Surgical management of bifocal femoral fractures: a systematic review and pooled analysis of treatment with a single implant versus double implants.

INTRODUCTION: Fractures of the proximal femur accompanied by a fracture of the femoral shaft are relatively rare, with a reported prevalence between 1 and 12%. Multiple surgical options are available, consisting of treatment with a single implant or with double implants. Controversy exists about the optimal management. A systematic review and pooled analysis were performed to assess the most reliable treatment for bifocal femoral fractures of the femur. MATERIALS AND METHODS: A literature search was conducted on July 15, 2022. Selected studies were screened on title and abstract by two researchers independently, and full texts were read by both authors. Emphasis was put on adverse events such as postoperative infection, healing complications, malalignment, and functional outcome using either a single implant or double implants. RESULTS: For the proximal femoral fractures, no significant difference could be confirmed for avascular necrosis of the femoral neck (5.1% for single implant and 3.8% for double implants), nonunion (6.4% for single implant and 7.8% for double implants), or varus malalignment (6.6% for single implant and 10.9% for double implants). This study also suggests that the number of implants is irrelevant for complications of the femoral shaft regarding the rates of postoperative infection and healing complications. Pooled rates of bone healing complications were 1.6-2.7-fold higher when patients were treated with a single implant, but statistical significance could not be confirmed. For hardware failure, revision surgery, leg length discrepancy, and functional outcome, no difference between the two groups was found either. CONCLUSIONS: The pooled proportions of all postoperative complications had overlapping confidence intervals; thus, no inference about a statistically significant difference on the number of implants used for treating ipsilateral fractures of the femur can be made. Both treatment groups showed a similar functional outcome at the last moment of follow-up, with more than 75% of the patients reporting a good outcome.

Impact of a history of metastases or synchronous metastases on survival in patients with locally recurrent rectal cancer.

AIM: Patients with locally recurrent rectal cancer (LRRC) frequently present with either synchronous metastases or a history of metastases. This study was conducted to evaluate whether LRRC patients without metastases have a different oncological outcome compared to patients with a history of metastases treated with curative intent or patients with potentially curable synchronous metastases. METHOD: All consecutive LRRC patients who underwent intentionally curative surgery between 2005 and 2017 in a large tertiary hospital were retrospectively reviewed and categorized as having no metastases, a history of (curatively treated) metastases or synchronous metastases. Patients with unresectable distant metastases were excluded from the analysis. RESULTS: Of the 349 patients who were analysed, 261 (75%) had no metastases, 42 (12%) had a history of metastases and 46 (13%) had synchronous metastases. The 3-year metastasis-free survival was 52%, 33% and 13% in patients without metastases, with a history of metastases, and with synchronous metastases, respectively (P < 0.001) A history of metastases did not influence overall survival (OS), but there was a trend towards a worse OS in patients with synchronous metastases compared with patients without synchronous metastases (hazard ratio 1.43; 95% CI 0.98-2.11). CONCLUSION: LRRC patients with a history of curatively treated metastases have an OS comparable to that in patients without metastases and should therefore be treated with curative intent. However, LRRC patients with synchronous metastases have a poor metastasis-free survival and worse OS; in these patients, an individualized treatment approach to observe the behaviour of the disease is recommended.

Prognostic implications of MRI-detected lateral nodal disease and extramural vascular invasion in rectal cancer.

