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PubMed2001

Predictors of persistence of use of the novel antidiabetic agent acarbose.

BACKGROUND: A carbose is the first of a new class of antidiabetic agents, the alpha-glucosidase inhibitors. This study characterizes and identifies predictors of persistence of use of acarbose. METHODS: Medical, pharmaceutical, and demographic records were extracted for 2 cohorts of patients (social assistance recipients and seniors) from the databases of Quebec's provincial health plan. Patients were eligible for inclusion if they had received their first dispensation of acarbose between August 1, 1996, and December 31, 1997. The observation period included at least 1 year before the first dispensation and a minimum of 4 months after. RESULTS: New users of acarbose included 216 social assistance recipients and 677 seniors who were followed up for 82 914 and 270 041 person-days, respectively. Median persistence with acarbose treatment was 83 days (95% confidence interval, 75-105 days) for social assistance recipients and 105 days (95% confidence interval, 90-119 days) for seniors. In both cohorts, treatment by an endocrinologist vs another physician predicted longer treatment persistence. In the seniors cohort, additional determinants of (earlier) treatment discontinuation included a higher initial daily dose, previous treatment with insulin, and consultation with a gastroenterologist after treatment initiation. CONCLUSIONS: New users of acarbose showed low persistence in 2 cohorts of beneficiaries of Quebec's provincial health plan. Prescribing specialist was an important predictor of persistence in seniors and the socially assisted. The importance of 4 additional factors in seniors only led to hypotheses concerning population differences in treatment expectations and in the occurrence and tolerance of adverse effects.

Acarbose↗
PubMed1992

Persistent worsening of stroke sequelae after delayed seizures.

Though the role of cerebral ischemia as an etiologic factor for epilepsy is accepted, the effect of seizures on stroke sequelae has received little attention. We describe 10 patients with poststroke partial epileptic seizures that were followed by persistent worsening of the previous neurologic deficit. Of 38 other patients with poststroke seizures who were examined during the same period, eight suffered transient neurologic worsening (Todd's phenomenon). Persistent worsening was associated with longer seizures and longer partial seizures before generalization. Risk factors, age, sex, other seizure features, and characteristics of previous stroke were irrelevant to developing persistent worsening of stroke sequelae. None of the patients with persistent worsening showed a new lesion or an extension of the previous ischemic area on computed tomography or magnetic resonance imaging, except one who had a first hemorrhage that spared the cortex and who suffered a second hemorrhage, which was lobar. Persistent worsening of a neurologic deficit following a seizure in patients with previous stroke may not be uncommon and may be due to a direct effect of the seizure itself on the infarcted area.

Adult↗
PubMed1999

Prognostic factors for persistent otitis media with effusion in infants.

OBJECTIVE: To study prognostic factors for persistent otitis media with effusion (OME) in a birth cohort of 30,099 children born in the eastern part of The Netherlands between January 1, 1996, and April 1, 1997. DESIGN: Case-referent study. SUBJECTS: Children who failed a triple hearing test before their first birthday and were subsequently diagnosed with bilateral OME during 3 of the 4 bimonthly visits to an ear, nose, and throat (ENT) department (n = 372). The persistent cases were compared with 3 referent groups: (1) all the children who attended the first of 3 hearing tests; (2) all the children of the birth cohort who were referred to an ENT department after the third hearing test; and (3) all the children who were diagnosed with bilateral OME during the first visit to an ENT department. RESULTS: When all the children who participated in the first hearing test were taken as referents, persistent OME was associated with upper respiratory tract infections, attending a day-care center, having older siblings, and a family history of otitis media. When all the children who were referred to an ENT department were taken as referents, only attending a day-care center was associated with persistent OME. When the children diagnosed with bilateral OME during the first visit to an ENT department were taken as referents, no prognostic factors were found for OME persistence. CONCLUSION: When a child is referred early, an otolaryngologist can ask the parent about the presence of prognostic factors to decide which policy to follow.

