J.W. van Neck

Generation of antisera to mouse insulin-like growth factor binding proteins (IGFBP)-1 to -6: comparison of IGFBP protein and messenger ribonucleic acid localization in the mouse embryo.

The insulin-like growth factor (IGF) system is an important regulator of fetal growth and differentiation. IGF bioavailability is modulated by IGF binding proteins (IGFBPs). We have generated six different antisera, directed to synthetic peptide fragments of mouse IGFBP-1 through -6. The specificity of the produced antisera was demonstrated by enzyme-linked immunosorbent assay, Western blotting, and by immunohistochemistry on sections of mouse embryos of 13.5 days post coitum. Specificity for the IGFBP-2 through -6 antisera also was confirmed immunohistochemically in liver and lung of corresponding gene deletion (knock-out) mutant mice and wild-type litter mates. Immunohistochemistry and messenger RNA (mRNA) in situ hybridization on sections of mouse embryos of 13.5 days post coitum revealed tissue-specific expression patterns for the six IGFBPs. The only site of IGFBP-1 protein and mRNA production was the liver. IGFBP-2, -4, and -5 protein and mRNA were detected in various organs and tissues. IGFBP-3 and -6 protein and mRNA levels were low. In several tissues, such as lung, liver, kidney, and tongue, more than one IGFBP (protein and mRNA) could be detected. Differences between mRNA and protein localization were extensive for IGFBP-3, -5, and -6, suggesting that these IGFBPs are secreted and transported. These results confirm the different spatial localization of the IGFBPs, on the mRNA and protein level. The overlapping mRNA and protein localization for IGFBP-2 and -4, on the other hand, may indicate that these IGFBPs also function in an auto- or paracrine manner. (Endocrinology 140: 5944 ‐5952, 1999)

Gene Expression of the Insulin-Like Growth Factor System During Postnatal Development of the Rat Pituitary Gland

Insulin‐like growth factors I and II (IGFI and II) are synthesized by anterior pituitary cells and participate in cellular growth and differentiation, as well as the control of pituitary hormone secretion. Type 1 and 2 IGF receptors (IGFR1 and IGFR2) and the six IGF binding proteins (IGFBPs), which modulate IGF effects, are expressed in the anterior pituitary gland. We used in situ hybridization to analyse the temporal expression pattern of IGFI and II, IGFR1 and 2 and IGFBP1–6 in the anterior pituitary gland during postnatal development in both male and female rats (10, 20, 30, 40 and 60 days of age). We found all of the components of the IGF system to be expressed in the anterior pituitary gland, with each having a specific temporal pattern of expression. In addition, there exist differences between the sexes in the expression of some components of the IGF system. These data emphasize that in the anterior pituitary gland the IGF system is under tight regulation during postnatal life when this gland continues to develop. The distinct temporal expression of each member of the IGF system may indicate specific roles in the development and physiology of the anterior pituitary gland.

The incidence of symptomatic neuroma in amputation and neurorrhaphy patients

PURPOSE The incidence of symptomatic neuroma in finger nerve injuries varies widely in the literature. In this retrospective study, we evaluated the incidence of symptomatic neuroma after repair of digital nerve injuries (neurorrhaphy) and after amputation of one or more fingers. We also determined the need for re-operation on symptomatic neuroma patients. METHODS In a retrospective study, we collected data from medical files. All patients who were treated for a hand trauma in the emergency department during the last 10 years were included. We gathered data on the presence of symptomatic neuroma and re-operation of the patients. RESULTS In our database, 583 people had a peripheral nerve injury of whom 177 people had an amputation. The incidence of digital nerve injury without amputation followed by neurorrhaphy was 1%. In digital nerve injuries with amputation the incidence was 7.8%, which is significantly higher than after digital nerve injuries without amputation. CONCLUSIONS People with an amputation injury have significantly more symptomatic neuroma than people who undergo neurorrhaphy. People who have a symptomatic neuroma after digital nerve injuries have been operated significantly more than people who have a non-symptomatic neuroma or no neuroma at all. This information can be of help when treating digital nerve injuries. TYPE OF STUDY/LEVEL OF EVIDENCE (LOE): Prognostic.

Linear Mandibular Measurements: Comparison between Orthopantomograms and Lateral Cephalograms:

Objective: To investigate the reliability of length measurements of the mandible by comparing orthopantomograms (OPTs) with lateral cephalograms. Design: Observational study. Setting: OPTs and lateral cephalograms were taken of 20 human dry skulls. Four orthodontists and four maxillofacial surgeons located landmarks on all radiographs using a computer program for cephalometric measurements. Intraobserver and interobserver variability in locating landmarks was assessed, as well as positioning of the skulls prior to radiography between the x-ray assistants. Magnification differences between the left and right side of the mandible on the OPT were determined for five skulls. Kappa statistics were used to calculate the intraclass correlation coefficient for intraobserver and interobserver differences. An F test was used to assess differences between methods and between type of observer. Results: No significant differences were found in the magnification factor of the left and right side of the mandible. Compared with a lateral cephalogram, the OPT had comparable reliability in measuring mandibular distances condylion-gonion, gonion-menton, and condylion-menton. No significant differences were observed between the x-ray assistants in taking the OPTs and lateral cephalograms or in repositioning the skulls. Significant differences were found between orthodontists and maxillofacial surgeons for landmark measurements. Conclusion: An OPT is as reliable as a lateral cephalogram for linear measurements of the mandible (condylion-gonion, gonion-menton, and condylion-menton).

Systematic review of treatments for diabetic peripheral neuropathy

To evaluate treatment options for neuropathic pain and sensory symptoms resulting from diabetic peripheral neuropathy of the feet.

