Effect of weight change on progression of knee OA structural features assessed by MRI in overweight and obese women.

OBJECTIVE: To evaluate the effects of weight change on progression of knee osteoarthritis (OA) structural features by magnetic resonance imaging (MRI) in overweight and obese women without clinical knee OA. DESIGN: 347 participants from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study were classified with latent class growth analysis into a subgroup with steady weight (n = 260; +0.1 ± 4.0 kg, +0.2 ± 4.4%), weight gain (n = 43; +8.6 ± 4.0 kg, +9.8 ± 4.1%) or weight loss (n = 44; -9.0 ± 7.2 kg, -9.8 ± 7.5%) over 2.5 years. Baseline and follow-up 1.5T MRIs were scored with MRI Osteoarthritis Knee Score (MOAKS) for progression of bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities, meniscal extrusion and synovitis. Associations between subgroups and change in MRI features at knee-level were assessed using adjusted Generalized Estimating Equations. RESULTS: 687 knees from 347 women (median age 55.2 years, interquartile range (IQR) 5.5, median body mass index (BMI) 31.2 kg/m2, IQR 5.3) were analyzed. Progression of synovitis was 18% in the weight gain vs 7% in the stable weight subgroup (OR 2.88; 95%CI 1.39-5.94). The odds for progression of patellofemoral (PF) BMLs and cartilage defects increased with 62% (OR 1.62; 95%CI 0.92-2.84) and 53% (OR 1.53; 95%CI 0.92-2.56) in the weight gain vs the stable weight subgroup. CONCLUSIONS: In overweight and obese women, progression of synovitis increased more than 2.5 times in a weight gain compared to a stable weight subgroup over 2.5 years. Large effect sizes were also found for the difference in progression of PF BMLs and PF cartilage defects between the weight gain and stable weight subgroup.

A novel succinate dehydrogenase subunit B germline variant associated with head and neck paraganglioma in a Dutch kindred: A family-based study.

OBJECTIVE: In the Netherlands, the majority of hereditary head and neck paragangliomas (HNPGL) are caused by germline variants in the succinate dehydrogenase genes (SDHD, SDHB, SDHAF2). Here, we evaluate a four-generation family linked to a novel SDHB gene variant with the manifestation of a HNPGL. DESIGN: A family-based study. SETTING: The VU University Medical Center (VUmc) Amsterdam, a tertiary clinic for Otolaryngology and Head and Neck Surgery. PARTICIPANTS AND MAIN OUTCOME MEASURES: The index patients presented with an embryonic rhabdomyosarcoma and a non-Hodgkin lymphoma. Array-based comparative genomic hybridisation (aCGH) analysis and multiplex ligation-dependent probe amplification (MLPA) revealed a novel deletion of exon 1-3 in the SDHB gene, suspected to predispose to paraganglioma (PGL)/pheochromocytoma (PHEO) syndrome type 4. Subsequently, genetic counselling and DNA testing were offered to all family members at risk. Individuals that tested positive for this novel SDHB gene variant were counselled and additional clinical evaluation was offered for the identification of HNPGL and/or PHEO. RESULTS: The DNA of 18 family members was tested, resulting in the identification of 10 carriers of the exon 1-3 deletion in the SDHB gene. One carrier was diagnosed with a carotid body PGL and serum catecholamine excess, which was surgically excised. Negative SDHB immunostaining of the carotid body tumour confirmed that it was caused by the SDHB variant. The remaining 9 carriers showed no evidence of PGL/PHEO. CONCLUSION: Deletion of exon 1-3 in the SDHB gene is a novel germline variant associated with the formation of hereditary HNPGL.

Sources of errors and uncertainties in the assessment of forest soil carbon stocks at different scales-review and recommendations.

