Pathogenesis and diagnosis of human meningococcal disease using immunohistochemical and PCR assays

Neisseria meningitidis remains the leading cause of fatal sepsis. Cultures may not be available in fulminant fatal cases. An immunohistochemical assay for N meningitidis was applied to formalin-fixed samples from 14 patients with meningococcal disease. Histopathologic findings in 12 fatal cases included interstitial pneumonitis, hemorrhagic adrenal glands, myocarditis, meningitis, and thrombi in the glomeruli and choroid plexus. Meningeal inflammation was observed in 6 patients. Skin biopsies of 2 surviving patients showed leukocytoclastic vasculitis and cellulitis. By using immunohistochemical analysis, meningococci and granular meningococcal antigens were observed inside monocytes, neutrophils, and endothelial cells or extracellularly. By using real-time polymerase chain reaction (PCR) on formalin-fixed tissue samples, meningococcal serogroup determination was possible in 11 of 14 cases (8 serogroup C, 2 Y, and 1 B). Diagnosis and serogrouping of N meningitidis can be performed using immunohistochemical analysis and PCR on formalin-fixed tissue samples. Immunohistochemical analysis determined the distribution of meningococci and meningococcal antigens in tissue samples, allowing better insights into N meningitidis pathogenesis.     

Surgery-attached psychogeriatric nurses: an evaluation of psychiatric nurses in the primary care team

Aspects of the work of five community psychiatric nurses are examined by means of a questionnaire completed by the nurses for a sample of 50 patients. Information sharing and a close working relationship with the general practitioner, skills relating to assessment and psychological support of patients, organization of care by other agencies, a detailed knowledge of community agencies, and a capacity for interdisciplinary working were all found to be important. Tasks relating to body care were reported in only a small number of cases. The nurses saw themselves as advising on the planning of patient management and the selection of medication in a substantial minority of cases. The original brief had been to care for psychogeriatric patients but a third of the patients fell into a younger age group. These findings are discussed in connection with their implications for the future training of nurses and the relationship between primary care teams and local psychiatric services.     

Detecting depressive disorders in drug abusers : A comparison of screening instruments

Previous investigators have reported a high prevalence of depressive symptoms in drug-dependent patients. Given the responsiveness of depressive disorders to both psychological and pharmacological treatments, it is desirable to find an economical, efficient screening instrument to detect depressive disorders in this population. In this study, 6 depression symptom screening scales (Beck Depression Inventory, Hamilton Depression Scale, Raskin Depression Scale, Degree of Illness Rating, Symptom Checklist 90 Overall, and Depression Subscale) based on either clinician interview or patient self report, were compared according to their utility in detecting cases of depression among 64 applicants for treatment at a substance abuse treatment unit of a community mental health center. The criteria for a case of depression were the Research Diagnostic Criteria (RDC) which are specified and operationalized. Cases identified using previously described cutoff scores on the screening scales were compared to rates based on the RDC and sensitivity and specificity were determined. The results showed that: (1) although the sensitivity of the symptom scales was applicable, ranging from 65--94%, the specificity was less impressive, ranging from 39--61%, and (2) the Beck Depression Inventory, a 13-item patient self report was the most sensitive and specific and is recommended for screening drug-dependent populations for depression.     

Null mutation in human ciliary neurotrophic factor gene confers higher body mass index in males

Ciliary neurotrophic factor (CNTF) administration reduces weight in leptin-resistant mice via the signalling pathway normally activated by leptin. A G>A null mutation in the CNTF gene results in complete absence of protein. We hypothesised that absence of CNTF could lead to diminished initiation of anorectic pathways, with consequent increase in body mass. In 575 Caucasian men aged 59-73 years, the A/A genotype (frequency 1.9%) was associated with a 10 kg increase in weight (P=0.03, 2 df) and 3 kg/m(2) greater BMI (P=0.02, 2 df). There was no effect in women. The CNTF G>A null mutation therefore confers a moderate effect on obesity in males of A/A genotype, who represent 1% of the general population.     