Case-Control Studies↗
PubMed2002

Persistent parathyroid hormone elevation following curative parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: Persistent elevation of parathyroid hormone (PTH) levels following parathyroidectomy may indicate residual abnormal parathyroid tissue. OBJECTIVE: To determine the clinical significance and risk factors for persistent PTH elevation following curative parathyroidectomy. METHODS: A prospective study of consecutive patients with primary hyperparathyroidism who had resolution of hypercalcemia following parathyroidectomy. Patients with low or normal serum calcium and increased PTH levels postoperatively were identified, and serial calcium and PTH levels and clinical course were monitored. A multivariate analysis was performed to identify features associated with an elevated postoperative PTH level. RESULTS: Of 85 patients with resolution of hypercalcemia following parathyroidectomy, postoperative PTH levels were elevated in 23 (27%) (mean, 99 pg/mL; range, 70-194 pg/mL) and normal in 62 (mean, 30 pg/mL; range, 3-65 pg/mL) (P<.001). No significant differences in preoperative or postoperative calcium or preoperative PTH levels were found between groups. Among patients with persistent PTH elevation, 18 had adenoma and 5 had multiglandular disease, compared with 52 with adenoma and 10 with multiglandular disease in patients with normal postoperative PTH levels (P>.05). Multivariate analysis demonstrated that black race and musculoskeletal symptoms were associated with an elevated postoperative PTH level (P =.01. After an average 16-month follow-up, PTH levels normalized in 13 patients, decreased in 5, and were unchanged in 2. Three patients were lost to follow-up. CONCLUSIONS: Persistent PTH elevation occurs in 27% of patients following curative parathyroidectomy and is usually a transient phenomenon more common in patients with musculoskeletal symptoms and of the black race. It is not a manifestation of persistent disease but is most likely a secondary response to bone remineralization.

Adult↗
PubMed2004

Persistent vertigo following particle repositioning maneuvers: an analysis of causes.

OBJECTIVE: To analyze the causes of persistent vertigo following treatment with particle repositioning maneuvers (PRMs) in patients with benign paroxysmal positional vertigo. DESIGN: Prospective study of outcomes in patients with benign paroxysmal positional vertigo. STUDY SETTING: Outpatient clinic of a tertiary care referral center. PATIENTS: A sample of 90 consecutive patients with documented benign paroxysmal positional vertigo of the posterior semicircular canal who had persistent vertigo after at least 3 sessions of PRMs during a period of 2 weeks. INTERVENTION: Particle repositioning using a modified Epley maneuver. MAIN OUTCOME MEASURE: Persistent vertigo following at least 3 sessions of PRMs over a period of 2 weeks. RESULTS: Seven patients showed partial or no improvement following treatment. The causes subsequently determined included coincident horizontal canal positional vertigo (2 cases), Ménière's disease (2 cases), persistent posterior canal benign paroxysmal positional vertigo in association with cervical spondylosis (2 cases), and a posterior fossa meningioma (1 case). CONCLUSIONS: Patients with persistent or frequently recurring positional vertigo following treatment with PRMs should undergo detailed investigation to exclude coincidental pathology for which specific treatment is required. In patients in whom no coincident pathology requiring therapy is identified, treatment options other than the PRM already instituted should be considered.

Aged↗
PubMed1992

The persistent parent.

Parental persistence in the diagnosis and treatment of a child's illness can be examined by asking whether it is congruent with the child's morbidity. The relationship between parental persistence and child morbidity always depends on a "first diagnosis" (ie, what is wrong with the child, if anything?). In many instances, a "second diagnosis" (ie, why is the child being brought to you at this time?) should not be overlooked. First and second diagnoses are identical if persistence and morbidity are congruent but are different if they are incongruent. Once incongruent persistence is suspected, the possibility of parental falsification of symptoms must be faced. In patients in whom a second diagnosis must be made, the second diagnosis may be as simple as maternal anxiety or as complex as Munchausen syndrome by proxy. A "persistence algorithm" is presented and illustrated by descriptions of four children referred to a pulmonologist with complaints suggestive of respiratory disease. The approach, as outlined in the algorithm, may have broad pediatric applications.

Child↗
PubMed2000

Low salivary cortisol and persistent aggression in boys referred for disruptive behavior.

BACKGROUND: Persistent antisocial behavior in adulthood is often preceded by childhood-onset aggressive conduct disorder. Aggressive syndromes in both children and adults have previously been associated with abnormalities in peripheral responses to stress. One peripheral measure, salivary cortisol concentration, may reflect individual differences in the hypothalamic-pituitary-adrenal axis that underlie propensities for aggression, socialization, and adaptation to stress. METHODS: The relationship between salivary cortisol levels and aggression was tested in 38 clinic-referred school-aged boys. Persistent aggression was measured by collecting disruptive behavior disorder symptoms in 4 annual clinical evaluations and peer nominations of aggression in the first 2 annual evaluations. Salivary cortisol levels were measured during years 2 and 4 of the study. RESULTS: Low cortisol levels were associated with persistence and early onset of aggression, particularly when measures of cortisol concentrations were pooled. Boys with low cortisol concentrations at both time points exhibited triple the number of aggressive symptoms and were named as most aggressive by peers 3 times as often as boys who had higher cortisol concentrations at either sampling time. CONCLUSIONS: This suggests that low hypothalamic-pituitary-adrenal axis activity is a correlate of severe and persistent aggression in male children and adolescents. A restricted (low) range of cortisol variability may be more indicative of persistent aggression than a low concentration of cortisol at any single point in time.