Spatially explicit knowledge of recent and past soil organic carbon (SOC) stocks in forests will improve our understanding of the effect of human- and non-human-induced changes on forest C fluxes. For SOC accounting, a minimum detectable difference must be defined in order to adequately determine temporal changes and spatial differences in SOC. This requires sufficiently detailed data to predict SOC stocks at appropriate scales within the required accuracy so that only significant changes are accounted for. When designing sampling campaigns, taking into account factors influencing SOC spatial and temporal distribution (such as soil type, topography, climate and vegetation) are needed to optimise sampling depths and numbers of samples, thereby ensuring that samples accurately reflect the distribution of SOC at a site. Furthermore, the appropriate scales related to the research question need to be defined: profile, plot, forests, catchment, national or wider. Scaling up SOC stocks from point sample to landscape unit is challenging, and thus requires reliable baseline data. Knowledge of the associated uncertainties related to SOC measures at each particular scale and how to reduce them is crucial for assessing SOC stocks with the highest possible accuracy at each scale. This review identifies where potential sources of errors and uncertainties related to forest SOC stock estimation occur at five different scales-sample, profile, plot, landscape/regional and European. Recommendations are also provided on how to reduce forest SOC uncertainties and increase efficiency of SOC assessment at each scale.

Predictors of clinical effectiveness of Hymenoptera venom immunotherapy.

BACKGROUND: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors, of which the relative importance is unknown. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC), mastocytosis in the skin (MIS) and of other parameters with the frequency of objective systemic reactions during in-hospital sting challenge (SC). METHODS: In this observational retrospective study, we enrolled 1532 patients (1609 cases due to double SC) with established honeybee or vespid venom allergy who had undergone VIT and a subsequent SC. Data were collected on various putative risk factors. Adult-onset MIS and/or a BTC > 20.0 µg/L was defined as clinical indicators of systemic mastocytosis. Relative rates were calculated with logistic regression models. RESULTS: Ninety-eight patients (6.4%) presented with MIS and/or BTC > 20.0 µg/L. 104 cases (6.5%) developed objective generalized symptoms during SC. In the absence of MIS, a BTC ≤ 20 µg/L did not increase the risk for VIT failure. The most important factors associated with a worse outcome were ACE inhibitor medication (OR 5.24, 95% CI 1.83-13.00, P < 0.001), honeybee venom allergy (OR 5.09, 95% CI 3.17-8.15, P < 0.001), systemic allergic reaction during VIT (OR 3.07, 95% CI 1.79-5.14, P < 0.001), and a substantial likelihood to suffer from SM (OR 2.74, 95% CI 1.37-5.22, P = 0.003), whereas a double VIT (OR 0.51, 95% CI 0.27-0.90, P = 0.027) and a longer duration of therapy (OR 0.68 per treatment month, 95% CI 0.50-0.93, P = 0.017) reduced the failure rate. CONCLUSION: The magnitude of therapeutic success correlates with type of venom, duration of therapy, and venom dose. Adult-onset MIS and/or a BTC > 20 µg/L is a significant, albeit not the strongest determinant for VIT failure. According to its odds ratio, ACE inhibitor therapy appears to be associated with the highest risk for VIT failure.

Rapid profiling of enteric coated drug delivery spheres via broadband acoustic resonance dissolution spectroscopy (BARDS).

There is an increased trend towards the use of drug and enteric coated sugar spheres for controlled oral delivery of active pharmaceutical ingredients (API). This trend is driven by increased efficacy and ease of formulation of different dosage levels. However, difficulties exist in determining the thickness of drug and enteric coatings in a time efficient manner during manufacture, quality assurance and stability testing. The thickness of the coating determines the dosage of the API and the thickness of the enteric coating determines the release rate of the drug in the gastro-intestinal tract. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) offers a rapid new approach to characterising the enteric coating thickness and the raw materials used in their manufacture. BARDS applications are based on reproducible changes in the compressibility of a solvent during dissolution which is monitored acoustically due to associated changes in the speed of sound in solution. It is demonstrated how core delivery sugar spheres have unique acoustic spectra attributable to the mean size distribution of the spheres. A steady state acoustic lag time is associated with the disintegration of the enteric coating, in basic solution. This lag time can be manipulated by varying the concentration of the base which affects the rate at which the coating dissolves. It is anticipated that the thickness/loading of the spheres can be estimated from the lag time.

The organisation of universal newborn hearing screening in the Wallonia-Brussels Federation.