BACKGROUND: Lateral nodal disease in rectal cancer remains a subject of debate and is treated differently in the East and the West. The predictive value of lateral lymph node and MRI-detected extramural vascular invasion (mrEMVI) features on oncological outcomes was assessed in this study. METHODS: In this retrospective cohort study, data on patients with cT3-4 rectal cancer within 8 cm from the anal verge were considered over a 5-year period (2009-2013). Lateral lymph node size, malignant features and mrEMVI features were evaluated and related to oncological outcomes. RESULTS: In total, 192 patients were studied, of whom 30 (15·6 per cent) underwent short-course radiotherapy and 145 (75·5 per cent) received chemoradiotherapy. A lateral lymph node short-axis size of 10 mm or more was associated with a significantly higher 5-year lateral/presacral local recurrence rate of 37 per cent, compared with 7·7 per cent in nodes smaller than 10 mm (P = 0·041). Enlarged nodes did not result in a higher 5-year rate of distant metastasis (23 per cent versus 27·7 per cent in nodes smaller than 10 mm; P = 0·563). However, mrEMVI positivity was related to more metastatic disease (5-year rate 43 versus 26·3 per cent in the mrEMVI-negative group; P = 0·014), but not with increased lateral/presacral recurrence. mrEMVI occurred in 46·6 per cent of patients with nodes smaller than 10 mm, compared with 29 per cent in patients with nodes of 10 mm or larger (P = 0·267). CONCLUSION: Although lateral nodal disease is more a local problem, mrEMVI mainly predicts distant recurrence. The results of this study showed an unacceptably high local recurrence rate in patients with a short axis of 10 mm or more, despite neoadjuvant (chemo)radiotherapy.

Preliminary results of a cohort study of induction chemotherapy-based treatment for locally recurrent rectal cancer.

BACKGROUND: A significant number of patients treated for locally recurrent rectal cancer have local or systemic failure, especially after incomplete surgical resection. Neoadjuvant treatment regimens in patients who have already undergone preoperative (chemo)radiotherapy for the primary tumour are limited. The objective of the present study was to evaluate the influence of a neoadjuvant regimen incorporating induction chemotherapy (ICT) in patients with locally recurrent rectal cancer who had preoperative (chemo)radiotherapy for the primary cancer or an earlier local recurrence. METHODS: Patients were treated with a sequential neoadjuvant regimen including three or four cycles of 5-fluorouracil and oxaliplatin-containing chemotherapy. When no progressive disease was found at evaluation, neoadjuvant treatment was continued with chemoradiation therapy (CRRT) using 30 Gy with concomitant capecitabine. If there was a response to ICT, the patient was advised to continue with systemic chemotherapy after CRRT as consolidation chemotherapy while waiting for resection. These patients were compared with patients who received CRRT alone in the same time interval. RESULTS: Of 58 patients who had ICT, 32 (55 per cent) had surgery with clear resection margins, of whom ten (17 per cent) exhibited a pathological complete response (pCR). The remaining 26 patients had 23 R1 and three R2 resections. In 71 patients who received CRRT, a similar rate of R0 (35 patients) and R1 (36) resection was found (P = 0·506), but only three patients (4 per cent) had a pCR (P = 0·015). CONCLUSION: The incorporation of ICT in neoadjuvant regimens for locally recurrent rectal cancer is a promising strategy.

Trends in incidence, health care consumption, and medical and productivity costs of femoral shaft fractures in the Netherlands between 2005 and 2019.

INTRODUCTION: Population-based knowledge on the occurrence of femoral shaft fractures is necessary for allocation of health care services, optimization of preventive measures, and research purposes. This nationwide study aimed to provide an overview on the incidence of femoral shaft fractures over a 15-year period and to gain insight into health care consumption and work absence with associated costs in the Dutch population. METHODS: Data of patients who sustained an acute femoral shaft fracture in the years 2005-2019 were extracted from the National Medical Registration of the Dutch Hospital Database. The incidence rate, hospital length of stay (HLOS), direct medical costs, productivity costs, and years lived with disability were calculated for age- and gender specific groups. RESULTS: A total of 15,847 patients with a femoral shaft fracture were included. The incidence rate increased with 13 % over this 15-year period (5.71/100,000 persons per year in 2005 and 6.47/100,000 in 2019). The mean HLOS per patient was 13.8 days in 2005-2009 versus 8.4 days in 2015-2019 for the entire group. Mean HLOS per patient increased with age (10.0 days for age group 0-9 and 12.7 days for age group >80), but declined over time from 13.6 days in 2005-2009 to 8.8 days in 2015-2019 in males, and from 13.7 days and to 8.2 days, respectively, in females. The costs due to work absence was higher in males. Cumulative health care costs were highest in females >80 years (8.4 million euros versus 1.6 million in males). CONCLUSION: The incidence rate of femoral shaft fractures increased over the past 15 years in the Netherlands. Mean HLOS per patient has decreased in all age groups and in both sexes. Health care costs were highest for female octogenarians.

