Population preference for treatment of uncomplicated appendicitis.

BACKGROUND: Non-operative treatment of uncomplicated appendicitis is safe and increasing in popularity, but has other risks and benefits compared with appendicectomy. This study aimed to explore the preference of the general population regarding operative or antibiotic treatment of uncomplicated appendicitis. METHODS: In this prospective study, a clinical scenario and questionnaire were submitted to a panel comprising a sample of an average adult population. The survey was distributed by an independent, external research bureau, and included a comprehensive explanation of the risks and benefits of both treatment options. The primary outcome was the proportion of participants who would prefer antibiotics over surgery. Secondary outcomes were reasons for this preference and the accepted recurrence rate within 1 year when treated with antibiotics only. All outcomes were weighted for the average Dutch population. RESULTS: Of 254 participants, 49.2 per cent preferred antibiotic treatment for uncomplicated appendicitis, 44.5 per cent preferred surgery, and 6.3 per cent could not make a decision. About half of the participants preferring antibiotics would accept a recurrence risk of more than 50 per cent within 1 year. Avoiding surgery was their main reason. In participants preferring surgery, many tolerated a recurrence risk of no more than 10 per cent when treated with antibiotics. Removal of the cause of appendicitis was their main reason. CONCLUSION: Around half of the average population sample preferred antibiotics over surgical treatment of uncomplicated appendicitis and were willing to accept a high recurrence risk to avoid surgery initially. Participants who preferred surgery tolerated only a very low recurrence risk with antibiotic treatment.

Discriminating complicated from uncomplicated appendicitis by ultrasound imaging, computed tomography or magnetic resonance imaging: systematic review and meta-analysis of diagnostic accuracy.

BACKGROUND: Discriminating complicated from uncomplicated appendicitis is crucial. Patients with suspected complicated appendicitis are best treated by emergency surgery, whereas those with uncomplicated appendicitis may be treated with antibiotics alone. This study aimed to obtain summary estimates of the accuracy of ultrasound imaging, CT and MRI in discriminating complicated from uncomplicated appendicitis. METHODS: A systematic literature review was conducted by an electronic search in PubMed, Embase and the Cochrane Library for studies describing the diagnostic accuracy of complicated versus uncomplicated appendicitis. Studies were included if the population comprised adults, and surgery or pathology was used as a reference standard. Risk of bias and applicability were assessed with QUADAS-2. Bivariable logitnormal random-effect models were used to estimate mean sensitivity and specificity. RESULTS: Two studies reporting on ultrasound imaging, 11 studies on CT, one on MRI, and one on ultrasonography with conditional CT were included. Summary estimates for sensitivity and specificity in detecting complicated appendicitis could be calculated only for CT, because of lack of data for the other imaging modalities. For CT, mean sensitivity was 78 (95 per cent c.i. 64 to 88) per cent, and mean specificity was 91 (85 to 99) per cent. At a median prevalence of 25 per cent, the positive predictive value of CT for complicated appendicitis would be 74 per cent and its negative predictive value 93 per cent. CONCLUSION: Ultrasound imaging, CT and MRI have limitations in discriminating between complicated and uncomplicated appendicitis. Although CT has far from perfect sensitivity, its negative predictive value for complicated appendicitis is high.

Meta-analysis of lower perioperative blood glucose target levels for reduction of surgical-site infection.

