HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.     

The course of geriatric depression with "reversible dementia": a controlled study

OBJECTIVE: The goals of this longitudinal investigation were 1) to study the rate of development of irreversible dementia in elderly depressed patients with a dementia syndrome that subsided after improvement of depression and 2) to compare it with that of depressed, never-demented patients. METHOD: The subjects were 57 elderly patients consecutively hospitalized for major depression. At entry into the study, 23 subjects also met criteria for "reversible dementia," while 34 were without dementia. After a systematic clinical evaluation, the subjects were followed up at approximately yearly intervals for an average of 33.8 months. RESULTS: Irreversible dementia developed significantly more frequently in the depressed group with reversible dementia (43%) than in the group with depression alone (12%). Survival analysis showed that the group with reversible dementia had a 4.69-times higher chance of having developed dementia at follow-up than the patients with depression alone. No clinical characteristics at entry into the study were found to discriminate the subjects who developed irreversible dementia during the follow-up period from those who remained nondemented. CONCLUSIONS: These findings suggest that geriatric depression with reversible dementia is a clinical entity that includes a group of patients with early-stage dementing disorders. Therefore, identification of a reversible dementia syndrome is an indication for a thorough diagnostic workup and frequent follow-ups in order to identify treatable neurological disorders.     

Plasma somatomedin activity in normal and scoliotic children

In a study of plasma somatomedin activity in childhood scoliosis a group of five patients with congenital scoliosis was found to have significantly lower plasma somatomedin levels compared with a group of 20 normal children. A group of 52 patients with "idiopathic" scoliosis had normal plasma somatomedin levels. There is no apparent difference in the plasma somatomedin activity between the sexes, and no change in plasma somatomedin activity with chronologic age in these children, suggesting that normal adult somatomedin levels have been reached.     

Applications of 'TissueQuant'- a color intensity quantification tool for medical research

This paper demonstrates the use of TissueQuant - an image analysis tool for quantification of color intensities which was developed for use in medical research where the stained biological specimen such as tissue or antigen needs to be quantified. TissueQuant provides facilities for user interaction to choose and quantify the color of interest and its shades. Gaussian weighting functions are used to provide a color score which quantifies how close the shade is to the user specified reference color. We describe two studies in medical research which use TissueQuant for quantification. The first study evaluated the effect of petroleum-ether extract of Cissus quadrangularis (CQ) on osteoporotic rats. It was found that the analysis results correlated well with the manual evaluation, p < 0.001. The second study evaluated the nerve morphometry and it was found that the adipose and non adipose tissue content was maximum in radial nerve among the five nerves studied.     

Infections due to Lancefield group F and related Streptococci (S. milleri, S. anginosus)

We can no longer accept classification of streptococci solely on the basis of hemolytic reactions or Lancefield agglutinations. While the "viridans" streptococci cannot be serologically differentiated, physiological separation of the species offers a satisfactory method of classifying human isolates. We review the microbiology of Lancefield group F and related streptococci (S. milleri, S. anginosus), emphasizing microbial ecology and current taxonomic considerations. A series of 28 patients infected with these organisms is presented. There was a striking male predominance in the series (6:1) as well as an obvious association with underlying diseases and/or antecedent trauma. The most remarkable feature of these pathogens is their predilection for abscess formation, confirming their overdue recognition as the most common "viridans" streptococcus recovered from abscesses within internal organs. We observed purulent disease of the nervous and skeletal systems, oral cavity, lung and pleural space, abdomen and subcutaneous tissues. Microbial synergy (i.e. polymicrobic infection) was not a requisite for abscess formation. Four of the five deaths in this series occurred in patients 60 years of age of older. Some degree of variability in antimicrobial susceptibility was noted, so speciation alone may not always provide sufficient information on which to base a therapeutic decision.     

Psychophysiological studies in the pre-school children

The behavior of 24 children, aged 3-6 years, was recorded on video-tape. Simultaneously the ECG was recorded telemetrically. These observations were made during two pre-school educational programs lasting 90 minutes each: "Didactic games" and "Elementary music and movement program". For each child a scale was developed to show the correlation of mean heart-rate and well defined motor-activity. It was evident that the mean heart-rate was higher during the music program than during the didactic program, corresponding to the higher motor-activity. But it was found that in the didactic program the variation of the heart-rate within short intervals was higher due to the more frequent occurrence of respiratory arrhythmias. It was also seen that during the music program the children showed no signs of exertion as they did towards the end of the didactic program. Respiratory arrhythmias were not seen in children who according to the Schellong-test were classified as stable in their cardiovascular system. The arrhythmias occurred mainly when the children showed signs of fatigue.     

The effectiveness of early endoscopy for upper gastrointestinal hemorrhage: a community-based analysis

OBJECTIVES: The effectiveness of upper endoscopy in unselected patients with upper gastrointestinal hemorrhage has not been well studied. This study was undertaken to identify factors associated with the performance of early endoscopy (ie, within 1 day of hospitalization) and, after adjusting for these factors, to determine associations between early endoscopy and in-hospital mortality, length of stay, and performance of surgery. METHODS: Subjects in this observational cohort study were 3,801 consecutive admissions with upper gastrointestinal hemorrhage to 30 hospitals in a large metropolitan region. Demographic and clinical data were abstracted from hospital records. A multivariable model based on factors that potentially could relate to the decision to perform endoscopy was developed to determine the propensity (0 to 100%) for early endoscopy in each patient. RESULTS: Early endoscopy was performed in 2,240 patients (59%), and although it was not associated with mortality after adjusting for severity of illness among all patients, it was associated with a higher risk of death for patients in the lowest propensity group. Early endoscopy was associated with a lower likelihood of upper gastrointestinal surgery in all patients and in the two highest propensity groups and with a shorter length of stay in the entire cohort and in all subgroups. CONCLUSIONS: In the absence of specific contraindications, early endoscopy should be considered because of associated reductions in length of stay and surgical intervention. Further studies are needed to identify subgroups in whom the procedure may be associated with adverse effects on survival.     

Effect of propranolol and nifedipine on maximal electroshock-induced seizures in mice: individually and in combination

To clarify the influence of the head-up position on cerebral oxygen metabolism during laparoscopy with CO2 insufflation in 12 patients who underwent laparoscopic cholecystectomy, changes in the concentrations of cerebral oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), total hemoglobin (total Hb) and oxidized cytochrome aa3 (Cyt aa3) were measured by use of near-infrared laser spectroscopy. Anesthesia was maintained with nitrous oxide (66%), oxygen, and sevoflurane. Pneumoperitoneum was maintained at an intraabdominal pressure of 10-12 mm Hg by use of CO2. Minute ventilation was adjusted to maintain end-tidal CO2 tension (P(ET)CO2) between 35 and 40 mm Hg during the procedure. Patients were moved from supine to the head-up (20 degree) position before intraabdominal manipulation. The concentration of HbO2 decreased significantly when patients were moved to the head-up position and 30 min thereafter. It remained significantly low after they were returned to the supine position and at the end of surgery. The concentration of Hb was unchanged during the study. Therefore, the concentration of total Hb decreased significantly when patients were moved to the head-up position, as well as 30 min thereafter. It remained significantly low after they were returned to the supine position and at the end of surgery. The concentration of Cyt aa3, however, did not change significantly during the study. These results suggest that the head-up position during laparoscopic cholecystectomy decreases cerebral HbO2 and total Hb.