OBJECTIVE: A universal newborn hearing screening programme based on the voluntary participation of maternity hospitals has been implemented in the Wallonia-Brussels Federation since November 2006. This paper presents the results of this programme and its evolution since its implementation (2007-2011). METHOD: Two-step screening by automated otoacoustic emissions is performed on newborns without risk factors for hearing loss and, if abnormal responses or risk factor(s) are found, auditory brainstem response audiometry is performed. Descriptive analyses of the eligible population, coverage rates and prevalence of hearing loss were presented by year of birth (2007-2011) and globally. RESULTS: Over five years, the first screening test coverage rate increased to almost 95%, 2.4% of the newborns without risk factors were referred for auditory brainstem response audiometry and 42.6% of the newborns referred were lost to followup. Of the newborns with risk factor(s) for hearing loss, 6.3% were not tested, 87.4% had normal bilateral hearing and 3.7% were lost to follow-up. Between 2007 and 2011, hearing impairment was reported in 3.18 per thousand newborns eligible for the programme, whatever the kind of hearing loss. CONCLUSIONS: Like many other countries and areas, the Wallonia-Brussels Federation has implemented a universal newborn hearing screening programme. The results of this programme evolved favourably during the period 2007-2011, even if some efforts had to be made to improve the follow-up of the referred newborns and data quality.

Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study.

BACKGROUND: Induction chemotherapy has been suggested to impact on preoperative chemoradiation efficacy in locally advanced rectal cancer (LARC). To evaluate in LARC patients, the feasibility and efficacy of a short intense course of induction oxaliplatin before preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: Patients with T2-T4/N+ rectal adenocarcinoma were randomly assigned to arm A-preoperative CRT with 5-fluorouracil (5-FU) continuous infusion followed by surgery-or arm B-induction oxaliplatin, folinic acid and 5-FU followed by CRT and surgery. The primary end point was the rate of ypT0-1N0 stage achievement. RESULTS: Fifty seven patients were randomly assigned (arm A/B: 29/28) and evaluated for planned interim analysis. On an intention-to-treat basis, the ypT0-1N0 rate for arms A and B were 34.5% (95% CI: 17.2% to 51.8%) and 32.1% (95% CI: 14.8% to 49.4%), respectively, and the study therefore was closed prematurely for futility. There were no statistically significant differences in other end points including pathological complete response, tumor regression and sphincter preservation. Completion of the preoperative CRT sequence was similar in both groups. Grade 3/4 toxicity was significantly higher in arm B. CONCLUSIONS: Short intense induction oxaliplatin is feasible in LARC patients without compromising the preoperative CRT completion, although the current analysis does not indicate increased locoregional impact on standard therapy.

Deep learning body-composition analysis of clinically acquired CT-scans estimates creatinine excretion with high accuracy in patients and healthy individuals.

Assessment of daily creatinine production and excretion plays a crucial role in the estimation of renal function. Creatinine excretion is estimated by creatinine excretion equations and implicitly in eGFR equations like MDRD and CKD-EPI. These equations are however unreliable in patients with aberrant body composition. In this study we developed and validated equations estimating creatinine production using deep learning body-composition analysis of clinically acquired CT-scans. We retrospectively included patients in our center that received any CT-scan including the abdomen and had a 24-h urine collection within 2 weeks of the scan (n = 636). To validate the equations in healthy individuals, we included a kidney donor dataset (n = 287). We used a deep learning algorithm to segment muscle and fat at the 3rd lumbar vertebra, calculate surface areas and extract radiomics parameters. Two equations for CT-based estimate of RenAl FuncTion (CRAFT 1 including CT parameters, age, weight, and stature and CRAFT 2 excluding weight and stature) were developed and compared to the Cockcroft-Gault and the Ix equations. CRAFT1 and CRAFT 2 were both unbiased (MPE = 0.18 and 0.16 mmol/day, respectively) and accurate (RMSE = 2.68 and 2.78 mmol/day, respectively) in the patient dataset and were more accurate than the Ix (RMSE = 3.46 mmol/day) and Cockcroft-Gault equation (RMSE = 3.52 mmol/day). In healthy kidney donors, CRAFT 1 and CRAFT 2 remained unbiased (MPE = - 0.71 and - 0.73 mmol/day respectively) and accurate (RMSE = 1.86 and 1.97 mmol/day, respectively). Deep learning-based extraction of body-composition parameters from abdominal CT-scans can be used to reliably estimate creatinine production in both patients as well as healthy individuals. The presented algorithm can improve the estimation of renal function in patients who have recently had a CT scan. The proposed methods provide an improved estimation of renal function that is fully automatic and can be readily implemented in routine clinical practice.