BACKGROUND: There is a clear association between hyperglycaemia and surgical-site infection (SSI). Intensive glucose control may involve a risk of hypoglycaemia, which in turn results in potentially severe complications. A systematic review was undertaken of studies comparing intensive versus conventional glucose control protocols in relation to reduction of SSI and other outcomes, including hypoglycaemia, mortality and stroke. METHODS: PubMed, Embase, CENTRAL, CINAHL and WHO databases from 1 January 1990 to 1 August 2015 were searched. Inclusion criteria were RCTs comparing intensive with conventional glucose control protocols, and reporting on the incidence of SSI. Meta-analyses were performed with a random-effects model, and meta-regression was subsequently undertaken. Targeted blood glucose levels, achieved blood glucose levels, and important adverse events were summarized. RESULTS: Fifteen RCTs were included. The summary estimate showed a significant benefit for an intensive compared with a conventional glucose control protocol in reducing SSI (odds ratio (OR) 0·43, 95 per cent c.i. 0·29 to 0·64; P < 0·001). A significantly higher risk of hypoglycaemic events was found for the intensive group compared with the conventional group (OR 5·55, 2·58 to 11·96), with no increased risk of death (OR 0·74, 0·45 to 1·23) or stroke (OR 1·37, 0·26 to 7·20). These results were consistent both in patients with and those without diabetes, and in studies with moderately strict and very strict glucose control. CONCLUSION: Stricter and lower blood glucose target levels of less than 150 mg/dl (8·3 mmol/l), using an intensive protocol in the perioperative period, reduce SSI with an inherent risk of hypoglycaemic events but without a significant increase in serious adverse events.

Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies.

Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.

Comparison of Imaging Strategies with Conditional versus Immediate Contrast-Enhanced Computed Tomography in Patients with Clinical Suspicion of Acute Appendicitis.

OBJECTIVES: To compare the diagnostic accuracy of conditional computed tomography (CT), i.e. CT when initial ultrasound findings are negative or inconclusive, and immediate CT for patients with suspected appendicitis. METHODS: Data were collected within a prospective diagnostic accuracy study on imaging in adults with acute abdominal pain. All patients underwent ultrasound and CT, read by different observers who were blinded from the other modality. Only patients with clinical suspicion of appendicitis were included. An expert panel assigned a final diagnosis to each patient after 6 months of follow-up (clinical reference standard). RESULTS: A total of 422 patients were included with final diagnosis appendicitis in 251 (60 %). For 199 patients (47 %), ultrasound findings were inconclusive or negative. Conditional CT imaging correctly identified 241 of 251 (96 %) appendicitis cases (95 %CI, 92 % to 98 %), versus 238 (95 %) with immediate CT (95 %CI, 91 % to 97 %). The specificity of conditional CT imaging was lower: 77 % (95 %CI, 70 % to 83 %) versus 87 % for immediate CT (95 %CI, 81 % to 91 %). CONCLUSION: A conditional CT strategy correctly identifies as many patients with appendicitis as an immediate CT strategy, and can halve the number of CTs needed. However, conditional CT imaging results in more false positives. KEY POINTS: • Conditional CT (CT after negative/inconclusive ultrasound findings) can be used for suspected appendicitis. • Half the number of CT examinations is needed with a conditional strategy. • Conditional CT correctly identifies as many patients with appendicitis as immediate CT. • Conditional imaging results in more false positive appendicitis cases.

Systematic review and meta-analysis of the open abdomen and temporary abdominal closure techniques in non-trauma patients.

BACKGROUND: Several challenging clinical situations in patients with peritonitis can result in an open abdomen (OA) and subsequent temporary abdominal closure (TAC). Indications and treatment choices differ among surgeons. The risk of fistula development and the possibility to achieve delayed fascial closure differ between techniques. The aim of this study was to review the literature on the OA and TAC in peritonitis patients, to analyze indications and to assess delayed fascial closure, enteroatmospheric fistula and mortality rate, overall and per TAC technique. METHODS: Electronic databases were searched for studies describing the OA in patients of whom 50% or more had peritonitis of a non-traumatic origin. RESULTS: The search identified 74 studies describing 78 patient series, comprising 4,358 patients of which 3,461 (79%) had peritonitis. The overall quality of the included studies was low and the indications for open abdominal management differed considerably. Negative pressure wound therapy (NPWT) was the most frequent described TAC technique (38 of 78 series). The highest weighted fascial closure rate was found in series describing NPWT with continuous mesh or suture mediated fascial traction (6 series, 463 patients: 73.1%, 95% confidence interval 63.3-81.0%) and dynamic retention sutures (5 series, 77 patients: 73.6%, 51.1-88.1%). Weighted rates of fistula varied from 5.7% after NPWT with fascial traction (2.2-14.1%), 14.6% (12.1-17.6%) for NPWT only, and 17.2% after mesh inlay (17.2-29.5%). CONCLUSION: Although the best results in terms of achieving delayed fascial closure and risk of enteroatmospheric fistula were shown for NPWT with continuous fascial traction, the overall quality of the available evidence was poor, and uniform recommendations cannot be made.

