Proteus syndrome

The term Proteus syndrome was coined in 1983 to describe a disorder of skeletal, hamartomatous, and other mesodermal malformations. The syndrome was named after the Greek god Proteus, whose name means "the Polymorphous." Clinical features of this new syndrome are currently being defined. Including the case reported herein, we have found 34 patients with Proteus syndrome described in the English literature. Major clinical findings, defined as those findings seen in more than half of the cases, include hemihypertrophy, macrodactyly, exostoses, epidermal nevi, characteristic cerebriform masses involving the plantar or palmar surfaces, a variety of subcutaneous masses, and scoliosis. Histologic examination of subcutaneous masses has identified a variety of lipomatous, hamartomatous, and angiomatous tumors.     

Anaesthetic experience with paediatric interventional cardiology

Anaesthetic and sedation techniques, complications and outcomes were reviewed in 176 children undergoing 184 interventional cardiologic procedures. Techniques included sedation only, and ketamine, inhalational or narcotic anaesthesia. Ketamine infusion was the technique most frequently used. Ketamine was associated with a higher incidence of respiratory complications (P < 0.05) than the other techniques. The higher incidence of hypercarbia (15.6 per cent), which did not affect outcome, may be attributable to the use of supplemental sedatives. The incidence of upper airway obstruction (7.8 per cent) was similar to that of previous studies. Vascular compromise resulted from the procedure in 33 patients, necessitating surgical correction in 16. Cardiac perforation occurred in four cases, causing one death. Pulmonary valve stenosis was most amenable to balloon dilatation and aortic valve stenosis least amenable. Ketamine was the anaesthetic agent preferred by cardiologists for use in the catheterisation suite when general anaesthesia was required. Vigilant monitoring by anaesthetic staff is necessary during the procedure, and avoidance of concomitant narcotics is recommended if a ketamine technique with spontaneous ventilation is used. Les techniques anesthésiques et de sédation ainsi que les complications et les issues ont été revues chez 176 enfants subissant 184 procedures cardiaques. Les techniques ont inctu soil la sédation seulement, soit l’anesthésie à la kétamine, aux agents d’inhalation ou aux narcotiques. La perfusion de kétamine était la technique la plus fréquemment utilisée. La ketamine était associée à une plus grande incidence de complication respiratoire (P < 0.05) comparativement aux autres techniques. La plus grande incidence d’hypercarbie (15.6 pour cent), n’ayant pas affecté l’issue, pourrait être attribuée à l’utilisation additionnelle de sédatifs. L’incidence d’obstruction des voies aériennes supérieures (7.8 pour cent) était similaire aux études préalables. Un problème vasculaire suite à la procédure fut observé chez 33 patients dont 16 ont requis une correction chirurgicale. Une perforation cardiaque est survenue dans quatre cas provoquant le décès d’un seul patient. La sténose de la valve pulmonaire était la procédure la plus susceptible d’être dilatée et la sténose de la valve aortique la moins susceptible. La kétamine était l’agent anesthésique préféré par les cardiologistes lors des cathétérisations quand une anesthésie générate était requise. Une surveillance vigilante par une équipe anesthésique fut nécessaire durant la procedure. Il faut aussi éviter l’administration de narcotiques si la kétamine est administrée en respiration spontanée.

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Presented in part at the Canadian Anaesthetists’ Society annual meeting in Halifax, June 1988.     

Menstrual cycle and appetite control: implications for weight regulation

Hormonal fluctuations associated with the menstrual cycle influence appetite control and eating behaviour. Energy intake varies during the reproductive cycle in humans and animals, with a periovulatory nadir and a luteal phase peak. Patterns of macronutrient selection show less consistency but a number of studies report carbohydrate cravings in the premenstrual phase, particularly in women with premenstrual syndrome. The cyclical nature of food cravings are frequently, but not invariably, associated with depression. Fluctuations in appetite, cravings and energy intake during the menstrual cycle may occur in parallel with cyclical rhythms in serotonin, which can be accompanied by affective symptoms. The premenstrual phase can be considered as a time when women are especially vulnerable to overconsumption, food craving and depression; this is often associated with low serotonin activity.      

