875 Cases of bacterial meningitis: Diagnostic procedures and the impact of preadmission antibiotic therapy Part III of a three-part series

Data on the bacteriological findings, diagnostic measures and clinical course of 875 patients with bacterial meningitis are presented. Findings from the medical records and from a follow-up questionnaire survey of 667 of these cases revealed no significant difference between patients treated with antibiotics before admission (pretreated) and those who were not treated before admission (non-pretreated) with respect to clinical condition on admission, mortality and late sequelae. Pretreatment was, however, associated with a longer duration of symptoms. Apart from cases due to Neisseria meningitidis, there were no significant differences in diagnostic findings between pretreated and non-pretreated cases. In the group of pretreated meningococcal patients, however, positive blood cultures, pleiocytosis in the cerebrospinal fluid (CSF) and positive cultures from sites other than blood and CSF were less frequent than in the non-pretreated cases.     

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Differential effects of nitric oxide on erythroid and myeloid colony growth from CD34+ human bone marrow cells

Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and immune systems. In previous work, we have demonstrated that NO inhibits the growth and induces the monocytic differentiation of cells of the HL- 60 cell line. We have also demonstrated that NO inhibits the growth of acute nonlymphocytic leukemia cells freshly isolated from untreated patients and increases monocytic differentiation antigens in some. In the present work, we studied the effect of NO on the growth and differentiation of normal human bone marrow cells in vitro. Mononuclear cells isolated from human bone marrow were cultured in semisolid media and treated with the NO-donating agents sodium nitroprusside (SNP) or S- nitroso-acetyl penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased colony-forming unit-erythroid (CFU-E) and colony-forming unit- granulocyte macrophage (CFU-GM) formation by 34% to 100%. When CD34+ cells were examined, we noted that these cells responded to SNP and SNAP differently than did the mononuclear cells. At a concentration range of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30% to 75%. However, at the same concentration range, SNP increased the number of CFU-GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inhibited the growth of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect CFU-GM. At higher concentrations, SNAP inhibited the growth of CFU-GM. Although SNP increased intracellular levels of cGMP in bone marrow cells, increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not reproduce the observed NO effects on bone marrow colonies. These results demonstrate that NO can influence the growth and differentiation of normal human bone marrow cells. NO (generated in the bone marrow microenvironment) may play an important role modulating the growth and differentiation of bone marrow cells in vivo.     

von Willebrand factor propeptide to antigen ratio identifies platelet activation and reduced von Willebrand factor survival phenotype in mice

Essentials

• Reduced survival of von Willebrand factor (VWF) in plasma causes type 1C von Willebrand disease.
• Blood was collected from mouse strains by various methods and VWF propeptide and antigen assayed.
• VWF propeptide to antigen ratio identifies a reduced VWF survival phenotype in mice.
• This ratio validates the acceptability of murine blood samples for coagulation studies.

Summary

Background

Reduced plasma survival of von Willebrand factor (VWF) is characteristic of patients with type 1C von Willebrand disease (VWD). These subjects can be identified by an increased steady‐state ratio of plasma VWF propeptide (VWFpp) to VWF antigen (VWF:Ag). A similar phenotype occurs in mice with the Mvwf1 allele.

Objectives

To (i) determine if the VWFpp/VWF:Ag ratio can be used to identify a ‘type 1C’ phenotype in mice, (ii) determine the most reliable method for murine blood sampling, and (iii) identify the source of VWF released during problematic blood collection.

Methods

‘Platelet‐VWF’ and ‘endothelial‐VWF’ mice were generated by bone marrow transplantation between C57BL/6J and VWF‐/‐ mice. Several blood sampling methods were used and murine VWFpp and VWF:Ag levels determined. Plasma and platelet VWF:Ag and VWFpp, VWF multimers and VWF half‐life were examined in mouse strains with and without Mvwf1.

Results

A single retro‐orbital bleed and vena cava collection were found to be the optimal methods of blood collection. Problematic collection resulted in release of VWF from platelets and endothelium. The VWFpp/VWF:Ag ratio identified strains of mice with reduced VWF survival.

Conclusion

Assay of murine VWFpp and VWF:Ag has utility in determining the acceptability of murine blood samples for coagulation testing and in identification of a reduced VWF survival phenotype in mice.