Histomorphometric comparison between continuous and discontinuous distraction osteogenesis

INTRODUCTION Experimental research on optimising the distraction protocol has been performed extensively in the past. However, relatively little research has been done on the rhythm of distraction. Findings in the orthopaedic literature showed that the outcome of distraction osteogenesis (DO) is positively influenced by increasing the rhythm of distraction. The aim of this study is to quantitatively compare continuous with discontinuous rhythms of distraction in rabbits. MATERIALS AND METHODS Tissue blocks of regenerated bone were harvested from thirty-eight young adult female New-Zealand White rabbits. After a latency period of three days, rabbits were subjected for eleven days to either single daily activation of the distractor at a rate of 0.9 mm/d, or triple daily activation at a rate of 0.9 mm/d, or continuous activation at a rate of 0.9 mm/d. After three weeks of consolidation, bone regenerates were analysed using histomorphometry. RESULTS The continuous DO group showed significantly (p<.01) more regenerate bone volume in the central part of the regenerate than the discontinuous DO groups. Higher osteoblastic activity was seen, as well as more blood vessels (p<.05). Bone volume and the number of blood vessels correlated significantly in the central part of the regenerate (p<.05). Also, the early mineral apposition rate (MAR) was higher than the late MAR (p<.05). CONCLUSIONS Continuous DO significantly accelerates bone formation when compared with discontinuous DO.

Changes of mandibular ramal height, during growth in unilateral hemifacial microsomia patients and unaffected controls

The aim of this study was to design mandibular ramal height growth curves for patients with HFM and compare those with the curves for a Dutch reference population. Two hundred fifty-one pre-operative orthopantomograms (OPTs) from 84 patients with unilateral HFM were used in conjunction with a control set of 2260 OPTs from 329 healthy individuals from the Nijmegen Growth Study (NGS) to determine mandibular ramal distances. For grades I/IIa and IIb/III, and for both sides, growth curves were constructed for mandibular ramal height with a linear curve-fitting procedure. This procedure revealed a significant difference between HFM patients and the NGS control group (p < 0.001); both in the mild and severe group mandibular ramal height differed significantly between the affected and non-affected side (p < 0.001). Growth was similar between HFM patients and the NGS control group. HFM patients therefore start with a smaller mandible and end with a smaller mandible, but experience growth similar to the Dutch normal population. These growth curves may aid the timing and determination of the combined surgical orthodontic treatment plan for HFM patients.

Rabbits as a model for research into craniofacial distraction osteogenesis

Various factors affect the choice of the appropriate animal for craniofacial research. We have evaluated the rabbit as a suitable animal for research on craniofacial distraction osteogenesis. We describe our experience with housing and handling them, surgical and experimental protocols, and compare them with other animals. We introduce, and describe the use of, a continuous hydraulic distractor on the nasal bones of the rabbit. Fifty-two skeletally mature New Zealand White rabbits were used. Forty-two of the 52 operations were uneventful. Ten of the fifty-two developed complications, of which two were animal-related, and the other eight distractor-related. During the experiments the animals stayed healthy, and the distraction procedures were well tolerated. Rabbits are excellent for use in biological research on craniofacial distraction osteogenesis. Specifically, their nasal bones are easily accessible, the size and shape of the nasal bones allow various commercially available as well as custom-made distractors to be attached to the bones easily, their care and housing are relatively simple and inexpensive, and harvesting of tissue for further analyses is no problem because their skulls are of a manageable size and shape compared with other laboratory animals.

The IGF‐I/IGFBP system in congenital partial lipodystrophy

Insulin and IGF‐I interact at many levels. Little is known about the insulin‐like growth factor‐I/insulin‐like growth factor binding proteins (IGF‐I/IGFBP) system in congenital partial lipodystrophy, a syndrome characterized by insulin resistance, hyperinsulinaemia and absence of truncal and limb fat. Some cases have acromegaloid features with thick skin and large hands and feet in association with normal levels of circulating growth hormone.

Ultrasound-guided needle positioning near the sciatic nerve to elicit compound muscle action potentials from the gastrocnemius muscle of the rat

The use of ultrasound-guided electrode positioning in near-nerve myography was investigated. This is a minimally invasive technique that allows repeated measurements to increase accuracy and hence decreases animal numbers. Ultrasound imaging of the sciatic nerve was performed in nine rats using a 55 MHz high-end transducer. Once visualised, a monopolar needle electrode was placed through the skin near this nerve. Upon stimulation, two surface electrodes, placed over the gastrocnemius muscle, recorded compound muscle action potentials (CMAPs). Reproducibility was tested having two teams of investigators perform the recordings consecutively. Reliability of the procedure was determined by comparing the ultrasound method to the conventional technique, which requires an incision through muscle and skin to expose the sciatic nerve. In all animals the sciatic nerve was visible on ultrasound images. Both methods showed CMAP latencies (duration was determined as the time interval between the onset latency and positive peak). The conventional method had a mean latency of 3.4±0.5 ms, our method had a mean latency of 3.3±0.5 ms. Reproducibility was excellent (observed latencies and amplitudes: 3.3 versus 3.3 ms and 25.6±5.1 mV versus 22.5±8.8 mV) resulting in a coefficient of variation for duration of 2.1% and for amplitude 6.7%. Interclass correlation coefficient was 0.828 for duration. Comparing the three different measurements no significant differences were found and our new method can therefore be considered reliable and comparable to the conventional method. Ultrasound-guided near-nerve needle positioning is a reproducible and reliable minimally invasive method for selectively eliciting CMAPs, which allows repeated CMAP measurements for studying nerve regeneration in rats.