Comparison of micro-CT and cone beam CT-based assessments for relative difference of grey level distribution in a human mandible.

OBJECTIVES: The purpose of this study was to examine the ability of CT to assess the relative difference of degree of bone mineralization (grey level) parameters in a human mandible. METHODS: Ten mandibular sections from cadavers (81.5 ± 12.1 years) were scanned using micro-CT with 27.2 µm voxel size and cone beam CT (CBCT) with 200 µm, 300 µm, and 400 µm voxel sizes. In addition, 15 clinical CBCT images from young patients (mean age 18.9 ± 3.3 years) were identified. After segmentation of bone voxels, alveolar bone and basal cortical bone regions were digitally isolated. A histogram of grey level, which is equivalent to degree of bone mineralization, was obtained from each region of the CT images. Mean, standard deviation (SD), coefficient of variation (COV), fifth percentile low (Low(5)) and high (High(5)) of alveolar bone and basal cortical bone regions were obtained. Percentage differences of grey level parameters between alveolar and basal cortical bones were computed. RESULTS: The alveolar bone region had significantly lower Mean, Low(5) and High(5) values but significantly higher SD and COV than the basal cortical bone region for all CT images (p < 0.05). All parameters were significantly lower for the old cadaver group than for the young patient group (p < 0.05). CONCLUSIONS: CBCT and micro-CT provide comparable results in the assessment of relative difference in grey level distribution between alveolar and basal cortical bone regions in the human mandible. The percentage difference relative to an internal reference (basal cortical bone) can be a reliable method when assessing the degree of bone mineralization using CBCT images for both cross-sectional and longitudinal comparisons.

Systematic review and meta-analysis of somatostatin analogues for the treatment of pancreatic fistula.

BACKGROUND: Somatostatin analogues are used for the treatment of pancreatic fistula, with the aim of achieving fistula closure or reduction of output. METHOD: MEDLINE, Embase and Cochrane databases were searched systematically for relevant articles followed by hand-searching of reference lists. Data on patient recruitment, intervention and outcome were extracted and meta-analysis performed where reasonable. RESULTS: Seven randomized clinical trials met the inclusion criteria and included a total of 297 patients with fistulas of the gastrointestinal tract; of these, 102 patients had fistulas of pancreatic origin. Pooling of closure rates showed no significant difference between patients treated with somatostatin analogues compared with controls: odds ratio 1·52 (95 per cent confidence interval 0·88 to 2·61). Owing to inconsistent descriptions, pooling of results was not possible for other endpoints, such as time to fistula closure. CONCLUSION: There is no solid evidence that somatostatin analogues result in a higher closure rate of pancreatic fistula compared with other treatments.

Variation in reproductive traits is associated with short anogenital distance in female rats.

Anogenital distance was used as a biomarker for natural variation in prenatal androgenization of female rats and was associated with individual differences in a suite of reproductive characteristics. Females with short anogenital distances were likely to have first vaginal estrus earlier than females with longer anogenital distances and to have first vaginal estrus on the same day as vaginal opening. In young adulthood, females with short anogenital distances had shorter ovarian cycles and less intense lordosis reflexes in response to manual palpation than those with longer anogenital distances, but only when living individually, not in groups. Taken together, these findings indicate that prenatal androgenization affects reproductive traits throughout the life span.

Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 microg day(-1)) versus HFA-fluticasone propionate (1000 microg day(-1)) in patients with asthma.

Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extra-fine aerosol and HFA-fluticasone propionate (HFA-FP) are chlorofluorocarbon-free inhalers. We conducted an 8-week, open study to demonstrate the equivalence of HFA-BDP (800 microg day(-1)) and HFA-FP (1000 microg day(-1)) in moderate to severe asthma. Symptomatic patients on 500-1000 microg day(-1) CFC-BDP (or equivalent) and short-acting beta-agonist, were randomized to HFA-BDP (n = 101) or HFA-FP (n = 97) after 7-14 (+/-2) day run-in. In the intent-to-treat (ITT) population (n = 198), both treatments provided clinically and statistically significant improvements in asthma control, with increases in peak expiratory flow in the morning (AM PEF) and asthma symptoms (within treatment analysis P<0.05). Mean (SE) change in AM PEF from baseline at week 8 was equivalent (defined as 90% CI for the mean difference between treatments within +/-25 l min(-1)) in the two groups: 29.59 (5.19) l min(-1) for HFA-BDP vs. 17.3 (5.45) l min(-1) for HFA-FP (90% CI-0.02, 24.91). For the perprotocol population (n = 121), the mean (SE) change in AM PEF from baseline was not equivalent; AM PEF improved to a significantly greater extent in the HFA-BDP group than HFA-FP group [34.84 (7.08) vs. 20.63 (7.32) l min(-1) P<0.01; 90% CI; 2.66, 31.10]. At week 8 in the ITT population, there were no statistically significant differences in FEV1, beta-agonist use, asthma symptom/sleep disturbance scores, or percentage of days without asthma symptoms/sleep disturbance. There was a significantly greater reduction from baseline in mean eosinophil count for HFA-BDP compared with HFA-FP at weeks 3 and 8 (P<0.01), and eosinophil cationic protein value at week 8 (P<0.01). Both treatments were well tolerated and there were no statistically significant differences in urinary cortisol creatinine parameters. In conclusion, this study showed that, in patients with moderate-to-severe symptomatic asthma, HFA-BDP extra-fine aerosol 800 microg(-1) was at least as effective and equally well tolerated as 1000 microg day(-1) HFA-FP.

Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study.

BACKGROUND: CDE (cyclophosphamide, doxorubicin, etoposide) is one of the standard chemotherapy regimens in the treatment of small-cell lung cancer (SCLC), with myelosuppression as dose-limiting toxicity. In this trial the impact of prophylactic antibiotics on incidence of febrile leucopenia (FL) during chemotherapy for SCLC was evaluated. PATIENTS AND METHODS: Patients with chemo-naïve SCLC were randomized to standard-dose CDE (C 1,000 mg/m2 day 1, D 45 mg/m2 day 1, E 100 mg/m2 days 1-3. i.v., q 3 weeks, x5) or to intensified CDE chemotherapy (125% dose, q 2 weeks, x4, with filgrastim 5 microg/kg/day days 4-13) to assess the impact on survival (n = 240 patients). Patients were also randomized to prophylactic antibiotics (ciprofloxacin 750 mg plus roxithromycin 150 mg, bid. days 4-13) or to placebo in a 2 x 2 factorial design (first 163 patients). This manuscript focuses on the antibiotics question. RESULTS: The incidence of FL during the first cycle was 25% of patients in the placebo and 11% in the antibiotics arm (P = 0.010; 1-sided), with an overall incidence through all cycles of 43% vs. 24% respectively (P = 0.007; 1-sided). There were less Gram-positive (12 vs. 4), Gram-negative (20 vs. 5) and clinically documented (38 vs. 15) infections in the antibiotics arm. The use of therapeutic antibiotics was reduced (P = 0.013; 1-sided), with less hospitalizations due to FL (31 vs. 17 patients, P = 0.013: 1-sided). However, the overall number of days of hospitalization was not reduced (P = 0.05; 1-sided). The number of infectious deaths was nil in the antibiotics vs. five (6%) in the placebo arm (P = 0.022; 2-sided). CONCLUSIONS: Prophylactic ciprofloxacin plus roxithromycin during CDE chemotherapy reduced the incidence of FL, the number of infections, the use of therapeutic antibiotics and hospitalizations due to FL by approximately 50%, with reduced number of infectious deaths. For patients with similar risk for FL, the prophylactic use of antibiotics should be considered.

Treating problem-solving deficits on an acute care psychiatric inpatient unit.

