgical treatment for strabismus in infants generally results in microtropia or subnormal binocular vision. Although the clinical characteristics of these conditions are well established, there are important questions about the mechanisms of binocular vision in these patients that can best be investigated in an appropriate animal model. In the present psychophysical investigations, spatial frequency response functions for disparity-induced fusional vergence and for local stereopsis were studied in macaque monkeys, who demonstrated many of the major visual characteristics of patients whose eyes were surgically aligned during infancy. In six rhesus monkeys, unilateral esotropia was surgically induced at various ages (30-184 days of age). However, over the next 12 months, all of the monkeys recovered normal eye alignment. Behavioral measurements at 4-6 years of age showed that the monkeys' prism-induced fusional vergence responses were indistinguishable from those of control monkeys or humans with normal binocular vision. Investigations of stereo-depth discrimination demonstrated that each of the experimental monkeys also had stereoscopic vision, but their stereoacuities varied from being essentially normal to severely stereo-deficient. The degree of stereo-deficiency was not related to the age at which surgical esotropia was induced, or to the presence or absence of amblyopia, and was not dependent on the spatial frequency of the test stimulus. Altogether, these experiments demonstrate that a temporary, early esotropia can affect the binocular disparity responses of motor and sensory components of binocular vision differently, probably because of different sensitive periods of development for the two components.     

The impact of beta-receptor blocker addition to high-dose angiotensin-converting enzyme inhibitor-nitrate therapy in heart failure

BACKGROUND: The natural history of heart failure is one of continued worsening of cardiac function. Beta-receptor blocker therapy has been effective in improving clinical status and left ventricular function in patients with heart failure. Similarly, high doses of angiotensin-converting enzyme (ACE) inhibitors with nitrates partially reverse the ventricular remodeling of heart failure. HYPOTHESIS: We tested the hypothesis that beta-blocker therapy added to high-dose ACE inhibitor-nitrates would potentiate the reversal of heart failure. METHODS: Thirteen patients, aged 52 +/- 8 years, with moderate to severe heart failure, 12 of whom were referred for transplant consideration, with heart failure duration of 4.8 +/- 2.2 years, were prospectively followed for 12 months. Baseline echocardiographic ejection fraction was 19 +/- 8%, and presenting New York Heart Association class was 2.9 +/- 0.7. Angiotensin-converting enzyme inhibitors and nitrates were uptitrated over 6 months to a final dose of lisinopril 53 +/- 31 mg/day, and isosorbide dinitrate 217 +/- 213 mg/day. At 6 months, beta-blocker therapy with atenolol was initiated and titrated to a final dose of 46 +/- 23 mg/day. Two-dimensional Doppler echocardiography and metabolic stress testing were performed at baseline, at 6 months on lisinopril-nitrates only, and at 12 months on combined ACE inhibitor-nitrate and beta-blocker therapy. RESULTS: New York Heart Association classification improved from 2.9 +/- 0.7 to 1.8 +/- 0.8 on lisinopril-nitrates (p < 0.05), and to 1.5 +/- 0.5 with the addition of beta blockade (p = NS). On follow-up, peak oxygen consumption rose from 17 +/- 7 ml O2/kg/min at baseline to 21 +/- 5 ml O2/kg/min at 6 months on lisinopril-nitrates (p = 0.06) without further change on beta blockade. Ejection fraction rose from 19 +/- 8 to 33 +/- 14% on lisinopril-nitrates at 6 months (p = 0.005) and to 36 +/- 18% on beta blockade at 12 months (p = NS). CONCLUSION: High-dose ACE inhibitor-nitrate therapy significantly improved patient clinical status and left ventricular systolic function in heart failure. The addition of beta-receptor blockade over and above high-dose ACE inhibitor-nitrates was well tolerated but had no further impact on symptomatic status, exercise tolerance, or left ventricular systolic function. The potential for pharmacologic reversal of heart failure remodeling may be finite despite the use of complementary therapies. Larger placebo-controlled and randomized trials of beta-receptor blockade added to high-dose ACE inhibitor-nitrate therapy are needed to confirm these observations.     