Organ Preservation in Rectal Cancer: An Overview of the Dutch Perspective and Recent Developments.

Although current guidelines on rectal cancer treatment often recommend rectal resection with or without neoadjuvant (chemo)radiotherapy, there is growing interest in organ-preserving treatment approaches among patients and clinicians in the Netherlands. Currently, multiple ongoing studies are investigating the value of different non-operative treatment modalities to improve tumour response rates and increase the chance of successful organ preservation. Papillon contact X-ray brachytherapy is a promising treatment modality to improve the chance of organ preservation, which seems especially relevant for elderly and frail patients unable or refusing to undergo total mesorectal excision surgery. The elderly and frail patient with rectal cancer poses a significant challenge and warrants a thorough multidisciplinary approach to provide the most optimal organ-preserving treatment. In this overview, an insight into the Dutch perspectives and developments within the field of organ preservation and the set-up of a Papillon facility to complete the spectrum of organ-preserving treatment options in a tertiary referral centre for rectal cancer treatment has been provided.

Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study.

INTRODUCTION: The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics. METHODS: All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics. RESULTS: Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013). CONCLUSION: Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.

Ultrasound factors to predict the outcome of external cephalic version: a meta-analysis.

OBJECTIVE: To systematically review the medical literature reporting on ultrasound factors that can be predictive for the outcome of an attempt at external cephalic version (ECV). METHODS: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched. Studies reporting on potential ultrasound prognosticators and ECV success rates that allowed construction of a 2x2 table were selected. RESULTS: We selected 37 primary articles reporting on 7709 women. Posterior placental location (odds ratio (OR), 1.9; 95% CI, 1.5-2.4), complete breech position (OR, 2.3; 95% CI, 1.9-2.8) and an amniotic fluid index>10 (OR, 1.8; 95% CI, 1.5-2.1) were predictors of successful ECV. CONCLUSION: Success of an ECV attempt is associated with ultrasound parameters such as fetal position, amniotic fluid and placental location. This knowledge can be used to develop a prognostic model to predict successful ECV.

[Severe microcytic anemia with megaloblastic changes in the bone marrow. A hematological paradoxon?]. / Schwere mikrozytäre Anämie bei megaloblastären Veränderungen im Knochenmark : Ein hämatologisches Paradoxon?

We discuss the case of a 32 year-old male with severe microcytic anemia (hemoglobin 2,9 g/dl) and megaloblastic changes in the bone marrow. The patient reported of substantial dietary weight loss. The family history was positive for beta-thalassemia. Previous blood work showed iron deficiency with mild anemia. Further work-up verified beta-thalassemia minor and revealed severely decreased vitamin B12 levels with positive anti intrinsic-factor antibodies, pathognomonic for autoimmune pernicious anemia. The paradoxon therefore dissolved as a pernicious anemia with megaloblastic changes with microcytic erythrocytes due to beta-thalassemia.

Accuracy of body mass index in predicting pre-eclampsia: bivariate meta-analysis.