Neuropsychological deficits in problem-solving are commonly found in patients with schizophrenia and severe affective disorders. However, in an acute care setting, treatment efforts do not typically target these deficits, even though they can impede recovery. This study aimed to evaluate the effectiveness of short-term problem-solving remediation in acutely ill psychiatric inpatients. Twenty-eight psychiatric inpatients identified as having a verbal problem-solving deficit received 6 h of either verbal problem-solving remediation or placebo instruction. Before and after treatment a nurse rated the patient's psychiatric status and the patient completed verbal and nonverbal problem-solving tests, and a self-report rating of symptoms and ability to cope with symptoms. Both groups of patients improved on the measure of verbal problem solving, but those receiving problem-solving remediation improved significantly more. Both groups made symptomatic improvement, but the patients receiving problem-solving remediation made significantly more improvement on the measure of coping ability and the nurses rated them as more improved, both psychiatrically and with regard to coping skills. Verbal problem-solving deficits are responsive to short-term remediation in an acute care setting, and treatment effects may generalize to improve ability to cope with psychiatric symptoms.

Gemcitabine and cisplatin as induction regimen for patients with biopsy-proven stage IIIA N2 non-small-cell lung cancer: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC 08955).

PURPOSE: Our objective was to better define the activity/feasibility of gemcitabine/cisplatin (GC) as induction chemotherapy in patients with stage IIIA N2 non-small-cell lung cancer (NSCLC) followed by surgery or radiotherapy within a large, ongoing comparative study (EORTC 08941). PATIENTS AND METHODS: Forty-seven chemotherapy-naive patients with NSCLC, median age of 58 years, stage IIIA N2 disease, World Health Organization performance status of 0 or 1, and the ability to tolerate a pneumonectomy received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and cisplatin 100 mg/m(2) on day 2, every 4 weeks. Patients received induction chemotherapy (three cycles) before re-evaluation and randomization to surgery or radiotherapy. RESULTS: Grade 3/4 thrombocytopenia, the main hematologic toxicity, occurred in 60% of patients but was not associated with bleeding. Full-dose gemcitabine was given in 48% of the courses. Severe nonhematologic toxicity was uncommon. Two patients with preexisting, autoimmune pulmonary fibrosis had deterioration of pulmonary function after radiotherapy. Thirty-three (70.2%; 95% confidence interval, 55.1% to 82.7%) of the 47 eligible patients had objective responses (three complete responses and 30 partial responses). Mediastinal nodes were tumor-free after induction therapy in 53% of cases. Resections were considered complete in 71% of the patients who underwent thoracotomy after induction therapy. Median survival for all recruited patients (N = 53) was 18.9 months, with an estimated 1-year survival rate of 69%. CONCLUSION: In patients with N2 stage IIIA NSCLC, GC is a highly active and well-tolerated induction regimen. GC should be explored in combination with surgery or radiotherapy in stage I and II patients.

Long term survival of a patient with malignant pleural mesothelioma as a late complication of radiotherapy for Hodgkin's disease treated with 90yttrium-silicate.

A case of malignant pleural mesothelioma (PM) 24 years after thoracic radiotherapy for Hodgkin's disease is presented. As primary treatment and to relieve symptoms of dyspnea secondary to pleural effusion a thoracic drain was installed, followed by intracavitary radiation therapy with 90yttrium-silicate. Minor complaints of fever and a dry cough as a side-effect of this treatment were effectively treated with prednisone during 2 weeks. The patient remains in a good clinical condition now 6 years after diagnosis. Considering the few therapeutic options the use of 90yttrium-silicate intrapleural installation could be propagated as a safe and effective antitumour treatment for a selected group of patients with malignant PM.

Infusions of lidocaine into the amygdala, but not the preoptic area, block pseudopregnancy in the rat.

