Moderate superficial hypothermia prolongs bleeding time in humans.

BACKGROUND: In vitro and in vivo studies have shown that mild systemic hypothermia influences platelet adhesion and aggregation and coagulation reactions. We wanted to test the hypothesis that mild local hypothermia in healthy volunteers with preserved core temperature increased bleeding time. A secondary aim was to evaluate if local cooling influenced whole blood coagulation measured by thrombelastograph (TEG) in the same setting. METHODS: Bleeding time was measured at the left volar forearm at a baseline skin temperature of 32 degrees C and after cooling to 30 degrees C and 28 degrees C in a water bath. Skin temperature was continuously measured by contact thermistors. Measurements of coagulation by TEG were performed at baseline skin temperature before cooling and after cooling to 28 degrees C skin temperature. Tympanic membrane temperature was continuously measured. RESULTS: Compared with baseline, bleeding time was significantly prolonged at 30 degrees C skin temperature and further prolonged at 28 degrees C skin temperature. No significant differences were measured in any of the TEG parameters. During the procedure, tympanic membrane temperature did not change. CONCLUSION: Lowering the skin temperature from 32 degrees C to 30 degrees C and 28 degrees C with a preserved core temperature more than doubled the bleeding time. Whole blood coagulation measured by TEG was not influenced by the local cooling. In addition to core temperature, local temperature may offer information in understanding the surgical site of bleeding.

Nitric oxide production in the sphenoidal sinus by the inducible and constitutive isozymes of nitric oxide synthase.

OBJECTIVE: To study the production of nitric oxide (NO), and the presence of different isoforms of the NO-synthesising enzyme, NO-synthase (NOS), in the paranasal sinus. MATERIALS AND METHODS: Ten patients, undergoing surgery for pituitary adenoma, were examined for the presence of NO gas in the sphenoidal and maxillary sinus. The distribution of different NOS isozymes in mucosal biopsies from sphenoid and maxillary sinus and ethmoidal cells was studied. RESULTS: The mean concentration of NO was 2575 ppb in the sphenoidal sinus and 6792 ppb in the maxillary sinus. Morphological analyses revealed intense NADPH-diaphorase staining throughout the epithelium. Immunoreactivity against NOS2 (inducible NOS) was observed in the apical cell layer but not of the basal layer. NOS1 (neuronal NOS)-immunoreactivity was mainly seen in the subapical part of the epithelium and NOS3 (endothelial NOS)-immunoreactivity was observed only in the most apical part of the epithelium. CONCLUSION: NO concentration in the sphenoidal sinus is about the same as in the nasal cavity and approximately half of the concentration found in the maxillary sinus. All of the three main different isozymes of NOS can be demonstrated in the mucosa of the sphenoidal and maxillary sinus and ethmoidal cells, NOS2 being the most abundant isoform.

Nasopharyngeal glioma in a new-born girl.

Nasal gliomas are uncommon tumours of neurogenic origin that occur sporadically. They are diagnosed with MRI and a preoperative biopsy, and surgery is the treatment of choice. Most of the gliomas emerge from the nasal cavity, but only a few cases of nasopharyngeal gliomas have been reported. We present one case of a nasopharyngeal glioma and two cases of nasal gliomas.

Transsphenoidal adenomectomy in Cushing's disease via a lateral rhinotomy approach.