OBJECTIVE: The objective of this study was to determine the accuracy of body mass index (BMI) (pre-pregnancy or at booking) in predicting pre-eclampsia and to explore its potential for clinical application. DESIGN: Systematic review and bivariate meta-analysis. SETTING: Medline, Embase, Cochrane Library, MEDION, manual searching of reference lists of review articles and eligible primary articles, and contact with experts. POPULATION: Pregnant women at any level of risk in any healthcare setting. METHODS: Reviewers independently selected studies and extracted data on study characteristics, quality, and accuracy. No language restrictions. MAIN OUTCOME MEASURES: Pooled sensitivities and specificities (95% CI), a summary receiver operating characteristic curve, and corresponding likelihood ratios (LRs). The potential value of BMI was assessed by combining its predictive capacity for different prevalences of pre-eclampsia and the therapeutic effectiveness (relative risk 0.90) of aspirin. RESULTS: A total of 36 studies, testing 1,699,073 pregnant women (60,584 women with pre-eclampsia), met the selection criteria. The median incidence of pre-eclampsia was 3.9% (interquartile range 1.4-6.8). The area under the curve was 0.64 with 93% of heterogeneity explained by threshold differences. Pooled estimates (95% CI) for all studies with a BMI > or = 25 were 47% (33-61) for sensitivity and 73% (64-83) for specificity; and 21% (12-31) and 92% (89-95) for a BMI > or = 35. Corresponding LRs (95% CI) were 1.7 (0.3-11.9) for BMI > or = 25 and 0.73 (0.22-2.45) for BMI < 25, and 2.7 (1.0-7.3) for BMI > or = 35 and 0.86 (0.68-1.07) for BMI < 35. The number needed to treat with aspirin to prevent one case of pre-eclampsia ranges from 714 (no testing, low-risk women) to 37 (BMI > or = 35, high-risk women). CONCLUSIONS: BMI appears to be a fairly weak predictor for pre-eclampsia. Although BMI is virtually free of cost, noninvasive, and ubiquitously available, its usefulness as a stand-alone test for risk stratification must await formal cost-utility analysis. The findings of this review may serve as input for such analyses.

Accuracy of fibronectin tests for the prediction of pre-eclampsia: a systematic review.

The purpose of this study was to review systematically all studies that assessed the accuracy of maternal plasma fibronectin as a serum marker for early prediction of pre-eclampsia. We therefore assessed studies that reported on fibronectin as serum marker for pre-eclampsia before the 25th gestational week. For the selected studies, sensitivity and specificity were calculated and plotted in ROC-space. We included 12 studies, of which only 5 studies reported sufficient data to calculate accuracy estimates, such as sensitivity and specificity. These five studies reported on 573 pregnant women of whom 109 developed pre-eclampsia. At a sensitivity of at least 50%, specificities ranged between 72 and 96% for cellular fibronectin. For total fibronectin, these numbers were 42-94%. Fibronectin seems to be a promising marker for the prediction of pre-eclampsia, however, further studies are needed to determine whether the accuracy of this test is sufficient to be clinically relevant.

Comparison of symptoms and presentation of women with benign, low malignant potential and invasive ovarian tumors.

OBJECTIVES: To describe symptoms, delay in presentation and reasons for non-presentation among women diagnosed with benign, low malignant potential and malignant ovarian tumors. METHODS: Study participants included 457 women who underwent surgery for an ovarian tumor in Queensland, Australia, between July 1999 and February 2002 (244 with invasive cancer, 62 with low malignant potential tumors, and 151 with benign ovarian tumors). Women were contacted a minimum of three months post-diagnosis. Information concerning symptoms and presentation history was obtained via interview. RESULTS: Overall, only 8% of the women were asymptomatic at the time of their diagnosis. Women with invasive cancer reported a greater number of symptoms (3.1 and 3.6 for Stages I-II and III-IV, respectively) than women with benign or low malignant potential tumors (2.8 and 2.2 respectively; p < 0.0001). Women with invasive disease were more likely to experience weight loss or gain, general malaise, chest/respiratory pain, abdominal swelling and bowel symptoms than women with benign ovarian tumors, however the symptom pattern for early- and late-stage invasive ovarian cancer could not be clearly differentiated. There was no suggestion that women with advanced stage disease had delayed longer before presenting to their doctor. The most common reasons given for not telling their doctor about specific symptoms were the woman's perception that the symptom was not serious enough, it was mild or intermittent, or was related to normal physical changes associated with age or menopause. CONCLUSIONS: We found only marginal differences in the symptom patterns of early and advanced stage invasive cancer. Delay in presentation was not associated with more advanced disease suggesting that earlier diagnosis may not increase the proportion of cancers diagnosed at an early stage.

