The prevalence, incidence, and progression of radiographic thumb base osteoarthritis in a population-based cohort: the Rotterdam Study.

OBJECTIVE: To describe the prevalence, incidence, and progression of radiographic thumb carpometacarpal (CMC-1) and trapezioscaphoid (TS) radiographic osteoarthritis (ROA) in the general Dutch population aged ≥55y. DESIGN: Data were from the first and second cohort of the Rotterdam Study (1990-2005, 4-12 years follow-up, age 55+). Participants underwent bilateral radiographs at baseline (N = 7792) and follow-up (N = 3804), read for Kellgren-Lawrence (K-L) grade. ROA was defined on the joint level as K-L grade ≥2. The prevalence was assessed at baseline, incidence at follow-up in those free of ROA at baseline, and progression in those with ROA. Differences based on sex and age were evaluated using logistic regression models. RESULTS: At baseline, 1977 (25.3%) had CMC-1 ROA and 1133 (14.5%) TS ROA. The prevalence was higher in females for CMC-1 (aOR = 1.98 95%CI [1.77-2.21]) and TS ROA (aOR = 2.00 [1.74-2.29]) and increased for every year of age (CMC-1 ROA 1.08 [1.07-1.08]) (TS ROA 1.06 [1.05-1.07]). Most (437/512; 85.4%) incident cases of CMC-1 ROA (2994 at risk) were mild (K-L = 2), whereas most (145/167; 86,8%) incident cases of TS ROA (3311 at risk) were moderate to severe (K-L = 3/4). CMC-1 ROA progression was mostly (88/100; 88.0%) seen in the K-L 2 group at baseline, whereas that was (4/17; 23.5%) for TS ROA. CONCLUSION: CMC-1 ROA and TS ROA are prevalent in the general Dutch population. While incident CMC-1 ROA was primarily mild, incident TS ROA was more often moderate to severe. CMC-1 ROA was a strong predictor for incident TS ROA.

The impact of psychosocial variables on initial presentation and surgical outcome for ulnar-sided wrist pathology: a cohort study with 1-year follow-up.

AIMS: Ulnar-sided wrist pain has historically been equated to lower-back pain of wrist surgery. Little is known about the relationship between psychosocial profile and the manifestation of ulnar-sided wrist pathology and their treatment outcomes. This study aimed to determine the impact of pain catastrophising, psychological distress, illness perception, and patients' outcome expectations on patient-reported pain and hand function before and one year after surgery for ulnar-sided wrist pathology. PATIENTS AND METHODS: We included patients who underwent surgical treatment for ulnar-sided wrist pathology. Before surgery, patients completed the Pain Catastrophising Scale (PCS), Patient Health Questionnaire (PHQ), Brief-Illness Perception Questionnaire (B-IPQ), and Credibility/Expectancy Questionnaire (CEQ). Pain and dysfunction were assessed before (n = 423) and one year after surgery (n = 253) using the Patient Rated Wrist/Hand Evaluation (PRWHE). Hierarchical linear regression was used to assess the relationship between psychosocial factors and the preoperative PRWHE score, postoperative PRWHE score, and change in PRWHE. RESULTS: Psychosocial variables explained an additional 35% of the variance in preoperative PRWHE scores and 18% on postoperative scores. A more negative psychosocial profile was associated with higher (worse) preoperative PRWHE scores (PCS: B = 0.19, CI = [0.02-0.36]; B-IPQ Consequences: B = 3.26, CI = 2.36-4.15; and B-IPQ Identity, B = 1.88 [1.09-2.67]) and postoperative PRWHE scores (PCS: B = 0.44, CI = [0.08-0.81]) but not with the change in PRWHE after surgery. Higher treatment expectations were associated with a lower (better) postoperative PRWHE score (CEQ expectancy: B = -1.63, CI = [-2.43;-0.83]) and a larger change in PRWHE scores (B =|1.62|, CI = [|0.77; 2.47|]). CONCLUSION: A more negative psychosocial profile was associated with higher pain levels and dysfunction preoperatively and postoperatively. However, these patients showed similar improvement as patients with a more feasible psychosocial profile. Therefore, patients should not be withheld from surgical treatment based on their preoperative psychosocial profile alone. Boosting treatment expectations might further improve treatment outcomes. LEVEL OF EVIDENCE: III (Cohort study).

Outcomes of ulna shortening osteotomy: a cohort analysis of 106 patients.

