Mapping the rat somatosensory pathway from the anterior cruciate ligament nerve endings to the cerebrum

The anterior cruciate ligament (ACL) serves as the primary restraint to anterior tibial translation. In addition to this biomechanical function, the ACL appears to have a function in neuromuscular control. This hypothesis was formulated after the discovery of mechanoreceptors within the ACL. The full somatosensory pathway from the ACL to the cerebrum has yet to be elucidated. In order to map this sensory pathway, we conducted a viral trans-synaptic tracing experiment using the neurotropic pseudorabies virus (PRV). The pseudorabies virus was injected into the ACL of rats and allowed to replicate and spread trans-synaptically for 6-7 days. The brain and spinal cord of each sacrificed rat was then removed and processed immunohistochemically to detect the presence of PRV. PRV-immunoreactive neurons were found to be localized in several different regions from the spinal cord to the cerebrum. Four nuclei in the reticular formation of the brain stem demonstrated strong positive labeling: the mesencephalic reticular nucleus, magnocellular reticular nucleus, paragigantocellular reticular nucleus, and gigantocellular reticular nucleus. This finding suggests that the nerve endings of the rat ACL project into the cerebrum and that the reticular formation may play an important role in the afferent pathway of those nerve endings.     

Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children

The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.     

Comparison of functional results with navigation-assisted minimally invasive and conventional techniques in bilateral total knee arthroplasty.

This study was undertaken to compare the clinical and radiological results achieved using navigation-assisted minimally invasive surgery (NA-MIS) and conventional (CON) techniques in 42 bilateral total knee arthroplasty (TKA) patients with a minimum follow-up of one year. Clinical evaluations were performed using range of motion (ROM), Hospital for Special Surgery (HSS) scores, and Western Ontario and McMaster University (WOMAC) scores (pain, functional, and total) at 3, 6 and 9 months and one year postoperatively. Patients' subjective preferences and radiological indices, including mechanical axis and coronal inclinations of the prostheses, were compared at one year postoperatively. NA-MIS TKA yielded better HSS and WOMAC total scores than CON TKA up to six months, and a better WOMAC pain score up to 9 months. However, these differences were not significant at one year postoperatively. ROM was comparable in both groups at all times, but more patients preferred the NA-MIS side to the CON side. Radiological results showed no differences in mean values between the two surgical groups, although the NA-MIS group contained fewer outliers than the CON group. In conclusion, NA-MIS TKA was associated with better clinical results up to 6 or 9 months after surgery, giving more accurate leg alignment than CON TKA.     

Outcome of and prognostic factors for decompressive hemicraniectomy in malignant middle cerebral artery infarction.

Decompressive hemicraniectomy as an appropriate treatment for malignant middle cerebral artery (MCA) infarction is still a controversial issue. This study aimed to determine the survival rate and functional outcome, and factors associated with these, in patients with malignant MCA infarction. From January 2000 to December 2003, 60 patients with malignant MCA infarction were treated in our hospital. All patients in the study underwent a large ipsilateral craniectomy and duroplasty for decompression. The infarction territory was evaluated by either diffusion weighted magnetic resonance imaging or computed tomography. Clinical neurological presentation was evaluated using the Glasgow Coma Scale. Functional outcome was evaluated using the Barthel index (BI) and the Glasgow Outcome Scale (GOS) at follow-up 12 months later. Thirty-day mortality was 20% (12 patients) and 12-month mortality was 26.6%. The factors associated with higher mortality were age>or=60 years, involvement of more than one vascular territory, presence of signs indicating clinical herniation before surgery, and treatment more than 24 hours after ictus. The mean GOS score was 3.3+/-1.7. The mean Barthel index was 65.1+/-40.1. Twenty-nine (65.9%) patients had a favourable outcome (BI>or=60). The factors associated with favourable outcome were age<60 years and treatment within 24 hours of ictus, before clinical signs of herniation were noted. Decompressive hemicraniectomy should be performed in patients younger than 60 years within 24 hours of ictus before clinical signs of herniation develop. Age, timing of surgery and clinical signs of herniation are prognostic factors for mortality and functional outcome.     

Endocrinology: Intravenous albumin does not prevent the development of severe ovarian hyperstimulation syndrome in an in-vitro fertilization programme

A cohort study was undertaken to compare the effect at the timeof oocyte retrieval of the i.v. administration of either 1000ml of lactated Ringer' solution or 1000 ml of a 5% solutionof human albumin on in-vitro fertilization patients at riskfor severe ovarian hyperstimulation syndrome (OHSS). A totalof 207 patients with an oestradiol concentration > 10 000pmol/l and/or > 15 follicles (>10 mm diameter) on theday of human chorionic gonadotrophin (HCG) injection were reviewed.Of these, 158 women received 500 ml of lactated Ringer’ssolution both before and after egg retrieval, and 49 women receivedtwo infusions of 500 ml of 5% human albumin in normal salineat the time of egg retrieval. Severe OHSS developed in two patientswho received human albumin and in 10 women who did not receivethe albumin. This difference was not statistically significant.There were no differences between the two groups in terms ofage, number of follicles punctured at transvaginal oocyte retrievalor oestradiol concentration at the time of HCG injection. Theadministration of a 5% human albumin solution does not preventthe development of severe OHSS in at risk patients. It doesappear to blunt the severity of the condition.     

15N nuclear magnetic resonance studies on the tautomerism of 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and other C8-substituted guanine nucleosides

The favored tautomeric and ionic structures were examined for the oxidative DNA damage adduct 8-hydroxy-2'-deoxyguanosine and its RNA analogue 8-hydroxyguanosine by 15N NMR spectroscopy. In addition, 15N chemical shifts and coupling constants from 13 different guanine nucleosides, including a wide variety of C8 substitutions (OH, SH, Br, OCH2C6H5, OCH3, SCH3, and SO2CH3), have been analyzed with respect to their tautomeric structures. A -98.5-Hz proton-nitrogen coupling constant observed for the N7 resonance of 8-hydroxyguanosine in dimethyl sulfoxide was evidence for 8-keto substitution, which is contrary to the structure implied by the generally used nomenclature. The pH dependence of 15N NMR spectra of 8-hydroxyguanosine in aqueous solution showed downfield shifts of the N1 and N7 resonances that were greater than 50 ppm, which indicated the conversion from a neutral 6,8-diketo to a 6-enolate-8-keto (pKa1 = 8.6) and finally to a 6,8-dienolate structure (pKa2 = 11.7). There was no evidence of an 8-enol substituent in the absence of ionization. It is proposed that the syn conformation of these oxidized bases in duplex DNA and RNA can be further stabilized by abnormal hydrogen bonding or mispairing that involves N7-H. The combined data show that 15N NMR is a sensitive probe to examine tautomerism of the guanine ring system. The analysis indicates that the change from a single to a double bond for the C8 substituent, and the accompanying removal of the normal double bond between N7 and C8 on the imidazole ring system, has no detectable effect on the tautomerism at the N1-O6 site of the pyrimidine ring system for both the 8-keto and 8-thio substitutions. In addition, large differences in electronegativity of the C8 substituents do not alter the N1-O6 tautomerism.     

Department of law and ethics

The January 7, 1988 issue of The New England Journal of Medicine has two interesting articles concerning what might generally be termed euthanasia. The article titled Initiating and Withdrawing Life Support represents a consensus among members of the Stanford University Medical Center Committee on Ethics. Its main authors have written a fine example of applied ethics (1).