In the rat, vaginocervical stimulation (VCS) received during mating is required for the subsequent expression of 10-12 days of twice-daily prolactin surges that are necessary for pregnancy or pseudopregnancy (PSP). This temporal separation of sensory stimulus and neuroendocrine response suggests that a mnemonic of the vaginocervical stimulation is created in the brain that triggers and sustains the daily prolactin surges. We investigated the possible involvement of the medial preoptic area (mPOA) and the medial amygdala (mAMYG) as potential neural sites involved in the processing of this neuroendocrine arc. Cycling female rats were bilaterally implanted with intracerebral cannulae in either the mPOA or mAMYG. On proestrus, females were manually palpated to confirm sexual receptivity and then received bilateral infusions of either the local anesthetic lidocaine, the Ca(++) channel blocker, verapamil, or phosphate-buffered saline (PBS) into either brain site before or both before and after receipt of 15 intromissions from an experienced male. Unmated control females received comparable infusions of lidocaine or verapamil, and were placed in the empty test arena for 10 min. Infusions consisted of either a single bilateral infusion 15 min before mating (Expt. 1), bilateral infusions both 15 min before and after mating (Expt. 2) or eight bilateral infusions separated by 30 min intervals spanning a period beginning 45 min before and ending 2 h 45 min after mating (Expt. 3). None of the lidocaine infusions into the mPOA prevented the establishment of PSP, and neither verapamil infusions into the mAMYG nor the shorter-term neural block (i.e. single or double lidocaine infusions) of the mAMYG prevented mating-induced PSP. However, the longer-term neural block (i.e. multiple lidocaine infusions) of the mAMYG significantly reduced the incidence of PSP. These data support previous findings that the mAMYG receives sensory input from VCS, and suggest that the mAMYG is a site at which a mnemonic of VCS is established.

Endocrine basis for two types of individual differences in lordosis reflex intensity.

We have identified individual differences in two independent types of lordosis reflex intensity. Overall lordosis reflex intensity, averaged across 9.4 +/- 0.99 days (range = 1-18 days), differs among cycling individuals and is a biomarker for the rate and pattern of reproductive aging. Although estrogen is necessary to permit lordosis reflex responding and manifests individual differences throughout the estrous cycle, it was individual differences in progesterone that correlated negatively with the individual variation in overall lordosis reflex intensity; females with intense overall lordosis reflexes had low progesterone throughout the estrous cycle. Independent of their overall reflex intensity, females also displayed individual variation in lordosis reflex intensity on proestrus. Among females that still maintained a cyclic lordosis reflex, those with intense lordosis reflexes on proestrus had high levels of luteinizing hormone (LH) at lights out. Among females that displayed intense lordosis reflexes throughout the estrous cycle (i.e., had entered constant lordosis), those with intense proestrous lordosis reflexes had low levels of LH at lights out on proestrus. Females who had entered constant lordosis tended to have lower overall progesterone than females who still maintained cyclic patterns of lordosis. Thus, constant lordosis was identified as an important component of the changes of reproductive aging.

[Bronchiectases; clinical aspects, diagnosis and treatment]. / Bronchiëctasieën; kliniek, diagnostiek en behandeling.

Localised bronchiectasis was diagnosed in three immigrants, a male aged 16 and two females aged 45 and 20 years old. The symptoms were productive coughing (purulent discharge) and (or) haemoptysis. All recovered after surgical resection of the diseased lung parts. With the growing population of immigrants in the Netherlands it is of great importance to consider the presence of localised bronchiectasis in patients from this population who present with a persistent or recurrent bronchopneumonia.

Individual differences among female rats in the timing of the preovulatory LH surge are predicted by lordosis reflex intensity.

In young female rats, we found individual differences in LH surge characteristics that could underlie differences in fertility throughout adulthood and aging. We modified a jugular cannulation technique, which enabled us to characterize four successive proestrous LH surges in regularly cycling female rats. During a surge, the timing and amount of LH were negatively correlated, so that late-onset surges reached a low peak, late in the day. Within a female rat, the timing of the LH surge, but not the blood level of LH, was stable from cycle to cycle. Thus, differences in onset and peak time between successive LH surges within one female were less than differences among females. Moreover, these individual differences in timing of the LH surge were positively correlated with individual differences in lordosis reflex intensity on proestrus. Females with early-onset LH surges had high average lordosis reflex intensity on proestrus. Therefore, lordosis reflex intensity is a nonintrusive behavioral biomarker for individual differences in the timing of the preovulatory LH surge. This relationship between behavior and the preovulatory LH surge may reflect a hormonal basis for variations in reproductive strategies throughout the life span.