Mixed rosette assay for the detection of T mu and T gamma lymphocytes.

A mixed rosette assay is described for simultaneous detection of T lymphocytes and lymphocytes bearing receptors for the Fc Fragments of IgM (RFc mu) or IgG (RFc gamma) in unfractionated lymphocyte suspensions. For optimal detection of T lymphocytes, treatment of sheep erythrocytes with neuraminidase was necessary. ox erythrocytes labelled with fluorescein isothiocyanate and sensitized with either rabbit IgM or rabbit IgG anti-ox antibodies served as indicator erythrocytes for RFc mu or RFc gamma bearing lymphocytes. In periphral blood the percentage of RFc mu bearing lymphocytes was the same whether determined directly after isolation or after overnight incubation at 37 degrees C. Ratios of non-fluoresceinated sheep erythrocytes to senanti-ox antibodies served as indicator erythrocytes for RFc mu or RFc gamma bearing lymphocytes. In periphral blood the percentage of RFc mu bearing lymphocytes was the same whether determined directly after isolation or after overnight incubation at 37 degrees C. Ratios of non-fluoresceinated sheep erythrocytes to senanti-ox antibodies served as indicator erythrocytes for RFc mu or RFc gamma bearing lymphocytes. In periphral blood the percentage of RFc mu bearing lymphocytes was the same whether determined directly after isolation or after overnight incubation at 37 degrees C. Ratios of non-fluoresceinated sheep erythrocytes to sensitized fluoresceinated ox erythrocytes are critical in the mixed rosette assay; for simultaneous detection of T lymphocytes and RFc mu bearing lymphocytes 1 : 1, and for T lymphocytes and RFc gamma bearing lymphocytes 2 : 1. In both assays the rosette suspension was preincubated for 10 min at 37 degrees C and then centrifuged at 200 X g for 5 min. For optimal simultaneous detection of T lymphocytes and RFc mu bearing lymphocytes incubation at room temperature for at least 2 h was necessary and for T lymphocytes and RFc gamma bearing lymphocytes incubation at room temperature for at least 2 h was necessary and for T lymphocytes and RFc gamma bearing lymphocytes incubation at 4 degrees C for at least 2 h was essential. The percentages of RFc mu or RFc gamma bearing lymphocytes (T mu and T gamma respectively) in the T lymphocyte population determined by mixed rosette assay did not differ significantly from the percentages of RFc mu and RFc gamma bearing lymphocytes in lymphocyte suspensions enriched in T cells by E-rosette sedimentation. The mixed rosette assay is suitable for detection of T mu and T gamma cells in immune deficiency and auto-immune diseases and for analysis of the mononuclear cells in lymphoreticular malignancies.

An optimized software framework for real-time, high-throughput tracking of spherical beads.

Numerous biophysical techniques such as magnetic tweezers, flow stretching assays, or tethered particle motion assays rely on the tracking of spherical beads to obtain quantitative information about the individual biomolecules to which these beads are bound. The determination of these beads' coordinates from video-based images typically forms an essential component of these techniques. Recent advances in camera technology permit the simultaneous imaging of many beads, greatly increasing the information that can be captured in a single experiment. However, computational aspects such as frame capture rates or tracking algorithms often limit the rapid determination of such beads' coordinates. Here, we present a scalable and open source software framework to accelerate bead localization calculations based on the CUDA parallel computing framework. Within this framework, we implement the Quadrant Interpolation algorithm in order to accurately and simultaneously track hundreds of beads in real time using consumer hardware. In doing so, we show that the scatter derived from the bead tracking algorithms remains close to the theoretical optimum defined by the Cramer-Rao Lower Bound. We also explore the trade-offs between processing speed, size of the region-of-interests utilized, and tracking bias, highlighting in passing a bias in tracking along the optical axis that has previously gone unreported. To demonstrate the practical application of this software, we demonstrate how its implementation on magnetic tweezers can accurately track (with ∼1 nm standard deviation) 228 DNA-tethered beads at 58 Hz. These advances will facilitate the development and use of high-throughput single-molecule approaches.

Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling.

OBJECTIVES: To investigate the accuracy of predictive tests for pre-eclampsia and the effectiveness of preventative interventions for pre-eclampsia. Also to assess the cost-effectiveness of strategies (test-intervention combinations) to predict and prevent pre-eclampsia. DATA SOURCES: Major electronic databases were searched to January 2005 at least. REVIEW METHODS: Systematic reviews were carried out for test accuracy and effectiveness. Quality assessment was carried out using standard tools. For test accuracy, meta-analyses used a bivariate approach. Effectiveness reviews were conducted under the auspices of the Cochrane Pregnancy and Childbirth Group and used standard Cochrane review methods. The economic evaluation was from an NHS perspective and used a decision tree model. RESULTS: For the 27 tests reviewed, the quality of included studies was generally poor. Some tests appeared to have high specificity, but at the expense of compromised sensitivity. Tests that reached specificities above 90% were body mass index greater than 34, alpha-foetoprotein and uterine artery Doppler (bilateral notching). The only Doppler test with a sensitivity of over 60% was resistance index and combinations of indices. A few tests not commonly found in routine practice, such as kallikreinuria and SDS-PAGE proteinuria, seemed to offer the promise of high sensitivity, without compromising specificity, but these would require further investigation. For the 16 effectiveness reviews, the quality of included studies was variable. The largest review was of antiplatelet agents, primarily low-dose aspirin, and included 51 trials (36,500 women). This was the only review where the intervention was shown to prevent both pre-eclampsia and its consequences for the baby. Calcium supplementation also reduced the risk of pre-eclampsia, but with some uncertainty about the impact on outcomes for the baby. The only other intervention associated with a reduction in RR of pre-eclampsia was rest at home, with or without a nutritional supplement, for women with normal blood pressure. However, this review included just two small trials and its results should be interpreted with caution. The cost of most of the tests was modest, ranging from 5 pounds for blood tests such as serum uric acid to approximately 20 pounds for Doppler tests. Similarly, the cost of most interventions was also modest. In contrast, the best estimate of additional average cost associated with an average case of pre-eclampsia was high at approximately 9000 pounds. The results of the modelling revealed that prior testing with the test accuracy sensitivities and specificities identified appeared to offer little as a way of improving cost-effectiveness. Based on the evidence reviewed, none of the tests appeared sufficiently accurate to be clinically useful and the results of the model favoured no-test/treat-all strategies. Rest at home without any initial testing appeared to be the most cost-effective 'test-treatment' combination. Calcium supplementation to all women, without any initial testing, appeared to be the second most cost-effective. The economic model provided little support that any form of Doppler test has sufficiently high sensitivity and specificity to be cost-effective for the early identification of pre-eclampsia. It also suggested that the pattern of cost-effectiveness was no different in high-risk mothers than the low-risk mothers considered in the base case. CONCLUSIONS: The tests evaluated are not sufficiently accurate, in our opinion, to suggest their routine use in clinical practice. Calcium and antiplatelet agents, primarily low-dose aspirin, were the interventions shown to prevent pre-eclampsia. The most cost-effective approach to reducing pre-eclampsia is likely to be the provision of an effective, affordable and safe intervention applied to all mothers without prior testing to assess levels of risk. It is probably premature to suggest the implementation of a treat-all intervention strategy at present, however the feasibility and acceptability of this to women could be explored. Rigorous evaluation is needed of tests with modest cost whose initial assessments suggest that they may have high levels of both sensitivity and specificity. Similarly, there is a need for high-quality, adequately powered randomised controlled trials to investigate whether interventions such as advice to rest are indeed effective in reducing pre-eclampsia. In future, an economic model should be developed that considers not just pre-eclampsia, but other related outcomes, particularly those relevant to the infant such as perinatal death, preterm birth and small for gestational age. Such a modelling project should make provision for primary data collection on the safety of interventions and their associated costs.