Adult↗
PubMed2001

Parental and early childhood predictors of persistent physical aggression in boys from kindergarten to high school.

BACKGROUND: In a prior study, we identified 4 groups following distinct developmental courses, or trajectories, of physical aggression in 1037 boys from 6 to 15 years of age in a high-risk population sample from Montréal, Québec. Two were trajectories of high aggression, a persistently high group and a high but declining group. The other 2 trajectories were a low group and a moderate declining group. This study identified early predictors of physical aggression trajectories from ages 6 to 15 years. METHODS: In this study, logistic regression analysis was used to identify parental and child characteristics that distinguished trajectory group membership. RESULTS: For boys displaying high hyperactivity and high opposition in kindergarten, the odds of membership in the 2 high aggression groups were increased by factors of 3.0 (95% confidence interval [CI], 2.0-4.3) and 2.7 (95% CI, 1.9-3.8), respectively, compared with boys without these risks. Counterpart odds ratios for the risk factors of mothers' teen-onset of parenthood and low educational attainment were 1.6 (95% CI, 1.1-2.2) and 1.8 (95% CI, 1.3-2.4), respectively. Only the maternal characteristics distinguished between the trajectory of persistently physical high aggression and the trajectory starting high but subsequently declining. For the 2 maternal risk factors combined, the odds ratio of persisting in high level physical aggression was 9.4 (95% CI, 2.9-30.4). CONCLUSIONS: Kindergarten boys displaying high levels of opposition and hyperactivity are at high risk of persistent physical aggression. However, among kindergarten boys who display high levels of physical aggression, only mothers' low educational level and teenage onset of childbearing distinguish those who persist in high levels of physical aggression.

Adolescent↗
PubMed1998

Persistence of use of lipid-lowering medications: a cross-national study.

CONTEXT: Although clinical trials have demonstrated the benefits of lipid-lowering therapy, little is known about how these drugs are prescribed or used in the general population. OBJECTIVE: To estimate predictors of persistence with therapy for lipid-lowering drug regimens in typical populations of patients in the United States and Canada. DESIGN: A cohort study defining all prescriptions filled for lipid-lowering drugs during 1 year, as well as patients' demographic and clinical characteristics. SETTING: New Jersey's Medicaid and Pharmacy Assistance for the Aged and Disabled programs and Quebec's provincial medical care program. PATIENTS: All continuously enrolled patients older than 65 years who filled 1 or more prescriptions for lipid-lowering drugs (N = 5611 in the US programs, and N = 1676 drawn from a 10% sample in Quebec). MAIN OUTCOME MEASURES: Proportion of days during the study year for which patients had filled prescriptions for lipid-lowering drugs; predictors of good vs poor persistence with therapy. RESULTS: In both populations, patients failed to fill prescriptions for lipid-lowering drugs for about 40% of the study year. Persistence rates with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors were significantly higher than those seen with cholestyramine (64.3% vs 36.6% of days with drug available, respectively). Patients with hypertension, diabetes, or coronary artery disease had significantly higher rates of persistence with lipid-lowering regimens. In New Jersey, multivariable analysis indicated that the poorest patients (those enrolled in Medicaid) had lower rates of drug use than less indigent patients (those enrolled in Pharmacy Assistance for the Aged and Disabled) after adjusting for possible confounders, despite virtually complete drug coverage in both programs. When rates of use were measured in the US population for the 5 years following the study year, only 52% of surviving patients who were initially prescribed lipid-lowering drugs were still filling prescriptions for this drug class. CONCLUSION: In all populations studied, patients who were prescribed lipid-lowering drug regimens remained without filled prescriptions for over a third of the study year on average. Rates of persistence varied substantially with choice of agent prescribed, comorbidity, and socioeconomic status, despite universal coverage of prescription drug costs. After 5 years, about half of the surviving original cohort in the United States had stopped using lipid-lowering therapy altogether.