BACKGROUND: Cushing's disease may be treated by surgical pituitary adenomectomy. We present a surgical approach to the pituitary gland that increases the possibilities of a selective adenomectomy, and compare our results with those of other studies. METHODS: A retrospective study of patients with Cushing's disease undergoing transsphenoidal selective adenomectomy via a lateral rhinotomy at Sahlgrenska University Hospital from 1984-93 is presented. Thirty-one patients (26 women, five men; mean age: 44 years, range: 13-75 years) with Cushing's disease were followed for a median time of 4.5 years after operation (range: 1-10 years). Preoperative and postoperative urinary and serum cortisol, and circadian rhythm of serum cortisol were measured. We also measured serum TSH, T4, PRL, FSH, LH, and testosterone as well as urine and plasma osmolality. RESULTS: Our remission rate was 77% and the recurrence rate 3%. Hormonal insufficiency was rare. Hypothyroidism and hypogonadism were present in 3% of the patients, and diabetes insipidus occurred in 6% of the patients. CONCLUSION: Selective adenomectomy with its good opportunities for cure and improvement should be regarded as the treatment of choice for Cushing's disease. Using the lateral rhinotomy approach to the sphenoidal cavity results in good accessibility to the sella turcica and its pituitary adenomas, a low frequency of postoperative pituitary insufficiency, and a high remission rate.

Regenerating human nasal mucosa cells express peptide growth factors.

The goal of this study was to investigate if the distribution of peptide growth factors in the human nasal mucosa could be correlated to its maintenance and to repair processes. Biopsy specimens from clinically healthy humans, aged 6 months to 70 years, were investigated immunohistochemically. In the intact human nasal mucosa, only scattered basal epithelial cells and rare, randomly distributed cells in the lamina propria expressed peptide growth factor immunoreactivity. In contrast, in areas with deficient epithelial lining and infiltration of inflammatory cells, intense insulinlike growth factor I immunoreactivity was demonstrable in reactive epithelial cells, while adjacent, more differentiated cells were nonreactive. Vascular wall cells, fibroblasts, macrophages, and exocrine gland cells in the reactive nasal mucosa showed variable insulinlike growth factor I immunoreactivity and, at lower frequencies and intensities, immunoreactivity to insulinlike growth factor II, basic fibroblast growth factor, platelet-derived growth factor, and transforming growth factor beta, as did cells in the normally nonreactive exocrine glands. Macrophages and vascular smooth-muscle cells could in addition express platelet-derived growth factor immunoreactivity. Increased cell proliferation was recognized in reactive areas of the nasal mucosa specimens, ie, in those concomitantly showing distinct peptide growth factor immunoreactivity. We concluded that a complex pattern of peptide growth factor immunoreactivity is transiently expressed by reactive and regenerating nasal mucosal cells, contrasting with the nonreactive normal, differentiated cells. The close correlation between the appearance of peptide growth factors and the local repair and maintenance processes supports our working hypothesis that peptide growth factors are of functional importance for the nasal mucosa.

Transient expression of insulin-like growth factor I immunoreactivity by vascular cells during angiogenesis.

The present study was undertaken to investigate whether vascular cells show insulin-like growth factor I (IGF-I; somatomedin C) immunoreactivity under normal conditions and/or during angiogenesis in humans and animals, as the trophic peptide IGF-I is considered important for cell growth and differentiation. In adult animals normal blood vessels, i.e., arteries, veins, and capillaries, did not show any IGF-I immunoreactivity. In newborn animals every vascular cell showed IGF-I immunoreactivity; the frequency and intensity thereafter decreased and eventually vanished as the animals approached maturity. Injury of a tissue or organ rapidly induced extensive blood vessel formation and such new blood vessels transiently expressed IGF-I immunoreactivity. Endothelial cells in budding capillaries showed distinct cytoplasmic IGF-I immunoreactivity, as did endothelial cells, smooth muscle cells, and fibroblast in newly formed arteries and veins. In biopsies of human tissue, transient IGF-I immunoreactivity was evident in vascular cells during angiogenesis after injury, as it also was in granulation tissue, skin wounds, and scar capsules around implants. Increased IGF-I immunoreactivity was further demonstrated in vascular cells in biopsies from patients with other changes involving blood vessel formation, e.g., nasal polyps, and in specimens from patients with arteritis, tendonitis, synovitis, Wegener's granulomatosis, idiopathic midline destructive disease, neurofibromatosis (von Recklinghausen's disease), and muscular dystrophy. It is concluded that during angiogenesis, obviously irrespective of inducing factors and mechanisms, vascular wall cells transiently show IGF-I immunoreactivity.