     

Plasma-sulfated C21-steroids increase during the periovulatory period in female common wolffish and are influenced by temperature during vitellogenesis

Plasma concentrations of steroids during the periovulatory period were measured in female common wolffish reared at three different temperatures. Steroids were quantified by radioimmunoassay (RIA). Two "broad-spectrum specificity" RIAs-one which detects C21-steroids with a 17,20beta-dihydroxyl configuration (17,20beta-steroids) and the other which detects C21-steroids with a 5beta-reduced, 3alpha-hydroxyl configuration (5beta,3alpha-steroids)-picked up very large amounts of cross-reacting material (1.7 microg ml(-1) in one fish) in the sulfate fraction of plasma from ovulating females. Reverse-phase high-performance liquid chromatography and thin-layer chromatography revealed two major steroids: 5beta-pregnane-3alpha,17,20beta-triol (80%) and 5beta-pregnane-3beta,17,20beta-triol (20%). The sulfated forms of these steroids were elevated 4 to 6 days before and during ovulation, compared with those of females in vitellogenic and postspawning condition, in which concentrations were below 2.0 ng ml(-1). In the three groups of fish held at 4, 8, and 12 degrees C during vitellogenesis, but returned to 4 degrees C just prior to the spawning season, the mean concentrations of sulfated 17,20beta-steroids in ovulating females were 530, 635, and 325 ng ml(-1), respectively. The corresponding concentrations of free 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P; the maturation-inducing steroid in many teleosts) were 0.88, 0.86, and 0.57 ng ml(-1), respectively. Only minute amounts of 17,20beta,21-P and its sulfated derivatives were detected. Significantly lower steroid concentrations in the 12 degrees C group indicate that steroid synthesis and/or metabolism during the periovulatory period are influenced by the temperature experienced during vitellogenesis. In male fish, plasma concentrations of both sulfated 17,20beta-steroids and free 17,20beta-P were low (< 2.0 ng ml(-1)) at all times.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Vitamin supplements among women with adenomatous polyps and cancer of the colon

Chemoprevention of various epithelial cancers with vitamins or minerals has been the subject of multiple intervention trials to assess the impact of supplementation. These include several trials in patients with adenomatous polyps of the colon, a precursor lesion for colon cancer. The authors interviewed 255 women who underwent colonoscopy at Columbia Presbyterian Medical Center between 1983 and 1985 with a telephone-administered structured questionnaire. Eleven interviews were excluded for various reasons. Overall, 57.7 percent of the 244 interviewees used vitamin pills on a regular basis (at least once a week for a year); 6.6 percent of the interviewees used vitamin A, 20.7 percent used vitamin C, and 16.2 percent used vitamin E. There were no statistically significant differences in vitamin usage among women with adenomatous polyps of the colon (105 cases), women with colon cancer (56 cases), and women without colonic neoplasia (83 cases). Despite widespread use of supplementary vitamins, this study failed to demonstrate major benefits in preventing colon polyps or cancer. Read in part at the Tenth Meeting of the American Society for Preventive Oncology, Bethesda, Maryland, March 7, 1986. Supported by NCI Grant No.CA37196, an American Cancer Society Junior Faculty Fellowship (AIN), a grant from the Andrew Mellon Foundation, and an internship from the Health Research Training Program of the NYC Department of Health (CMJ).     

Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns

White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We stratified on Aβ1-42 pathology (Aβ+/−) and analyzed group differences, as well as associations with Framingham Risk Score for cardiovascular disease (FRS-CVD) and age. Occipital PWMH (p = 0.001) and occipital DWMH (p = 0.003) loads were increased in SCD-Aβ+ compared with Aβ− controls. In MCI-Aβ+ compared with Aβ− controls, there were differences in global WMH (p = 0.003), as well as occipital DWMH (p = 0.001) and temporal DWMH (p = 0.002) loads. FRS-CVD was associated with frontal PWMHs (p = 0.003) and frontal DWMHs (p = 0.005), after adjusting for age. There were associations between global and all regional WMH loads and age. In summary, posterior WMH loads were increased in SCD-Aβ+ and MCI-Aβ+ cases, whereas frontal WMHs were associated with vascular risk. The differences in WMH topography support the use of regional WMH load as an early-stage marker of etiology.