Contrast-enhanced magnetic resonance angiography (MRA): evaluation of three different contrast agents at two different doses (0.05 and 0.1 mmol/kg) in pigs at 1.5 Tesla.

OBJECTIVE: To compare the image quality of contrast-enhanced magnetic resonance angiography (CE-MRA) of the supra-aortic vessels at 0.05 mmol/kg bw and 0.1 mmol/kg bw, between gadobutrol, Gd-DTPA and Gd-BOPTA quantitatively and qualitatively a total of eight pigs were evaluated intraindividually at 1.5 T. METHODS: Each pig was examined using 0.1 mmol/kg gadobutrol, Gd-DTPA and Gd-BOPTA on day one and 0.05 mmol/kg on day two. MRA datasets for the carotid artery and the infraorbital artery were qualitatively assessed regarding overall image quality on an ordinal four-point scale (4-excellent, 1-non-diagnostic). The signal-to noise-ratio (SNR) was measured. RESULTS: The qualitative assessment of the carotid artery showed a higher median image quality for the 0.1 mmol dose than for the 0.05 mmol dose for all three compounds. No difference was found for the infraorbital artery. Mean SNR of Gd-BOPTA, Gd-DTPA, gadobutrol at 0.05 mmol/kg were 36.0 ± 13.4/37.9 ± 16.3/43.7 ± 0.4 and at 0.1 mmol/kg they were 50.1 ± 12.4/46.6 ± 6.5 / 54.6 ± 10.2. Gd-BOPTA 0.05 revealed a significantly lower SNR than all other agents at normal dose. CONCLUSIONS: Full-dose gadolinium MRA results in higher image quality and significantly higher SNR compared with the half dose. Gadobutrol and Gd-BOPTA have similar enhancement properties at full dose but at half dose, gadobutrol appears superior.

Comparison of 2 different regimens for reactogenicity, safety, and immunogenicity of the live attenuated oral rotavirus vaccine RIX4414 coadministered with oral polio vaccine in South African infants.

BACKGROUND: A phase II, randomized, double-blind, placebo-controlled study was conducted in South Africa during 2003-2004 to evaluate the safety, reactogenicity, and immunogenicity of 2 regimens of the live attenuated oral human rotavirus vaccine RIX4414 when coadministered with the Expanded Program on Immunization childhood vaccines, including oral polio vaccine. METHODS: Healthy infants were randomized (2:2:1) to receive either 2 doses of RIX4414 (n = 190; at 10 and 14 weeks, with placebo at 6 weeks), 3 doses of RIX4414 (n = 189; at 6, 10, and 14 weeks), or 3 doses of placebo (n = 96), all with concomitant routine vaccinations. The antirotavirus IgA seroconversion rate was assessed using enzyme-linked immunosorbent assay at 2 months after the last dose of RIX4414 or placebo. Antipolio types 1, 2, and 3 antibodies were measured using a virus neutralization assay. Solicited symptoms were recorded for 15 days after each dose. RESULTS: The antirotavirus IgA seroconversion rates were similar in the RIX4414 2- and 3-dose groups (44.3% and 44.4%, respectively; P = .544, by 1-sided Fisher exact test) and antirotavirus IgA geometric mean concentrations were also comparable. Seroprotection rates for antipolio types 1, 2, and 3 antibodies were high (93%-100%) and were not significantly different among groups. Solicited symptoms reported within 15 days after vaccination were similar in all groups. CONCLUSIONS: The immune seroconversion response to the RIX4414 vaccine with 3 doses was not superior to the 2-dose regimen. There was no interference by either regimen with antibody response to oral polio vaccine, and RIX4414 was well tolerated when given with routine vaccinations.