Regulation of human erythrocyte metabolism by insulin: cellular distribution of 6-phosphofructo-1-kinase and its implication for red blood cell function

Human erythrocytes are highly specialized cells whose function is oxygen transport. These cells' sole metabolic source of energy is the fermentation of glucose via glycolysis. They contain an active insulin receptor and respond to insulin by increasing phosphorylation of tyrosine residues in several proteins. However, no metabolic effects have yet been associated with activation of this receptor in human erythrocytes. Here, we show that insulin increases the rate of glycolysis in human erythrocytes. Lactate production increased 56 and 173% in the presence of 10 and 100 nM insulin, respectively. A higher insulin concentration (1000 nM) partially reversed the stimulation of glycolysis. These effects occur through activation of the key glycolytic enzyme 6-phosphofructo-1-kinase, which exhibits the same pattern of modulation by insulin as seen for glycolytic flux. This modulation also occurs physiologically since ex vivo experiments revealed 50% stimulation of 6-phosphofructo-1-kinase (PFK) activity following a high carbohydrate meal. Insulin increases phosphorylation of PFK and redistributes the enzyme in red blood cells, causing it to detach from the erythrocyte membrane: upon insulin stimulation, the amount of enzyme associated with the plasma decreases by 86%. Detachment is a common mechanism of enzyme activation. As a consequence, insulin prevents up to 68% of red cells hemolysis. These results show that insulin regulates erythrocyte glycolysis and viability and suggest that this regulation is associated to other erythrocyte functions such as oxygen transport. Finally, we suggest that this regulatory mechanism might be compromised in patients with diabetes mellitus.     

Experimental cutaneous leishmaniasis. III. Effects of thymectomy on the course of infection of CBA mice with leishmania tropica

This paper describes the course of infection and the immunological response in thymus-deprived and normal CBA mice after intradermal inoculation with promastigotes of L. tropica.

Infection of normal mice resulted in the development of a cutaneous ulcer healing within 12 weeks. As the infection progressed and the draining lymph nodes increased in weight, changes in the paracortical and follicular regions were accompanied by the development of delayed hypersensitivity and the production of antibodies detectable by immunofluorescence and a parasite agglutination test.

Lesions in thymectomized irradiated mice healed more slowly and the draining lymph nodes were smaller than in normal mice. Follicular reactions were feeble and paracortical activity depressed. The most noticeable feature of these lymph nodes was a persistent and intense macrophage infiltration. Delayed hypersensitivity and antibodies detectable by immunofluorescence were correspondingly low; but parasite agglutinating antibody was not depressed. The course of infection and immunological response of a control group of sham thymectomized, irradiated mice resembled that of normal mice.

These experiments indicate that thymus-dependent cell populations play an important role in the response of mice to infection with L. tropica.

     

Metabolic polymorphisms and the micronucleus frequency in buccal epithelium of adolescents living in an urban environment

Micronuclei and other biomarkers were evaluated in oral cells from 11- to 16-year-old girls living in a foster home in the central area of México City. Variables analyzed for possible association with these biomarkers include smoking habits, body mass index, metabolic polymorphisms for NAT1 and GSTM1 and whether the cells were obtained from the cheek or pharynx. The results indicated that individuals having the NAT1*10 homozygous genotype showed a significant increase in chromatin buds and binucleated cells. When the damage in the cheek was compared with damage in the pharynx, a significant increase in micronuclei and binucleated cells was found for the latter tissue in all the individuals analyzed.     

The impact of testing accommodations on MCAT scores: descriptive results.

PURPOSE: Medical College Admission Test (MCAT) examinees with disabilities who receive accommodations receive flagged scores indicating nonstandard administration. This report compares MCAT examinees who received accommodations and their performances with standard examinees. METHOD: Aggregate history records of all 1994-2000 MCAT examinees were identified as flagged (2,401) or standard (297,880), then further sorted by race/ethnicity (broadly identified as underrepresented minority and non-URM, at the time of testing) and gender. Those with flagged scores were also classified by disability (LD = learning disability, ADHD = attention deficit hyperactivity disorder, LD/ADHD = learning disability and attention deficit hyperactivity disorder, and Other = other disability) and type of accommodation. Mean MCAT scores were calculated for all groups. A group of 866 examinees took the MCAT first as a standard administration and subsequently with accommodations. In a separate analysis, their two sets of scores were compared. RESULTS: Less than 1% of examinees (2,401) had accommodations; of these, 55% were LD, 17% ADHD, 5% LD/ADHD, and 23% Other. Extended time was the most frequently provided accommodation. Mean flagged scores slightly exceeded mean standard scores on all MCAT sections. Examinees who retook the MCAT with accommodations after a standard administration increased their scores by six points, quadrupling the average gain Standard-Standard retest cohort from another study. CONCLUSION: The small but statistically significant different higher flagged scores may reflect either appropriate compensation or overly generous accommodations. Extended time had a positive impact on the scores of those who retested with this accommodation. The validity the flagged MCAT in predicting success in medical school is not known, and further investigation is underway.