Aged↗
PubMed1996

Human papillomavirus genotype as a predictor of persistence and development of high-grade lesions in women with minor cervical abnormalities.

Women referred for colposcopy with mild and moderate dyskaryosis and found to have only minor cervical abnormalities were screened for oncogenic human papilloma virus (HPV) types. The natural development of these abnormalities in 42 HPV-positive women was assessed by cytology and colposcopy at 6-month intervals for up to 2 years. As is the case with cancers and high-grade cervical intra-epithelial neoplasia (CIN), minor cervical abnormalities were frequently found to be associated with HPV16, -18, -31 and -33. Viral persistence and the development of high-grade lesions were found to be closely associated with HPV16; 56% of HPV16 isolates were persistent compared to 7% of other HPV types, and all 4 subsequent CIN 3 lesions were in women with persistent infection. A striking association of persistence with a variant of HPV16 having a base change at nucleotide 350 was observed. Ten of 12 women with this variant had persistent infection compared to only 1 of 16 women infected with the HPV16 prototype.

Adult↗
PubMed1999

Stereotactic radiosurgery as a salvage treatment for locally persistent and recurrent nasopharyngeal carcinoma.

BACKGROUND: The purpose of this work was to study the efficacy of stereotactic radiosurgery as a salvage treatment in patients with locally persistent and recurrent nasopharyngeal carcinoma (NPC). METHODS: Between March 1996 and August 1997, 10 patients with locally persistent or recurrent NPC were treated by linac-based stereotactic radiosurgery. Four patients had radiosurgery for persistent disease after a first course of radiotherapy, 3 had radiosurgery as a boost after reirradiation for local recurrence, and 3 had radiosurgery for disease that recurred after reirradiation. The tumor volume ranged from 1.3 to 23.7 cc (median: 5.2). Treatment was prescribed at 80% isodose line and ranged from 12 to 18 Gy (median: 13.4), with a mean tumor surface dose ranged from 10-21 Gy (median: 14). The median clinical follow-up was 10.5 months (range 8-27), and the median imaging follow-up was 9.5 months (range 6-26). RESULTS: One patient had complete regression of tumor after radiosurgery, five had reduction in tumor size, three had no change, and one had progression of tumor. The overall response rate to radiosurgery was 60% (6/10), with 10% (1/10) developing in-field progression. Excluding patients receiving radiosurgery as a boost treatment after reirradiation, the response rate was 57% (4/7) and none developed in-field progression. Only one patient developed a new cranial neuropathy in the absence of disease progression. CONCLUSION: In selected patients with locally persistent or recurrent NPC, stereotactic radiosurgery can be considered as a salvage treatment with good short-term local control. The complications appear to be minimal except for treating recurrence in the cavernous sinus. Early results are encouraging although more experience and longer follow-up are still needed to better define the role of radiosurgery in the management of persistent and recurrent NPC.

Adenocarcinoma↗
PubMed2000

Can persisting detrusor hyperreflexia be predicted after transurethral prostatectomy for benign prostatic hypertrophy?

Detrusor hyperreflexia (DH) is frequently found in patients with benign prostatic hypertrophy (BPH) and persists in 30-50% of patients after successful removal of bladder neck obstruction by transurethral prostatectomy (TUR-P) or surgical enucleation of the prostate. It would be beneficial for surgeons to be able to identify patients who are at risk of persistent post-operative urinary irritation symptoms and DH. Twenty-three patients who showed DH pre-operatively were included in this study. Of these 23 patients, four had neurogenic bladder because of previous cerebrovascular disease. The other 19 patients were considered to have DH because of BPH. These 19 patients were classified according to their cystometry chart patterns. Pattern 1 was the continual sporadic onset and offset of DH, pattern 2 was a single episode of DH at a bladder volume of <160 mL, and pattern 3 was a single DH episode at a bladder volume >160 mL. Preoperative single-photon emission computed tomography (SPECT) was performed on 14 patients. Cystometric findings at 3 to 6 months after surgery were compared with the pre-operative findings. Four of the six patients with pattern 2 (67%) and all patients with pattern 3 (100%) showed an absence of DH after surgery. In contrast, all five patients with pattern 1 and all four patients with neurogenic bladder showed persistent DH. Compared with pattern 3 patients, pattern 1 patients more frequently complained of urgency before surgery, and their symptoms and uroflowmetry parameters did not improve afterward. Among 14 patients who had pre-operative SPECT, all eight patients with low cerebral blood flow in the frontal region showed persisting DH. Conversely, all six patients with normal SPECT results showed no DH after surgery. When DH occurs repeatedly (pattern 1) or occurs at a bladder volume of <160 mL (pattern 2), there is a greater risk of post-operative irritation symptoms. Abnormal SPECT findings can also predict the post-operative persistence of DH. Combing these two pre-operative examinations allows us to predict better post-operative DH in patients with BPH.