Deep Learning-Based Data-Point Precise R-Peak Detection in Single-Lead Electrocardiograms.

Low-cost wearables with capability to record electrocardiograms (ECG) are becoming increasingly available. These wearables typically acquire single-lead ECGs that are mainly used for screening of cardiac arrhythmias such as atrial fibrillation. Most arrhythmias are characteruzed by changes in the RR-interval, hence automatic methods to diagnose arrythmia may utilize R-peak detection. Existing R-peak detection methods are fairly accurate but have limited precision. To enable data-point precise detection of R-peaks, we propose a method that uses a fully convolutional dilated neural network. The network is trained and evaluated with manually annotated R-peaks in a heterogeneous set of ECGs that contain a wide range of cardiac rhythms and acquisition noise. 700 randomly chosen ECGs from the PhysioNet/CinC challenge 2017 were used for training (n=500), validation (n=100) and testing (n=100). The network achieves a precision of 0.910, recall of 0.926, and an F1-score of 0.918 on the test set. Our data-point precise R-peak detector may be important step towards fully automatic cardiac arrhythmia detection.Clinical relevance- This method enables data-point precise detection of R-peaks that provides a basis for detection and characterization of arrhythmias.

Do surgical distal bypasses still play a role in the treatment of critical limb ischemia?

AIM: The treatment of critical limb ischemia is at present very controversial. In fact surgery using different grafts (venous or prosthetic) is in competition with percutaneous angioplasty. Progresses of endoluminal techniques brought certain authors to think that angioplasty is now the first treatment of critical limb ischemia. The aim of the study hereby is to compare our results of distal venous bypasses to the results obtained in literature with venous or other grafts and to those of the percutaneous angioplasty. MATERIAL AND METHOD: In this retrospective study of 113 operated cases between January 2003 and December 2006 by four surgeons, 21 cases are excluded considering the lack of data. Among the remaining 92 cases, the average age is 68.1 years. Men represent 79.4%. Comorbidities include: COPD 55.4%, coronary artery disease 60.9%, diabetes 44.6%, dyslipidemia 66.3% and dialysis 9.8%. Surgical revision was necessary in 29.4%. There were 30.4% stage III limb ischemia and 62% stage IV. Acute ischemia was present in 7.6% of patients. The proximal anastomosis of the bypass is femoral except for 13 cases. The outflow artery is always sural or even more distal. RESULTS: Perioperative mortality is of 2.2% (two cases). The average follow up was of 26.2 months (0.16-64). Eleven patients required subsequent amputation. The primary patency at 1, 3 and 5 years was respectively of 82.1%, 70.6% and 55.9% while limb salvage was respectively of 87.4%, 85.9% and 85.9% at the same intervals. CONCLUSION: Comparing our results to those of the literature for venous or prosthetic bypasses and distal angioplasties, we remain convinced of the high efficiency, on the long run, of infra-popliteal venous bypass grafts. Meanwhile, recent data on distal angioplasties are promising and in constant progress.

[Giant renal cyst as cause of colic obstruction]. / Un kyste rénal géant comme cause d'obstruction colique.

A 97-year old woman presented with a 2-months history of asthenia, loss of appetite, nauseas and intermittent diarrhea. She presented an important colic distension associated to an inflammatory syndrome. Microbiological documentation (blood, urine, saddles stool) was negative. Abdominal computed tomography (CT) showed a 15 cm of diameter (giant) right cortical renal cyst with colic obstruction by external colic compression. A percutaneous cyst drainage was performed allowing the evacuation of 1,500 cc. The fluid culture was positive for Raoultella ornithinolytica and Enterococcus faecalis. No antibiotics were given but inflammatory syndrome remained within normal value. Colic function remained normal.

[Competent and diverse. Portrayal of older adults in Dutch television commercials ten years later]. / Competent en veelzijdig. Representatie van ouderen in de ster-reclame tien jaar later.

