Evidence that preaxial polydactyly in the Doublefoot mutant is due to ectopic Indian Hedgehog signaling

Patterning of the vertebrate limb along the anterior-posterior axis is controlled by the zone of polarizing activity (ZPA) located at the posterior limb margin. One of the vertebrate Hh family members, Shh, has been shown to be able to mediate the function of the ZPA. Several naturally occurring mouse mutations with the phenotype of preaxial polydactyly exhibit ectopic Shh expression at the anterior limb margin. In this study, we report the molecular characterization of a spontaneous mouse mutation, Doublefoot (Dbf). Dbf is a dominant mutation which maps to chromosome 1. Heterozygous and homozygous embryos display a severe polydactyly with 6 to 8 digits on each limb. We show here that Shh is expressed normally in Dbf mutants. In contrast, a second Hh family member, Indian hedgehog (Ihh) which maps close to Dbf, is ectopically expressed in the distal limb bud. Ectopic Ihh expression in the distal and anterior limb bud results in the ectopic activation of several genes associated with anterior-posterior and proximal-distal patterning (Fgf4, Hoxd13, Bmp2). In addition, specific components in the Hedgehog pathway are either ectopically activated (Ptc, Ptc-2, Gli1) or repressed (Gli2). We propose that misexpression of Ihh, and not a novel Smoothened ligand as recently suggested (Hayes et al., 1998), is responsible for the Dbf phenotype. We consider that Ihh has a similar activity to Shh when expressed in the early Shh-responsive limb bud. To determine whether Dbf maps to the Ihh locus, which is also on chromosome 1, we performed an interspecific backcross. These results demonstrate that Dbf and Ihh are genetically separated by approximately 1.3 centimorgans, suggesting that Dbf mutation may cause an exceptionally long-range disruption of Ihh regulation. Although this leads to ectopic activation of Ihh, normal expression of Ihh in the cartilaginous elements is retained.     

Role of B.A. Petrov in foundation and development of free flap skin transplantation problem

The article reviews the history of development of free-flap skin transplantation and basic role of acad. B.A. Petrov who was the first to show the role of dermatom skin transplantation in vast granulating wounds as the only method saving the life of patients with severe burns. He also suggested to solve an actual problem--deficiency of resources of donor skin--by repeated excision of skin flaps from previously used donor sites and use of cadaver skin. Very important is ales the role of B.A. Petrov in development of such particular questions as the role of patient's condition, wound bed am microbial flora of the wound in survival of skin transplants. In aspect of historical relationships the perspective of new approach to treatment of deep burns by transplantation of ceratinocytes, cultivated outside the patient's organism is shown.     

Intrauterine vascular deficiency of the upper limb

We report six cases of intrauterine vascular deficiency of the upper limb, presenting over a 12-year period, with established areas of necrosis at the time of birth. Three of the six mothers were diabetic. An urgent examination of the neonate should be done to exclude occult systemic thomboses, as early anticoagulation or thrombolytic therapy may be indicated. The majority of cases were managed conservatively with dressings and splintage of the limb; exceptionally surgical intervention was required. Long-term sequelae included flexion contractures and shortening of the forearm bones.     

Retrospective and prospective analyses of the treatment of overanticoagulated patients

STUDY OBJECTIVE: To compare withholding warfarin therapy with low-dose (2.5 mg) oral vitamin K therapy in excessively anticoagulated patients without bleeding complications. DESIGN: Prospective and retrospective studies. SETTING: Anticoagulation clinic at a Veterans Affairs institution. PATIENTS: Twenty-eight men were matched according to initial international normalized ratio (INR) and INR goal ranges. INTERVENTIONS: The retrospective arm of the study consisted of chart reviews of overanticoagulated patients whose warfarin doses were held until therapeutic INR values were reached. The prospective arm included overanticoagulated patients who were administered a single 2.5-mg dose of oral vitamin K. MEASUREMENTS AND MAIN RESULTS: Mean days to therapeutic INR values were 2.3+/-0.6 and 1.4+/-0.6 (p=0.001), and mean reduction in INR 1 day after treatment intervention was 1.32+/-0.79 and 3.46+/-1.31 (p<001) U for the withholding and vitamin K groups, respectively. CONCLUSION: Compared with withholding the warfarin dose, administration of 2.5 mg of oral vitamin K to excessively anticoagulated patients receiving warfarin significantly reduced the time required to reach a therapeutic INR as well as final INR.     