BACKGROUND: Ulna shortening osteotomy (USO) for ulnar impaction syndrome (UIS) aims to improve pain and function by unloading the ulnar carpus. Previous studies often lack validated patient-reported outcomes or have small sample sizes. The primary objective of this study was to investigate patient-reported pain and hand function at 12 months after USO for UIS. Secondary objectives were to investigate the active range of motion, grip strength, complications, and whether outcomes differed based on etiology. MATERIALS AND METHODS: We report on 106 patients with UIS who received USO between 2012 and 2019. In 44 of these patients, USO was performed secondary to distal radius fracture. Pain and function were measured with the Patient Rated Wrist/Hand Evaluation (PRWHE) before surgery and at 3 and 12 months after surgery. Active range of motion and grip strength were measured before surgery and at 3 and 12 months after surgery. Complications were scored using the International Consortium for Health Outcome Measurement Complications in Hand and Wrist conditions (ICHAW) tool. RESULTS: The PRWHE total score improved from a mean of 64 (SD = 18) before surgery to 40 (22) at 3 months and 32 (23) at 12 months after surgery (P < 0.001; effect size Cohen's d = -1.4). There was no difference in the improvement in PRWHE total score (P = 0.99) based on etiology. Also, no clinically relevant changes in the active range of motion were measured. Independent of etiology, mean grip strength improved from 24 (11) before surgery to 30 (12) at 12 months (P = 0.001). Sixty-four percent of patients experienced at least one complication, ranging from minor to severe. Of the 80 complications in total, 50 patients (47%) had complaints of hardware irritation, of which 34 (32%) had their hardware removed. Six patients (6%) needed refixation because of nonunion. CONCLUSION: We found beneficial outcomes in patients with UIS that underwent USO, although there was a large variance in the outcome and a relatively high number of complications (which includes plate removals). Results of this study may be used in preoperative counseling and shared decision-making when considering USO. LEVEL OF EVIDENCE: Therapeutic III.

On the Emergence Mechanism of Carrot Sprites.

We investigate the launch of negative upward streamers from sprite glows. This phenomenon is readily observed in high-speed observations of sprites and underlies the classification of sprites into carrot or column types. First, we describe how an attachment instability leads to a sharply defined region in the upper part of the streamer channel. This region has an enhanced electric field, low conductivity and strongly emits in the first positive system of molecular nitrogen. We identify it as the sprite glow. We then show how, in the most common configuration of a carrot sprite, several upward streamers emerge close to the lower boundary of the glow, where negative charge gets trapped and the lateral electric field is high enough. These streamers cut off the current flowing toward the glow and lead to the optical deactivation of the glow above. Finally, we discuss how our results naturally explain angel sprites.

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours.

PURPOSE: Therapy with [177Lu-DOTA,Tyr3]octreotate is effective in patients with grade I/II metastasized and/or inoperable bronchial neuroendocrine tumour (NET) or gastroenteropancreatic NET (GEP-NET). In this study, we investigated the efficacy and safety of salvage treatment with [177Lu-DOTA,Tyr3]octreotate. METHODS: Patients with progressive bronchial NET or GEP-NET were selected for re-(re)treatment if they had benefited from initial peptide receptor radionuclide therapy (I-PRRT) with a minimal progression-free survival (PFS) of 18 months. Patients received an additional cumulative dose of 14.8 GBq of [177Lu-DOTA,Tyr3]octreotate over two cycles per retreatment with PRRT (R-PRRT) or re-retreatment with PRRT (RR-PRRT). RESULTS: The safety and efficacy analyses included 181 patients and 168 patients, respectively, with bronchial NET or GEP-NET. Overall median follow-up was 88.6 months (95% CI 79.0-98.2). Median cumulative doses were 44.7 GBq (range 26.3-46.4 GBq) during R-PRRT (168 patients) and 59.7 GBq (range 55.2-≤60.5 GBq) during RR-PRRT (13 patients). Objective response and stable disease, as best response, were observed in 26 patients (15.5%) and 100 patients (59.5%) following R-PRRT, and in 5 patients (38.5%) and 7 patients (53.8%) following RR-PRRT, respectively. Median PFS was 14.6 months (95% CI 12.4-16.9) following R-PRRT and 14.2 months (95% CI 9.8-18.5) following RR-PRRT. Combined overall survival (OS) after I-PRRT plus R-PRRT and RR-PRRT was 80.8 months (95% CI 66.0-95.6). Grade III/IV bone marrow toxicity occurred in 6.6% and 7.7% of patients after R-PRRT and RR-PRRT, respectively. Salvage therapy resulted in a significantly longer OS in patients with bronchial NET, GEP-NET and midgut NET than in a nonrandomized control group. The total incidence of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) was 2.2%. No PRRT-related grade III/IV nephrotoxicity was observed. CONCLUSION: A cumulative dose of up to 60.5 GBq salvage PRRT with [177Lu-DOTA,Tyr3]octreotate is safe and effective in patients with progressive disease (relapse-PD) following I-PRRT with [177Lu-DOTA,Tyr3]octreotate. Safety appears similar to that of I-PRRT as no higher incidence of AML or MDS was observed. No grade III/IV renal toxicity occurred after retreatment.