Aged↗
PubMed1999

Persistence of mild, early inflammatory arthritis: the importance of disease duration, rheumatoid factor, and the shared epitope.

OBJECTIVE: To determine the factors that predict clinical outcome at 6 months for patients with mild, early inflammatory arthritis. METHODS: Sixty-three patients with mild, untreated, early arthritis were given a single dose of corticosteroids at presentation. Administration was intramuscular if disease was polyarticular (n = 53) or intraarticular if patients had <5 synovitic joints (n = 10). The primary outcome measure was clinical disease remission or persistence of arthritis at 6 months following injection. RESULTS: At 6 months following injection, 49 of the 63 patients (78%) had persistent inflammatory joint disease. The other 14 (22%) had clinical disease remission. Regression analysis showed that only disease duration was significantly associated with persistent arthritis (P < 0.05). The other significant factor (by chi-square test) was the presence of the shared epitope (SE). Of the patients fulfilling the American College of Rheumatology (ACR) criteria at presentation (51% of the total), 53% with disease duration of < or = 12 weeks at presentation had persistent disease 6 months later, compared with 94% of those who presented with disease duration of >12 weeks. CONCLUSION: The strongest predictor of persistent disease was a disease duration of >12 weeks. Rheumatoid factor and SE were also predictors to a lesser extent. Patients who both fulfilled the ACR classification criteria for rheumatoid arthritis (RA) and had a short disease duration included some with an excellent prognosis. Therefore, 12 weeks may be a more appropriate disease duration to use for the RA classification criteria. Administering a bolus of corticosteroids may be a useful diagnostic/therapeutic approach.

Adrenal Cortex Hormones↗
PubMed1983

The reasons for persistent hypercalcaemia after cervical exploration for presumed primary hyperparathyroidism.

Of 500 consecutive patients who underwent cervical exploration for presumed primary hyperparathyroidism, 461 (92.2 per cent) were cured, as judged by an immediate return of serum calcium levels to normal. Thirty-nine patients (7.8 per cent) had persistent hypercalcaemia after the initial operation. The clinical profiles, operative and pathologic findings, surgical procedures performed and subsequent management of these 39 patients were reviewed. At reevaluation, 4 patients were noted to have been cured of their hyperparathyroidism. Twenty-one patients had persistent hyperparathyroidism: in 6, all 4 parathyroid glands had not been identified at the initial operation and in 15, hypercalcaemia persisted after the identification of 4 glands. One patient had recurrent hyperparathyroidism after the removal of a 720 mg adenoma and the identification of 3 normal parathyroid glands. Nine patients had nonparathyroid causes for the hypercalcaemia: 2 had occult malignant neoplasms, 6 had benign familial hypocalciuric hypercalcaemia and 1 had immobilization hypercalcaemia. In 4 patients the reason for the persistent hypercalcaemia remained unclear. We suggest a schema that may be used as a guideline in the investigation and management of patients with persistent hypercalcaemia after primary neck exploration for presumed hyperparathyroidism.

Adenoma↗
PubMed1995

Primitive persistent carotid-basilar and carotid-vertebral anastomoses: a report of seven cases and a review of the literature.

The persistence of embryonic carotid-basilar and carotid-vertebral anastomoses was investigated retrospectively in 4,400 cerebral angiograms. Six primitive persistent carotid-basilar anastomoses and one primitive persistent carotid-vertebral anastomosis were found. In 4,400 cerebral angiograms, the incidence of primitive carotid-basilar and carotid-vertebral anastomoses was 0.14% and 0.023% respectively. Primitive persistent anastomoses are associated with intracranial vascular anomalies, especially aneurysms. The clinical and pathological findings in combination with these primitive persistent anastomoses were also examined.

Adult↗
PubMed2005

The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence.