Effect of guaiazulene on some cytochrome P450 activities. Implication in the metabolic activation and hepatotoxicity of paracetamol

The influence of timing of surgery in relation to menstrual period on survival of breast cancer patients has been both advanced advocated and disputed. A meta-analysis on published series showed a statistically significant overall odds reduction when surgery is performed in the luteal phase. The records of 165 premenopausal M- breast cancer women, not on hormonal therapies, consecutively operated on from 1977 to 1991 were reviewed. All patients underwent modified radical mastectomies or quadrantectomies plus operative radiotherapy, Node-positive patients received standard adjuvant chemotherapy. Cox regression analysis was used to estimate the relative risk (RR) of death in three models including timing of surgery, age, histology, pathological T and N. In each model, patients were divided into two groups according to the criteria proposed by Badwe, Hrushesky, and Senie. Multivariate analysis showed a significant association between pT and pN and survival, whereas no association with survival was observed for timing of surgery according to Badwe or Hrushesky or Senie criteria (RR = 1.26, RR = 0.91, and RR = 0.88 respectively). Up-to-date agreement on the menstrual phase and relative expected better prognosis is still lacking.     

The equine endometrial cup reaction: a review

The function of eCG in equine pregnancy is far from clear but it has become evident that eCG has little or no FSH activity in the horse and is therefore probably not responsible for the secondary ovulations. eCG does have luteotrophic activity and it could play a role in the resurgence of the primary corpus luteum (1,7,44). Some evidence exists that the receptor population on the equine gonads is heterogenous in a way that makes it possible to distinguish eCG from eLH, resulting in different post-receptor effects (7). There is also evidence that eCG itself is heterogenous, both in glycosylation and in primary structure, not only between different individual animals but also within one animal during different stages of gestation. The differences could simply reflect the difference between stored and secreted hormone, but on the other hand the release of different eCG forms could be under endocrine control, allowing the mare to produce forms appropriate to specific biological needs (74). Thus some forms of eCG could play a role in immunological events taking place at the foeto-maternal interface. The role of cytotoxic antibodies in the equine pregnancy is not understood. The fact that they are not harmful to the pregnancy can be explained by the fact that their target, the paternal MHC molecules, are withdrawn from the endometrial cup tissue by the time the antibodies start appearing in the circulation. This unique way of regulation of MHC expression is also poorly understood.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy

PURPOSE: To analyze the nonfatal adverse events (AE) associated with a first episode of status epilepticus (SE). METHODS: We performed a population-based retrospective cohort study to determine the morbidity of SE. Participants included 184 residents of Rochester, Minnesota who experienced nonfebrile SE between 1965 and 1984. RESULTS: The etiology of SE was acute symptomatic in 100 patients and unprovoked in 84 patients. The most common seizure-types were continuous partial (n=56, 30%), generalized convulsive (n=52, 28%), and generalized with focal features (n=32, 17%). Morbidity related to SE was noted in 5 of the 146 patients (3.4%) surviving 30 days. The AE included hemiparesis (n=3), encephalopathy (n=2), mental retardation (n=1), and aphasia (n=1). All patients with morbidity had an acute symptomatic (n=4) or remote symptomatic (n=1) etiology. Thirty-four patients (18.5%) had a second episode of SE. CONCLUSIONS: Based on this retrospective study, significant morbidity related to SE is uncommon and is associated with the underlying etiology.     

Use of polymerase chain reaction for identifying helminth DNA from the species Trichinella, Fasciola, Echinococcus, Nematodirus, Taenia

Primary care of girls between the ages of 10 and 20 presents some unique challenges. This article presents a review of normal adolescent development and explores preventive health issues and some of the more common acute medical problems of adolescent girls. Counseling on some behavioral and psychosocial issues also is discussed. Finally, anticipatory guidance topics to be discussed with parents are included.