Prenatal detection of an enteric duplication cyst.

Enteric duplication cysts are rare congenital malformations of unknown aetiology. Because of improvements in prenatal ultrasound, more and more duplication cysts are found prenatally and treatment is started early. We describe a case of enteric duplication cyst diagnosed prenatally and resected soon after birth. Early diagnosis and prompt surgical treatment are the best way to prevent associated morbidity.

Lutetium-labelled peptides for therapy of neuroendocrine tumours.

Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with (177)Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with (177)Lu-[DOTA(0),Tyr(3)]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with (177)Lu-DOTATATE as well as the limited side effects with additional cycles of (177)Lu-DOTATATE suggest that more cycles of (177)Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of (90)Y-[DOTA(0),Tyr(3)]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with (177)Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with (177)Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours.

Factors associated with return to work after open reinsertion of the triangular fibrocartilage.

The aim of this study was to assess return to work (RTW) after open Triangular Fibrocartilage Complex (TFCC) reinsertion. RTW after open surgery for TFCC injury was assessed by questionnaires at 6 weeks, 3 months, 6 months, and 12 months post-operatively. Median RTW time was assessed on inverted Kaplan-Meier curves and hazard ratios were calculated with Cox regression models. 310 patients with a mean age of 38 years were included. By 1 year, 91% of the patients had returned to work, at a median 12 weeks (25%-75%: 6-20 weeks). Light physical labor (HR 3.74) was associated with RTW within the first 15 weeks; this association altered from 23 weeks onward: light (HR 0.59) or moderate physical labor (HR 0.25) was associated with lower RTW rates. Patients with poorer preoperative Patient-Rated Wrist Evaluation (PRWE) total score returned to work later (HR 0.91 per 10 points). Overall cost of loss of productivity per patient was €13,588. In the first year after open TFCC reinsertion, 91% of the patients returned to work, including 50% within 12 weeks. Factors associated with RTW were age, gender, work intensity, and PRWE score at baseline.

Improved control of severe hypoglycemia in patients with malignant insulinomas by peptide receptor radionuclide therapy.

CONTEXT: Insulinomas are relatively rare neuroendocrine tumors of the pancreas. Only 10% are considered malignant. Control of insulin hypersecretion and hypoglycemia in patients with malignant insulinomas may be extremely difficult. Different medications and chemotherapy schedules have been used. PATIENTS: Five patients with metastatic insulinomas and severe, poorly controllable, hypoglycemia are described. These patients required continuous glucose infusion to control severe hypoglycemia, which were induced by the high levels of insulin secretion. Conventional medications, such as diazoxide, or streptozotocin-based chemotherapies had been used to control hypoglycemia but were ineffective and/or produced adverse effects. All patients were treated with sc octreotide. INTERVENTION: Peptide receptor radionuclide therapy with radiolabeled-somatostatin analogs was used. RESULTS: After the start of radiolabeled somatostatin analog therapy, the five patients with metastatic insulinomas had stable disease for a mean period of 27 months. During these months, the patients were without any hypoglycemic episodes. Finally, three of five patients died because of progressive disease. CONCLUSIONS: Radiolabeled somatostatin analog therapy can stabilize tumor growth and can be very successful in further controlling severe hypoglycemia in malignant insulinomas. In our series, this eventually resulted in improved survival outside the hospital setting.

Breath condenser coatings affect measurement of biomarkers in exhaled breath condensate.