The present study replicates our study of older adults' portrayal in Dutch television commercials conducted in 1993. The central question is whether older adults are being portrayed more visibly in Dutch television commercials and whether this portrayal has become more diverse compared to ten years ago. Based on a list of descriptions of all commercials broadcasted by public television channels in 2003 (N= 4767) 117 commercials featuring older adults were selected. By means of a quantitative content analysis it was examined whether and how older men and women are portrayed. It was concluded that although older adults are not more prevalent compared to ten years ago, their portrayal is more diverse with respect to their roles and the advertised products. Older adults were portrayed as more competent and less age-stereotypical in television commercials.

A rotavirus vaccine for infants: the Asian experience.

INTRODUCTION: Severe rotavirus gastroenteritis in children causes significant morbidity worldwide and substantial deaths in developing countries. Hence, a live attenuated vaccine Rotarix was developed with human strain RIX4414 of G1P1A P[8] specificity. RIX4414 trials in infants have begun in developed and developing countries worldwide. An overview of RIX4414 in developed and developing countries and prospects with this vaccine in Asia are presented. METHODS: Completed RIX4414 trials have been reviewed. RESULTS: Two oral doses of RIX4414 were well tolerated with a reactogenicity profile similar to placebo. RIX4414 was also highly immunogenic, e.g., in a dose-ranging study conducted in Singapore, 98.8% to 100% of infants had a vaccine take after 2 doses. RIX4414 did not affect the immune response of simultaneously administered routine infant vaccines. RIX4414 significantly reduced severe rotavirus gastroenteritis in settings where multiple serotypes including the emerging G9 type co-circulated. CONCLUSION: These encouraging results warrant further evaluation of the vaccine worldwide and especially in developing countries with the highest need. Therefore, evaluation of the Rotarix vaccine is continuing in large phase III trials in Asia and worldwide.

Parallel fibers synchronize spontaneous activity in cerebellar Golgi cells.

Cerebellar Golgi cells inhibit their afferent interneurons, the excitatory granule cells. Such a feedback inhibition causes both inhibitory and excitatory neurons in the circuit to synchronize. Our modeling work predicts that the long granule cell axons, the parallel fibers, entrain many Golgi cells and their afferent granule cells in a single synchronous rhythm. Spontaneous activity of 42 pairs of putative Golgi cells was recorded in anesthetized rats to test these predictions. In 25 of 26 pairs of Golgi cells that were positioned along the transverse axis, and presumed to receive common parallel fiber input, spontaneous activity showed a high level of coherence (mean Z score > 6). Conversely, 12 of 16 Golgi cell pairs positioned along the parasagittal axis (no common parallel fiber input) were not synchronized; 4 of 16 of them showed only low levels of synchronicity (mean Z score < 4). For transverse pairs the accuracy of the coherence, measured as the width at half-height of the central peak of the cross-correlogram, was rather low (29.8 +/- 12.5 msec) but increased with Golgi cell firing rate, as predicted by the model. These results suggest that in addition to their role as gain controllers, cerebellar Golgi cells may control the timing of granule cell spiking.

Somatotopic and laminar organization of fos-like immunoreactivity in the medullary and upper cervical dorsal horn induced by noxious facial stimulation in the rat.

The distribution of fos-like-immunoreactivity (fos-LI) in the medullary and upper cervical dorsal horn was examined following noxious facial stimulation, in order to evaluate the use of fos as a marker for neuronal activation in trigeminal nociceptive pathways. Control animals that received urethane anesthesia and no facial stimulation showed substantial bilateral labeling in the trigeminal complex that was restricted to one rostrocaudal level, at the transition between the medullary dorsal horn (nucleus caudalis) and nucleus interpolaris. Noxious mechanical stimulation (pinch) of different facial sites produced labeling in the ipsilateral dorsal horn whose distribution varied predictably with the rostrocaudal and dorsoventral position of the facial stimulation site, such that rostral facial sites were represented rostrally in the dorsal horn and dorsal sites were represented ventrolaterally. The cornea was exceptional among the facial stimulation sites in that it had a specific representation at two distinct rostrocaudal levels, in C1 and the interpolaris-caudalis transition region; the position of the rostral peak was somatotopically inappropriate, based on the representation of other facial sites. The proportion of labelling in laminae III-IV relative to laminae I-II was higher with noxious mechanical stimulation than with noxious thermal (55 degrees C) or chemical (subcutaneous injection of capsaicin) stimulation. The proportion of labelling in laminae III-IV produced by electrical stimulation of the infraorbital nerve was no greater than that produced by pinch. The results suggest that fos-LI mapping can be a useful method for the investigation of somatotopy but is subject to serious limitations when used for the investigation of laminar organization. The results also suggest that the interpolaris-caudalis transition region may have properties that are distinct from those of the rest of the trigeminal complex, possibly related to an involvement in autonomic function.