BACKGROUND: The prognostic significance of isolated tumor cells (ITCs) in bone marrow (BM) from patients with breast carcinoma at the time of their primary diagnosis recently was been confirmed by a large pooled analysis. If the persistence of ITCs after adjuvant therapy confers a similar risk for recurrence, then it would be an indication to consider secondary adjuvant therapy. METHODS: The authors analyzed BM aspirates from 228 patients during recurrence-free follow-up at a median interval +/- standard deviation (SD) of 21.3 +/- 29.1 months after a primary diagnosis of breast carcinoma (pathologic T1 [pT1]-pT2, pN0-pN3, pM0). Carcinoma cells were detected using a standardized immunoassay with monoclonal antibody A45-B/B3 directed against cytokeratin (CK). Patients were followed for a median +/- SD of 49.8 +/- 32.1 months after their primary diagnosis. RESULTS: Persistent ITCs in BM were detected in 12.7% of patients (n=29 patients). Positive BM status was more frequent (15.7%) within the first 21 months after primary diagnosis than after a follow-up > 21 months (9.7%). The Kaplan-Meier estimate for mean recurrence-free survival was 149.7 months (95% confidence interval [95% CI], 139.6-159.8 months) in patients with negative BM status and 86.5 months (95% CI, 65.7-107.4 months; P=0.0003) in patients with positive BM status at the time patients underwent follow-up BM aspiration. Patients who were without evidence of persistent ITCs had a significantly longer overall survival (162.1 months; 95% CI, 152.1-172.0 months) compared with patients who had positive BM status (overall survival, 98.7 months; 95% CI, 79.7-117.9 months; P=0.0008). In multivariate Cox regression analysis that included BM status, tumor size, lymph node status, and histopathologic grade, evidence of ITCs was an independent significant predictor for reduced disease-free survival (relative risk [RR], 4.57; P <0.0001) and overall survival (RR, 5.57; P=0.002). Persistent ITCs had the greatest prognostic relevance when they were detected between 25 months and 42 months after primary diagnosis (RR, 7.68). CONCLUSIONS: Evidence of persistent ITCs in BM from patients with breast carcinoma indicated an increased risk for subsequent recurrence. Prospective trials should investigate the benefit of secondary adjuvant treatment on the basis of BM marrow status.

Bone Marrow↗
PubMed1990

Reorganization of persistent motoneurons in a metamorphosing insect (Tenebrio molitor L., Coleoptera).

The present analysis outlines how the shape of motoneurons which persist through metamorphosis in the beetle Tenebrio molitor is regulated by cellular interactions. This study focused on the structural changes of prothoracic leg motoneurons. The fate of these neurons is described in normal metamorphic development, so as to provide a basis for experimental analysis. In a first experiment the prothoracic leg imaginal discs or part of these were extirpated in the prepupa or early pupa. In a second experiment the leg imaginal discs were rotated by 180 degrees in early larval instars of Tenebrio; the procedure caused a threefold leg anlage. Thereafter, the treated individuals continued to develop. In both experiments the effect of the operation on the structure of the dendritic trees of the persisting motoneurons was analyzed at the imaginal stage. In the first experiment the dendritic tree of the motoneurons is locally deleted. In the second experiment the branching index (quantitative description of dendritic arborization pattern) of the dendritic tree of the persisting motoneurons increased. Both experiments provided evidence that the shape of persistent leg motoneurons is stabilized and even regulated by cellular interactions during metamorphosis. Evidence is presented that sensory neurons are effective both in stabilization and regulation of the shape of persistent motoneurons.

Amputation, Surgical↗
PubMed1991

Clonal persistence of B lymphocytes in normal mice is determined by variable region-dependent selection.

Many adult splenic B cells die within 1 week in the spleen of adoptive adult recipient mice; in contrast, the cellular environment of newborn recipients allows for their expansion and persistence for several weeks. In the present study, we show that the local environment of adult peritoneal cavity also allows adult splenic B cells to persist for over 2 weeks after intraperitoneal transfer. In order to determine whether the persistence of donor B cells in newborn hosts and in the peritoneum of adult recipients results from a selection process involving the clonal specificities expressed, the variation in time of VH gene family repertoires of donor B cells was analyzed in the hosts. At different times after the transfer of splenic cells from lipopolysaccharide (LPS)-reactive mice into LPS-non responder histocompatible recipients, mRNA colony blot assays were performed. The results show that among the donor adult LPS-reactive B cells, the VH genes are differently used by the expanding or persisting B cells, in both kinds of recipients. Thus, cells expressing J558 or VH11 gene families are, in particular, positively selected, while those expressing D-proximal or J606 and 36-30 VH gene families are less selected. These findings demonstrate that the propensity of B cells to persist and expand is determined by their selection through their immunoglobulin variable regions, rather than by genetic properties linked to particular B cell subsets.

Animals↗