Exhaled breath condensate collection is not yet standardised and biomarker measurements are often close to lower detection limits. In the current study, it was hypothesised that adhesive properties of different condenser coatings interfere with measurements of eicosanoids and proteins in breath condensate. In vitro, condensate was derived from a collection model using two test solutions (8-isoprostane and albumin) and five condenser coatings (silicone, glass, aluminium, polypropylene and Teflon). In vivo, condensate was collected using these five coatings and the EcoScreen condenser to measure 8-isoprostane, and three coatings (silicone, glass, EcoScreen) to measure albumin. In vitro, silicone and glass coatings had significantly higher albumin recovery compared with the other coatings. A similar trend was observed for 8-isoprostane recovery. In vivo, median (interquartile range) 8-isoprostane concentrations were significantly higher using silicone (9.2 (18.8) pg.mL(-1)) or glass (3.0 (4.5) pg.mL(-1)) coating, compared with aluminium (0.5 (2.4) pg.mL(-1)), polypropylene (0.5 (0.5) pg.mL(-1)), Teflon (0.5 (0.0) pg.mL(-1)), and EcoScreen (0.5 (2.0) pg.mL(-1)). Albumin in vivo was mainly detectable using glass coating. In conclusion, a condenser with silicone or glass coating is more efficient for measurement of 8-isoprostane or albumin in exhaled breath condensate, than EcoScreen, aluminium, polypropylene or Teflon. Guidelines for exhaled breath condensate standardisation should include the most valid condenser coating to measure a specific biomarker.

Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT?

PURPOSE: Patients with somatostatin receptor subtype 2-positive metastasised neuroendocrine tumours can be treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate. Some use octreotide as the peptide for peptide receptor radionuclide therapy (PRRT). We compared in seven patients [(177)Lu-DOTA(0),Tyr(3)]octreotide ((177)Lu-DOTATOC) and [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE), to see which peptide should be preferred for PRRT with (177)Lu. METHODS: In the same patients, 3,700 MBq (177)Lu-DOTATOC and 3,700 MBq (177)Lu-DOTATATE was administered in separate therapy sessions. Amino acids were co-administered. Whole-body scanning was performed on days 1, 4 and 7 post therapy. Blood and urine samples were collected. We calculated residence times for tumours, spleen and kidneys. RESULTS: All patients had longer residence times in spleen, kidneys and tumours after use of (177)Lu-DOTATATE (p=0.016 in each case). Comparing (177)Lu-DOTATATE with (177)Lu-DOTATOC, the mean residence time ratio was 2.1 for tumour, 1.5 for spleen and 1.4 for kidneys. Dose-limiting factors for PRRT are bone marrow and/or kidney dose. Although the residence time for kidneys was longer when using (177)Lu-DOTATATE, the mean administered dose to tumours would still be advantageous by a factor of 1.5, assuming a fixed maximum kidney dose is reached. Plasma radioactivity after (177)Lu-DOTATATE was comparable to that after (177)Lu-DOTATOC. Urinary excretion of radioactivity was comparable during the first 6 h; thereafter there was a significant advantage for (177)Lu-DOTATOC. CONCLUSION: (177)Lu-DOTATATE had a longer tumour residence time than (177)Lu-DOTATOC. Despite a longer residence time in kidneys after (177)Lu-DOTATATE, tumour dose will always be higher. Therefore, we conclude that the better peptide for PRRT is octreotate.

Molecular radiotherapy with somatostatin analogs for (neuro-)endocrine tumors.

Peptide receptor radionuclide therapy (PRRT) holds great promise for the future regarding the treatment of various cancers. With the use of radiolabelled peptides, which bind with high affinity to their receptors on cancer cells, it is possible to target the cancer efficiently. In gastroenteropancreatic tumors, radiolabelled somatostatin analog therapy has proven to be effective. Dose-limiting organs are the bone marrow and the kidneys. With the currently used dose schemes and kidney protection, PRRT is relatively safe and serious side-effecs are rare. Which radiolabelled somatostatin analog can be regarded as the most effective therapy cannot be concluded from the available literature. Also, the development of therapy strategies with combinations of different radionuclides and or peptides is of interest as these strategies may provide an increase in therapeutic efficacy in the future.

Physical effects of biologically formed cholesterol oxidation products on lipid membranes investigated with fluorescence depolarization spectroscopy and electron spin resonance.