Lymphocyte subpopulations in rheumatoid arthritis. An immunological, enzyme histochemical and morphological study.

Peripheral blood lymphocytes (PBL) and synovial fluid lymphocytes ( SFL ) of patients with rheumatoid arthritis (RA) were examined with monoclonal antibodies, with coated ox red blood cells for the expression of Fc receptors for IgG or IgM (T mu and T gamma cells), and incubated for the demonstration of alpha- naphtyl acetate esterase and acid phosphatase. Equal percentages of OKT4 and OKT8 PBL were found in clinically active and inactive RA patients, and in healthy controls, but decreased percentages of OKT4 and increased percentages of OKT8-positive lymphocytes were found among the SFL . The percentages of T mu and T gamma cells, the presence of HLA-DR membrane antigens on T lymphocytes as well as the staining pattern for the enzymes revealed that SFL of patients with RA were highly activated, compared to PBL of RA patients and healthy controls. It can be concluded from this study that a single determination of OKT4 and OKT8-positive lymphocytes in the peripheral blood of RA patients has no predictive value for disease activity. However, the results of the experiments on T lymphocyte-activation clearly showed preferential activation of SFL compared to PBL, indicating that activation of lymphocytes occurs at the site of inflammation.

Morphological aspects of T cell subpopulations in human blood: characterization of the cerebriform mononuclear cells in healthy individuals.

Cerebriform mononuclear cells (CMC) constitute a morphologically distinct subpopulation of T cells in healthy individuals. They are characterized ultrastructurally by a highly indented nucleus, a high nucleus-to-cytoplasm ratio, condensed chromatin along the nuclear membrane and a scanty cytoplasm. In order to characterize the peripheral blood CMC by enzyme-histochemistry and membrane characteristics, lymphocyte fractions enriched for T cells, T mu cells, T gamma cells and T cells without Fc mu and Fc gamma receptors (T0 cell fraction), or depleted of T cells, were investigated for the presence of alpha-naphthylacetate esterase and acid phosphatase at light and electron microscopic levels. CMC were found exclusively in the T mu-enriched and T0 cell fraction, indicating that these cells have either an Fc mu receptor or no Fc receptor at all. Except for their nuclear indentation, both the CMC in the T mu-enriched fractions and the CMC in the T0 fractions ultrastructurally resembled the characteristic cell in the T mu fraction (TM-type cell), but differed from the characteristic cell in the T gamma fraction (TG-type cell). Moreover, like the TM-type cells all CMC showed paranuclear dots of alpha-naphthylacetate esterase and acid phosphatase activity in their cytoplasm. From these observations it was concluded that CMC without Fc mu receptors were either stimulated T mu cells or precursor T mu cells. Thus CMC in healthy individuals constitute a distinct subpopulation of T cells not only morphologically but also histochemically and immunologically.

T lymphocyte subpopulations in rheumatoid arthritis.

The number of various lymphocyte subpopulations in the peripheral blood of 28 patients with definite rheumatoid arthritis (RA) were studied. The results were correlated with the disease activity, as assessed by the Ritchie index, erythrocyte sedimentation rate and clinical impression. Patients with active RA showed decreased numbers of T mu lymphocytes, strongly increased numbers of Tnull lymphocytes and slightly increased percentages of Fc gamma lymphocytes as compared to 22 healthy donors. Patients with inactive RA had similar, less striking, but significant changes in T mu and Tnull lymphocytes, but in contrast to patients with active RA had Increased numbers of T gamma lymphocytes. The imbalances in T mu and Tnull cells in patients with RA might be explained by endogenous T mu cell activation, resulting in increased numbers of Tnull cells.