4-Alkylpiperidines related to SR-48968: potent antagonists of the neurokinin-2 (NK2) receptor

A series of 4-alkylpiperidine derivatives related to the potent neurokinin-2 (NK2) receptor antagonist SR-48968 (1) is described. Simple aliphatic derivatives were found to be poorly active, but appropriate placement of an alcohol functional group afforded compounds that were of similar activity to 1. Several representatives in this series, such as the 4-(1-hydroxy-1-ethylpropyl)piperidine (14), were found to exhibit oral activity in a model of labored abdominal breathing in guinea pigs. These results expand the latitude of substituents available in this region of this series of NK2 receptor antagonists.     

Correlation of cecal microflora of HLA-B27 transgenic rats with inflammatory bowel disease

Transgenic rats with a high level of expression of the human major histocompatibility complex class I molecule HLA-B27 develop chronic inflammatory bowel disease (IBD) and arthritis. Assessment of the cecal microflora showed a rise in numbers of Escherichia coli and Enterococcus spp., corresponding to the presence and severity of IBD in these rats.     

Regulation of cytochrome P450 enzymes by aryl hydrocarbon receptor in human cells: CYP1A2 expression in the LS180 colon carcinoma cell line after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3-methylcholanthrene

The Food Research and Action Center estimates that approximately 12% of all families with children younger than 12 years old experience food insufficiency in the United States. The authors conducted 16 focus groups with 141 participants, who were either at risk or experienced food insufficiency, to learn about coping strategies. Individual and network-level coping mechanisms were used to manage insufficient food supply. Social networks included family, friends, and neighbors. The assistance provided included food aid, information, and emotional support. Not all networks were relied on or accessed by everyone. Most participants reported that they relied on family members first, followed by friends, and then neighbors. Parents found reliance on anyone as stressful and often threatening. In conclusion, as the social welfare system becomes constrained, more and more households may experience food insufficiency. Responsive policies are therefore needed to assist low-income families.     

Optimization of evening insulin dose in patients using the short-acting insulin analog lispro

OBJECTIVE: A three-way, crossover, open-label, randomized study was designed to compare the evening and night (1800-0800) glycemic control when the evening premeal lispro dose was reduced by 20% and the bedtime basal NPH dose increased by 25%, or when the basal NPH dose was moved to before dinner at 1800, compared with the control arm on standard premeal human regular insulin and pre-bedtime NPH insulin. RESEARCH DESIGN AND METHODS: A total of 13 type 1 diabetic patients who use a premeal plus basal insulin regimen were studied on three separate days, with identical meals and snacks at the same times on each study day. On the control study day, patients received human regular insulin before dinner and NPH at bedtime in their usual doses. On another day, lispro was given before dinner with a dose reduction of 20%, and NPH at bedtime at 125% of usual dose. In the third regimen, the lispro and NPH were administered together in their usual dose before the evening meal by separate injections. The three regimens were tested in random order. RESULTS: Postprandial (1800-2200) blood glucose concentrations were lower after reduced-dose lispro compared with human regular insulin (6.0 +/- 0.3 [SEM] vs. 7.4 +/- 0.3 mmol/l, P < 0.05). Nighttime (2400-0400) blood glucose concentrations were not different (8.6 +/- 0.3 vs. 9.2 +/- 0.3 mmol/l, NS), and prebreakfast concentrations were also unchanged (7.7 +/- 0.9 vs. 8.7 +/- 0.8 mmol/l) after lispro with increased-dose NPH compared with standard insulin. By contrast, both nighttime (10.0 +/- 0.3 mmol/l, P < 0.05) and fasting glucose concentrations (10.8 +/- 0.6 mmol/l, P < 0.05) were significantly higher with dinnertime usual-dose lispro plus dinnertime usual-dose NPH compared with standard human insulin. Hypoglycemia at night (blood glucose < 3.0 mmol/l) did not differ between study days, but it was more frequent postprandially after dinner usual-dose lispro plus early NPH (2 vs. 7 patients, P = 0.062). CONCLUSIONS: With lower mealtime and higher basal bedtime insulin doses, patients using insulin lispro may be able to gain an overall improvement in evening blood glucose control without deteriorated nighttime glucose levels. Earlier basal NPH dosage alone does not ameliorate the nighttime hyperglycemia of short-acting insulin analog regimens.