Fos expression in the medullary dorsal horn of the rat after chronic constriction injury to the infraorbital nerve.

Chronic constriction injury to the rat's infraorbital nerve (IoN-CCI) induces asymmetric face grooming directed to the injured nerve territory and, beginning at 7-12 days postoperative, hyperresponsiveness to mechanical stimulation in this territory (B.P. Vos, A.M. Strassman, and R.J. Maciewicz, 1994, J. Neurosci. 14:2708-2723). To examine central mechanisms involved in these behavioral alterations, changes in nonevoked and mechanical stimulation-evoked fos-like immunoreactivity (fos-LI) following IoN-CCI were quantified in the medullary dorsal horn. Following the appearance of hyperresponsiveness in IoN-CCI rats, experimental and matched sham-operated rats were anesthetized with urethane and received either no stimulation or repeated stimulation with either a 2- or 15-g von Frey hair applied to the hairy skin between vibrissae B3-4/C3-4 on the operated side. Unstimulated IoN-CCI rats had increased fos-LI in laminae I-IV of the ipsilateral medullary dorsal horn. In both groups, mechanical stimulation produced a distinct pattern of fos-LI in the ipsilateral medullary dorsal horn, the quantity of which was related to stimulus intensity. For both stimulus intensities, the total amount and the rostrocaudal spread of evoked fos-LI were significantly larger in IoN-CCI rats. In IoN-CCI rats, stimulation-evoked increases in fos-LI were proportionally larger in laminae I-II than in III-IV. This laminar effect was also present in sham-operated rats but only for 15-g stimulation. Neither condition nor stimulus intensity affected fos-LI in the contralateral medullary dorsal horn. Positive correlations were found between the behavioral parameters of increased trigeminal nociceptive activity and the total amount of fos-LI in the ipsilateral medullary dorsal horn. The results demonstrate that IoN-CCI induces significant alterations in the central processing of afferent signals, which may underlie behavioral manifestations of increased nociceptive activity.

Rat somatosensory cerebropontocerebellar pathways: spatial relationships of the somatotopic map of the primary somatosensory cortex are preserved in a three-dimensional clustered pontine map.

In the primary somatosensory cortex (SI), the body surface is mapped in a relatively continuous fashion, with adjacent body regions represented in adjacent cortical domains. In contrast, somatosensory maps found in regions of the cerebellar hemispheres, which are influenced by the SI through a monosynaptic link in the pontine nuclei, are discontinuous ("fractured") in organization. To elucidate this map transformation, the authors studied the organization of the first link in the SI-cerebellar pathway, the SI-pontine projection. After injecting anterograde axonal tracers into electrophysiologically defined parts of the SI, three-dimensional reconstruction and computer-graphic visualization techniques were used to analyze the spatial distribution of labeled fibers. Several target regions in the pontine nuclei were identified for each major body representation. The labeled axons formed sharply delineated clusters that were distributed in an inside-out, shell-like fashion. Upper lip and other perioral representations were located in a central core, whereas extremity and trunk representations were found more externally. The multiple clusters suggest that the pontine nuclei contain several representations of the SI map. Within each representation, the spatial relationships of the SI map are largely preserved. This corticopontine projection pattern is compatible with recently proposed principles for the establishment of subcortical topographic patterns during development. The largely preserved spatial relationships in the pontine somatotopic map also suggest that the transformation from an organized topography in SI to a fractured map in the cerebellum takes place primarily in the mossy fiber pontocerebellar projection.