Funding sources: German Research Foundation DFG, BONFOR programme of the Medical faculty of the University of Bonn. Conflicts of interest: None declared Dear Editor, The aetiopathogenesis of female pattern hair loss (FPHL) is poorly understood. Although research has strongly implicated genetic factors in familial occurrence,1 2 no association finding for FPHL has yet been replicated.3 4 5 Consequently, no causal biological pathways can be suggested on the basis of currently available genetic findings. A recent genome‐wide association study of ESR2 (oestrogen receptor 2) investigated 32 tag single‐nucleotide polymorphisms (SNPs) in an Australian FPHL sample and found nominal significance for three variants (rs10137185, rs17101774, rs2022748). The most significant SNP was rs10137185 (P = 0·003 for genotype CC versus genotypes CT + TT).6 This effect was consistent across subgroups stratified for disease severity and age‐at‐onset. Although no finding withstood experiment‐wide correction for multiple testing, the validity of the association with rs10137185 was supported by functional evidence from a public eQTL database, i.e. an association between the risk genotype CC and higher ESR2 expression levels in fibroblasts. This latter finding is consistent with reports that oestrogen has inhibitory effects on hair growth.7 In a previous study, we investigated four variants in the ESR2 gene in a U.K./German FPHL sample and found no association.5 However, this may have been attributable to the fact that none of these four variants were in strong linkage disequilibrium with variants showing association in the Australian sample (max. r2 = 0·149).
Summary. In this study the long‐term value of corrective osteotomy around the knee was evaluated by means of clinical and radiographic parameters. Between 1974 and 1984 we performed 52 corrective osteotomies in the vicinity of the knee on patients affected by haemophilic arthropathy. Forty‐two patients (45 osteotomies) were adequately followed‐up at an average 11.6 years postoperatively. Using the clinical score of the Advisory Committee of the World Federation of Haemophilia, 38 patients showed a postoperative improvement, five remained clinically unchanged and two showed deterioration. Range of motion of the knee joint did not significantly improve postoperatively. The radiographic Pettersson score showed only a marginal decrease by an average 0.003 points at the time of follow‐up. Only one patient needed subsequent joint replacement of both knees, on the left side 13 years after osteotomy and on the right side 8 years after osteotomy. Even in cases of marked radiographic joint destruction, corrective osteotomy shows acceptable long‐term clinical results, underlining the feasibility of this management option in the treatment of haemophilic arthropathy of the knee. Although moderate cartilage degenerations in the femoropatellar complex and in the contralateral compartment can be tolerated, this therapy should primarily be contemplated for those patients where damage is unicompartmental and a corresponding axial deviation is found. Particularly the younger patient can benefit from this treatment option in that joint replacement may possibly wholly be avoided or at least postponed to a later stage of life.
Since the middle of 1976 spinal and peridural anaesthesia are also being used for orthopaedic surgery of the lower extremities in haemophilic persons, the most important pre-requisites for the use of these techniques are: that it is a case of genuine haemophilia, that the deficiency is fully made up before and during anaesthesia and that the most important coagulation parameters are closely watched in co-operation with the Hemophilia Centre during the entire period. 46 haemophiliacs were given spinal and epidural anaesthesia via a catheter. A great advantage of these long-acting techniques is that less analgesics are needed during the postoperative period. Continuous peridural anaesthesia ensures freedom from pain without interfering with motoricity. The treatment of contractures of the joint by active and passive exercises has thus a better chance of success. Provided factors VIII/IX were kept normal there have so far not been any haemophilia-related haemorrhages into the spinal canal or cord or neurological disturbances that could be attributed to these anaesthetic techniques.
The retinal toxicity of single and repeated intravitreal injections of foscarnet was investigated. In addition, the effects of a combination of foscarnet and ganciclovir were studied, and a pharmacokinetic study to determine the ocular pharmacokinetics of foscarnet after intravitreal injection was carried out.Forty rabbits (both albino and pigmented) were used in this study. The electroretinographic (ERG) a-waves and b-waves and oscillatory potentials (OP) were used as as indicators of retinal toxicity. Potential toxicity was also assessed by ophthalmoscopy and histologic studies (light and electron microscopy).The a-wave and b-wave were not deteriorated with 2.4 mg foscarnet after single or repeated injections. The OP remained unchanged. There was no ERG change after intravitreal injection of a combination of both drugs. No evidence of retinal toxicity was observed by indirect ophthalmoscopy in any case. Light and electron microscopy on semithin sections of retina failed to demonstrate any adverse effects, and showed normal organization and cytoarchitecture of all the layers of the retina without evidence of cytopathology. The ocular pharmacokinetics of foscarnet determined by noncompartmental analysis showed a 34-hour terminal elimination half-life and an apparent volume of distribution of 1.9 ml.Based on these results, high doses of foscarnet were not judged toxic to the rabbit retina, with single or repeated injections. Moreover, concomitant injection of the two drugs did not induce any retinal toxicity. These findings suggest that when systemic treatment is to be stopped in patients with AIDS for toxic side effects, either ganciclovir or foscarnet may be used intravitreally as an alternative. Because a combination of the two drugs has been shown to be synergistic, both ganciclovir and foscarnet might be simultaneously injected into the vitreous cavity to block progression of cytomegalovirus retinitis.