Planar oriented membranes of 1-palmitoyl, 2-oleoyl-phosphatidylcholine (POPC) containing cholesterol, 19-hydroxycholesterol, 22S-hydroxycholesterol, or 25-hydroxycholesterol in concentrations up to 5 mol % were investigated with angle-resolved fluorescence depolarization and electron spin resonance measurements. Analyses of the data with the Brownian diffusion model show that the oxysterols have structural effects similar to those of cholesterol: an increase in molecular order and no change in the rotational diffusion coefficients of the probe molecules. Time-resolved fluorescence anisotropy measurements on diphenylhexatriene (DPH) in small unilamellar vesicles of POPC and DOPC were performed using oxysterols commonly found in oxidized low density lipoproteins (LDL) in comparison to membranes containing cholesterol or no sterols. Analyses using the Brownian rotational diffusion model show that most LDL-oxysterols affect the vesicle physical structure in a manner similar to cholesterol, viz. an increase in molecular order and a decrease in the dynamics. Cholesterol-alpha-epoxide has a much smaller ordering effect than cholesterol in POPC-vesicles. A similar effect was found for 7 beta-hydroxycholesterol in DOPC-vesicles. The tendency of the oxysterols to influence the molecular order as compared to pure cholesterol may contribute to cell membrane permeability changes affecting crucial cell functions and events leading to vascular cell injury. Increased LDL oxysterol levels may account for some of the structural changes noted for oxidatively modified LDL as well as its toxicity to vascular cells.

Influence of litter size and breed on the duration of gestation in dogs.

The variation in the duration of gestation, defined as the period from mating to parturition, was studied in 113 bitches of six breeds (31 Dobermans, 31 Labrador retrievers, 14 German shepherds, 13 Bernese mountain dogs, 12 golden retrievers and 12 West Highland white terriers). The bitches were mated once on the optimal day for mating, which was established by measuring the plasma concentration of progesterone. The duration of gestation varied between 58 and 65 days with a mean of 61.4 +/- 1.5 days (+/- SD). The mean duration of gestation in West Highland white terriers (62.8 +/- 1.2 days) was significantly longer than that of German shepherds (60.4 +/- 1.7; P < 0.001), Labrador retrievers (60.9 +/- 1.5; P < 0.001) and Dobermans (61.4 +/- 1.0; P < 0.025). The variation in the duration of gestation in any one of the six breeds was low, ranging from 4 to 7 days, or less when litters of one pup (n = 4) were excluded. The number of pups per litter varied between one and 15 with a median of eight pups. In the total population, the duration of gestation was negatively correlated with litter size (r = -0.73; P = 0.005) for litters (n = 112) containing < or = 13 pups. However, within each breed multiple regression analysis failed to show any influence of litter size on the duration of gestation. The median litter size of different breeds and the mean duration of gestation were negatively correlated (r = -0.78; P = 0.03; n = 6). Therefore, although it was not conclusively proven, the results indicate that the breed is a major determinant of the duration of gestation in bitches and that the influence of breed may be ascribed to breed-related differences in litter size.

Kinetics of recovery of serum Ig levels and of cytoplasmic Ig positive cells in various lymphoid organs of nude mice after thymus transplantation.

The long-term effects of thymus transplantation in nude mice were studied with regard to the number of cytoplasmic immunoglobulin positive plasmablasts and plasma cells (C-Ig cells) in various lymphoid organ and their immunoglobulin (Ig) class distribution profile. These data were correlated with the serum Ig levels of the same mice. Four weeks after thymus transplantation, the number of C-Ig cells in the spleen of nude mice had increased two- to three-fold over that found in normal nude mice and normal heterozygous littermates of the same age. This overshoot subsided at 8 weeks after thymus transplantation. The increase of the C-Ig cell number in the other lymphoid organs tested (bone marrow, mesenteric lymph nodes and Peyer's patches) started later than in spleen, and did not show a clear overshoot. Almost complete recovery of the C-Ig cell pattern to that of normal littermates was found 32 weeks post-transplantation. Analysis of the Ig class distribution of the C-Ig cells showed that the increase of the C-Ig cell numbers after thymus transplantation in nude mice was almost exclusively confined to IgG1, IgG2 and IgA. The increase of C-IgG1 and C-IgG2 cells in spleen and bone marrow correlated with a simultaneous increase of the serum IgG1 and IgG2 levels, suggesting that these organs are the major source of serum IgG in young adult mice.

The distribution of cytoplasmic immunoglobulin containing cells over various lymphoid organs of congenitally athymic (nude) mice as a function of age.

