Muscle insulin-like growth factor-I modulates murine craniofacial bone growth.

Insulin-like growth factor I (IGF-I) is essential for muscle and bone development and a primary mediator of growth hormone (GH) actions. While studies have elucidated the importance of IGF-I specifically in muscle or bone development, few studies to date have evaluated the relationship between muscle and bone modulated by IGF-I in vivo, during post-natal growth. Mice with muscle-specific IGF-I overexpression (mIgf1+/+) were utilised to determine IGF-I- and muscle-mass-dependent effects on craniofacial skeleton development during post-natal growth. mIgf1+/+ mice displayed accelerated craniofacial bone growth when compared to wild-type animals. Virus-mediated expression of IGF-I targeting the masseter was performed to determine if post-natal modulation of IGF-I altered mandibular structures. Increased IGF-I in the masseter affected the mandibular base plane angle in a lateral manner, increasing the width of the mandible. At the cellular level, increased muscle IGF-I also accelerated cartilage thickness in the mandibular condyle. Importantly, mandibular length changes associated with increased IGF-I were not present in mice with genetic inhibition of muscle IGF-I receptor activity. These results demonstrated that muscle IGF-I could indirectly affect craniofacial growth through IGF-I-dependent increases in muscle hypertrophy. These findings have clinical implications when considering IGF-I as a therapeutic strategy for craniofacial disorders.

Determining fitting ranges of various bone conduction hearing aids.

OBJECTIVES: To define fitting ranges for nine bone conduction devices (BCDs) over different frequencies based on the device's maximum power output (MPO) and to validate the assessment of MPO of BCDs in the ear canal. BACKGROUND: Maximum power output (MPO) is an important characteristic when fitting BCDs. It is the highest output level a device can deliver and is one of the major determinants of a device's fitting range. A skull simulator can be used to verify MPO of percutaneous BCDs. No such simulator is available for active and passive transcutaneous devices. DESIGN: The MPO of nine different BCDs was assessed either by real-ear measurements and/or with skull simulator measurements. MAIN OUTCOME MEASURES: MPO and cross-validation of the methods using the Bland-Altman method. RESULTS: Percutaneous BCDs have higher MPO levels compared to active and passive transcutaneous devices. This results in a wide dynamic range of hearing for percutaneous devices. Moreover, the assessment of MPO by real-ear measurements was validated. CONCLUSION: Based on MPO data, fitting ranges were defined for nine BCDs over seven frequencies.

Natural history and outcomes in drug-induced autoimmune hepatitis.

AIM: Drug-induced autoimmune hepatitis (DIAIH) remains poorly characterized. Our aim was to assess natural history and outcomes in DIAIH. METHODS: This was a retrospective cohort study. RESULTS: Eighty-two patients with autoimmune hepatitis (AIH) were identified, 11 (13.4%) with DIAIH, implicated drugs being nitrofurantoin (n = 4), statins (n = 4), herbal remedies (n = 2) and diclofenac (n = 1). Female sex, acute onset, elevated serum globulins/immunoglobulin G, fibrosis stage (Ishak), cirrhosis at onset, moderate-severe portal inflammation, interface and lobular hepatitis, remission, relapse and poor outcome were similar in those with DIAIH and AIH (P > 0.05). The former were however more likely to be aged 60 years or more and take longer to relapse on immunosuppression discontinuation (P = <0.05). On Kaplan-Meier analysis, probability of poor outcome was similar in those with DIAIH and AIH (log-rank test, 0.339). On comparing those with (n = 4) and without nitrofurantoin (n = 7) DIAIH, the former were older, had longer duration of drug use prior to DIAIH diagnosis, higher fibrosis stage and were less likely to relapse upon immunosuppression discontinuation. CONCLUSION: Approximately 15% of patients with AIH have DIAIH with similar outcomes, although the latter are older with a propensity for late relapse, mandating long-term follow up.

Is there an overlap between irritable bowel syndrome and appendicopathy syndrome? A new theory.

BACKGROUND AND AIMS: The costs of irritable bowel syndrome are huge - personally, socially and financially. Yet despite numerous articles on the subject, an effective treatment seems far away. The hypothesis to be offered in this paper is: that a (laparoscopic) appendicectomy could also be useful in treating at least some of the patients with IBS. Using data I have collected from my own surgery practice over a number of years, I will demonstrate the link between the effective treatment of appendicitis by laparoscopic appendectomy and propose that this could also be a useful treatment for some cases of IBS. The study of symptoms of IBS showed that it shared several of the symptoms found in appendicopathy. The aim of this study is: (1) to confirm the cure rate of the laparoscopic appendectomy in cases of appendicopathy, (2) to determine the overlap of symptoms and (3) examine a new theory - that some cases of IBS originate in the appendix. SUPPORTING DATA: Two succeeding series of patients sent to me for possible appendicopathy were treated with laparoscopic appendectomy if their list of symptoms suggested this was appropriate. The first series comprised 114 patients. The results prompted a second series of 126 patients. This second group was primarily set up to confirm the results obtained from the first group. In our material we found statistical evidence that both groups were comparable indeed. Both groups suffered from not only pain, but also other side effects: indigestion, problems with exercise, feelings of stress, defecation disorders, disuria and loss of energy. The favourable results of the second series were roughly the same as those of the first one. Not only were about 80% of the patients pain free after 6 months or less, but the co-morbidity was gone in about 80% of the patients as well. In the literature, there are several reports describing a favourable outcome of appendicectomy for appendicopathy. Especially positive was one of only a few randomised, double-blinded, placebo controlled, parallel group trials in the history of surgery (Roumen, cs), which proved that "persistent or recurrent lower abdominal pain can be treated by elective appendicectomy with significant pain reduction in properly selected cases". An important part of the symptoms of both syndromes do overlap: (1) pain in the abdomen, varying in strength and more pain after a large meal, (2) changing bowel habits between constipation and diarrhoea, (3) indigestion and (4) stress. CONCLUSION: Taking into account the overlap in several symptoms between IBS and Appendicopathy there is a possibility that both syndromes originate (partly) in the appendix and therefore laparoscopy and appendicectomy may play a part in the treatment of IBS as well. Pilot studies in this direction seem to be indicated.