Expression of superoxide dismutase and xanthine oxidase in myometrium, fetal membranes and placenta during normal human pregnancy and parturition

Superoxide, an agent which attenuates the half-life of nitric oxide, is metabolized and synthesized by superoxide dismutase (SOD) and xanthine oxidase, respectively. Over the last few years much work has focused on the role of nitric oxide in human parturition. The aim of this study was to determine whether the onset of human parturition is associated with a change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were obtained from women before and after the onset of labour at term. Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like immunoreactivity was detected in syncytiotrophoblast cells, villous stromal cells and endothelial cells of blood vessels in the placenta. In the myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial cells and to some vascular smooth muscle cells. In the fetal membranes we observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion, extravillous trophoblast and decidua. There was no difference in SOD enzyme activity or staining intensity for SOD between different cell types before and during labour. Xanthine oxidase immunoreactivity was identified in each of the tissues examined and again there was no difference in immunostaining in tissues obtained from women delivered before or after the onset of labour. These results show that the pregnant uterus is capable of both synthesizing and degrading superoxide and suggest that superoxide dismutase and xanthine oxidase may play a role in the maintenance of uterine quiescence during pregnancy, but not in the initiation of parturition.      

Keratinocyte growth factor is an important endogenous mediator of hair follicle growth, development, and differentiation. Normalization of the nu/nu follicular differentiation defect and amelioration of chemotherapy-induced alopecia.

The growth and development of hair follicles is influenced by a number of different growth factors and cytokines, particularly members of the fibroblast growth factor (FGF) family. Keratinocyte growth factor (KGF or FGF-7) is a recently identified 28-kd member of the FGF family that induces proliferation of a wide variety of epithelial cells, including keratinocytes within the epidermis and dermal adnexa. Because KGF induces marked proliferation of keratinocytes, and both KGF and KGF receptor (KGFR) mRNA are expressed at high levels in skin, we sought to localize KGF and KGFR in skin by in situ hybridization. KGFR mRNA was relatively strongly expressed by keratinocytes in the basilar epidermis as well as throughout developing hair follicles of rat embryos and neonates. KGF mRNA was expressed at lower levels than was KGFR but could be localized to follicular dermal papillae in rat embryos and neonates. These results prompted us to investigate the effects of KGF on hair follicles in two distinct murine models of alopecia. In the first model, recombinant KGF (rKGF) induced dose-dependent hair growth over most of the body in nu/nu athymic nude mice when administered intraperitoneally or subcutaneously over 17 to 18 days. When administered subcutaneously, rKGF induced the most extensive hair growth at the sites of injection. Histologically, rKGF induced marked follicular and sebaceous gland hypertrophy, a normalization of the nu/nu follicular keratinization defect, and an increase in follicular keratinocyte proliferation as assessed by bromodeoxyuridine labeling. In the second model, a neonatal rat model of cytosine arabinoside chemotherapy-induced alopecia in which interleukin-1, epidermal growth factor, and acidic FGF have all demonstrated some degree of alopecia cytoprotection, rKGF induced a dose-dependent cytoprotective effect, abrogating as much as 50% of the alopecia in this model when administered beginning 1 day before the onset of chemotherapy. Taken together, these data suggest that KGF is an important endogenous mediator of normal hair follicle growth, development, and differentiation.     

Hydrosalpinges adversely affect markers of endometrial receptivity

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.      

Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers.

The oncoprotein encoded by bc1-2 is unique because of its intracellular location (a mitochondrial membrane protein) and apparent mode of action (suppression of apoptosis). To date, this oncogene has been associated only with the development of certain forms of human B-cell lymphoma. In this report, we describe our experience with a monoclonal antibody made against a synthetic peptide for bc1-2 that can recognize the bc1-2 protein and identify cells in human prostate glands expressing this proto-oncogene with in situ immunohistochemical procedures. These procedures were utilized to survey a series of 62 human tissues to evaluate whether bc1-2 might have a role in the developing prostate gland or in prostate oncogenesis. While all primordial epithelial cells in a fetal prostate gland immunostain for bc1-2, normal and hypertrophic prostate glands of the adult show bc1-2 expression restricted to the basal cells. All epithelial cells in areas of prostatic intraepithelial neoplasia were stained by this antibody, as were most (62%) localized invasive prostatic carcinomas. In contrast, all primary prostatic carcinomas and metastases obtained from metastatic prostate cancer patients after hormone treatment (hormone-refractory tumors) stained positive for bc1-2. This study demonstrates that the oncoprotein encoded by bc1-2 can be detected at sequential stages in the natural history of human prostate cancer. Since the bc1-2 oncoprotein is known to suppress the cellular response to apoptotic stimuli, it will be important to determine whether bc1-2 expression is a factor in the development of prostate cancers and in the survival of hormone-refractory prostate cancer cells.