The distribution of cells containing cytoplasmic immunoglobulin (C-Ig cells) over various lymphoid organs was studied in congenitally athymic (nude) mice as a function of age. The C-IgM, C-IgG and C-IgA cells were enumerated in spleen, bone marrow, mesenteric lymph node and Peyer's patches of nude mice and their heterozygous littermates of 6, 40 and 100 weeks of age. In the nude as well as in the heterozygous mice an age-related shift was observed in the localization of the C-Ig cells. In young mice of both groups the majority of these cells resided in the spleen, whereas in adult and old mice the bone marrow was found to be the major C-Ig cell organ, indicating that this shift is not dependent on the presence of the thymus. In young and adult nude and heterozygous mice C-Ig cell numbers in the spleen were comparable, whereas C-Ig cell numbers in the other lymphoid organs were higher in the heterozygous mice than in the nude mice. The total C-Ig cell number in young and adult nude mice was lower than in heterozygous mice of the same age, whereas in old nude mice they were as high as in heterozygous mice of the same age, indicating a retarded development of the immunological activity in nude mice. C-Ig cells in nude mice were almost exclusively of the IgM class, although in the bone marrow of the oldest animals also a substantial number of C-IgG and C-IgA cells was observed. Our finding that nude mice can live up to at least two years of age indicates that the age-related deterioration of the thymus-dependent limb of the immune system is not the cause of ageing, but rather a consequence of it.

Expression of the activation antigen CD27 in rheumatoid arthritis.

Differentiation of CD4+ T-cells is reflected by the change from the CD45RA+CD27+ phenotype via CD45RO+CD27+ to the CD45RO+CD27- phenotype. To provide insight into the migration and activation of T-cells at the site of inflammation in rheumatoid arthritis (RA), CD27 expression by T-cells in peripheral blood (PB), synovial fluid (SF), and synovial tissue (ST) as well as the levels of the soluble form of CD27 (sCD27) in plasma and SF were studied in patients with RA. Since CD4+CD27+ T-cells are involved in providing helper activity for B-cells, we also investigated the levels of rheumatoid factors in serum and SF in relation to CD27 expression. The mean level of sCD27, which is produced by CD27+ cells, and the mean percentage of CD27 T-cells within the CD4+CD45RA- subset were higher in SF than in PB. SF sCD27 levels were higher in the patients with RA than in the patients with osteoarthritis, who served as controls. In ST infiltration by CD4+CD45RO+CD27+ T-cells, could be demonstrated in the rheumatoid perivascular lymphocytic aggregates with a relative increase in the percentage of CD27- T-cells in the diffuse lymphocytic infiltrate. The sCD27 levels and the percentages of CD4+CD27+ cells in SF correlated positively with the levels of rheumatoid factors in serum and SF. The findings presented in this study suggest a continuous influx of preactivated CD4+CD45RO+CD27+ cells from the PB into the rheumatoid ST and further activation and differentiation to CD4+CD45RO+CD27- cells in situ, followed by migration to the SF. These activated T-cells are likely to play a role in synovial inflammation.

Regulation of the "spontaneous' (background) immunoglobulin synthesis.

The number of mature cytoplasmic immunoglobulin containing cells (C-Ig cells) in various lymphoid organs of the mouse was studied as a function of antigenic load and the presence of T cells. Both antigen and T-cell deprivation decreased the number of C-Ig cells (plasma blasts and plasma cells). The absolute C-Ig cell numbers were minimal in germfree nude mice, intermediate in specific pathogen-free (SPF) nude mice and in germ-free thymus-bearing mice, and the largest in SPF thymus-bearing mice. The bone marrow was the organ where this picture was most strikingly examplified. In germfree C3H mice raised on a synthetic diet the bone marrow of 3 out of 4 mice tested did not show any C-Ig cell. None of them had C-Ig cells in the mesenteric lymph nodes. The Ig class distribution of the C-Ig cells and the incidence of C-Ig cells positive for more than one Ig heavy-chain isotype ("double producers') were also highly dependent upon the antigenic load and the presence of T cells. C-IgM cells were well represented in all groups of mice. Appreciable numbers of C-IgA cells were only found in SPF thymus-bearing mice. The absolute number, but not the relative number, of C-IgG cells followed the same pattern. The percentages of double producers in the various lymphoid organs were largest in germfree nude mice, intermediate in SPF nude mice and in germfree thymus-bearing mice, and minimal in SPF thymus-bearing mice. From these studies we conclude that the background synthesis of IgG and IgA in not intentionally immunized mice is virtually completely dependent on stimulation of the immune system by external antigens, in contrast to the production of IgM.