Augmentation in anterior cruciate ligament reconstruction-a histological and biomechanical study on goats.

We studied reconstruction of the anterior cruciate ligament (ACL) in skeletally mature goats. In one group, the autogenous tissue was augmented with polydioxanone (PDS), the other group had no augmentation. Histological complete incorporation and remodeling of the transplant was found in both groups. The newly formed connective tissues gradually assumed the microscopic properties of the normal ligament. The augmented group showed a delay in remodeling and maturation of the fiber bundles. Mechanically, the PDS-augmented transplants were stronger than the nonaugmented transplants immediately after surgery. During the first 6 weeks, a rapid decrease in strength of the augmented transplants was found, whereas the strength of the nonaugmented group gradually increased. The results of our experiment do not favor augmentation of autografts in reconstruction of the ACL.

Monitoring of fetuses with intrauterine growth restriction: a longitudinal study.

OBJECTIVE: To describe the time sequence of changes in fetal monitoring variables in intrauterine growth restriction and to correlate these findings with fetal outcome at delivery. METHODS: This was a prospective longitudinal observational multicenter study on 110 singleton pregnancies with growth-restricted fetuses after 24 weeks of gestation. Short-term variation of fetal heart rate, pulsatility indices of fetal arterial and venous Doppler waveforms and amniotic fluid index were assessed at each monitoring session. The study population was divided into two groups: Group 1 comprised pregnancies with severely premature fetuses, which were delivered < or =32 weeks and Group 2 included pregnancies delivered after 32 completed weeks. Logistic regression was used for modeling the probability for abnormality of a variable in relation to the time interval before delivery. Trends over time were analyzed for all variables by multilevel analysis. RESULTS: Ninety-three (60 in Group 1 and 33 in Group 2) fetuses had at least three data sets (median, 4; range, 3-27) and had the last measurements taken within 24 h of delivery or intrauterine death. The percentage of abnormal test results and the degree of abnormality were higher in Group 1 compared to Group 2. Amniotic fluid index and umbilical artery pulsatility index were the first variables to become abnormal, followed by the middle cerebral artery, aorta, short-term variation, ductus venosus and inferior vena cava. In Group 1, short-term variation and ductus venosus pulsatility index showed mirror images of each other in their trend over time. Perinatal mortality was significantly higher if both variables were abnormal compared to only one or neither being abnormal (13/33 (39%) vs. 4/60 (7%); P = 0.0002; Fisher's exact test). CONCLUSION: Ductus venosus pulsatility index and short-term variation of fetal heart rate are important indicators for the optimal timing of delivery before 32 weeks of gestation. Delivery should be considered if one of these parameters becomes persistently abnormal.

Laparoscopic appendectomy: a new opportunity for curing appendicopathy.

It is strongly disputed whether the appendix is indeed the cause of chronic abdominal complaints, even when the pain is situated in the right lower quadrant. In 1976 the introduction of a new operative technique, the laparoscopic appendectomy, offered new insight by making it possible to remove an appendix that is not acutely inflamed through a second insertion in the right lower quadrant by using the open stump method. Between 1976 and 1989, this operation was performed on 1,214 patients in a regional population of about 75,000 people and was successfully performed in 85%. Two subgroups totaling 215 patients showed a success rate of greater than 80% with no major complications; after one year, the patients' scars were almost invisible. This high success rate of a somatic therapy for a so-called psychosomatic disease can be explained by the following possible pathological changes in the appendix: corpora aliena, parasites, kinking, adhesions, obliterations, viral follicular hypertrophy, fibrosis, and neural changes. Most of these conditions are postinfectious. The greater ability of female patients to handle infection results in differences between the two sexes in frequency, development, and behavior of the disease. Laparoscopy alone can reveal a herd of pathologic conditions in patients with pain of unknown origin. With the aid of the laparoscope, appendectomy can be added safely and more patients relieved from chronic abdominal complaints than previously thought possible.

A new technique for resecting the non-inflamed not-adhesive appendix through a mini-laparotomy with the aid of the laparoscope.

A new technique for appendicectomy is described. Following detailed laparoscopic inspection of the abdomen, the appendix is pulled out with a laparoscopic forceps through a small incision in the right lower abdomen; it is then skeletized. Following ligation with catgut and nylon, the appendix is severed using the thermocautery. The stump is subjected to careful after-coagulation or treated with iodine, and repositioned. Only the skin is sutured.