Immunohistochemical demonstration of insulin-like growth factor I in inflammatory lesions in Wegener's granulomatosis and idiopathic midline destructive disease.

The immunoreactivity of the trophic peptide insulin-like growth factor I (IGF-I; somatomedin C) was mapped in nasal mucosa biopsies from three patients with Wegener's granulomatosis (WG) and one with idiopathic midline destructive disease (IMDD; idiopathic midline granuloma). Strongly increased IGF-I immuno-reactivity restricted to cells bordering and in vessel walls and in granulomas (WG) was demonstrated, while necrotic and noninflammatory areas were negative. Treatment with steroids and cyclophosphamide reduced the IGF-I immunoreactivity. The abnormally increased IGF-I immunoreactivities in WG and IMDD probably reflects the reactive growth processes in diseased tissue and is not thought to be the primary cause of either disease. IGF-I may be formed locally by cells in and close to the vascular walls in areas with active disease resulting in e.g. vascular growth, granuloma formation, and finally vessel obliteration and necrosis. IGF-I is likely to form, possibly in concert with other trophic factors, a link in the chain of events resulting in the tissue abnormalities in WG and IMDD.

Insulinlike growth factor I immunoreactivity in nasal polyps.

Nasal polyps from 15 patients were all found to express increased insulinlike growth factor I immunoreactivity. A hypothesis for the formation of nasal polyps is described: macrophages, seen in allergic and infectious reactions, produce and release growth factors, tentatively including insulinlike growth factor I. In enclosed paranasal sinuses this results in an accumulation of insulinlike growth factor I stimulating the growth of both epithelium and blood vessels in the sinuses. The mucosa increasingly bulges out through the ostium after having filled out the sinusity. Continuing growth stimulation is supplied by the inflammatory reaction, endothelial cells in the polyp, and activated macrophages inside or outside the polyp.

Transiently increased insulin-like growth factor. I. Immunoreactivity in UVB-irradiated mouse skin.

UVB-irradiation during 3 d for 90, 180, and 180 sec, respectively, at a daily dose of 0.1 and 0.2 joule/cm2, respectively, induced slight inflammatory reactions in the mouse ear. The insulin-like growth factor I (IGF-I) immunoreactivity, normally demonstrable only in scattered basal epidermal cells, rapidly increased in intensity and frequency in the epidermis. After 3 d of UVB irradiation almost all epidermal cells were outlined by IGF-I immunoreactivity in their plasma membrane. The Langerhans cells expressed intense IGF-I immunoreactivity throughout their cytoplasm. The elevated IGF-I immunoreactivity ceased after 5-7 d and was normalized in 3 weeks. The number of Ia positive epithelial Langerhans cells did not seem to be affected by UVB irradiation. It is concluded that the increased IGF-I immunoreactivity is likely to reflect formation of the trophic peptide IGF-I, most evidently by Langerhans cells, in early events of the inflammatory, reactive response of the skin to UVB irradiation.

Insulin-like growth factor I is a possible pathogenic mechanism in nasal polyps.

High concentrations of the trophic peptide insulin-like growth factor I (IGF-I; somatomedin C; SmC) were demonstrated immunocytochemically in all nasal polyps examined, except in areas with necrosis or tissue defects. Most epithelial cells, activated macrophages, and proliferating blood vessels, proved positive, contrasting with the low degree of cellular staining in adjacent normal nasal mucosa. It is proposed that nasal mucosal inflammatory reactions induce local formation and accumulation of IGF-I, which may eventually result in very high IGF-I concentrations in the paranasal sinuses due to the tendency these have to be enclosed, i.e. producing reduced drainage. Assuming that IGF-I constitutes the pathogenic factor, appropriate treatment should be given to reduce the inflammatory reactions and improve drainage.

Somatomedin C as tentative pathogenic factor in neurofibromatosis.

The distribution of somatomedin C (Sm-C; insulin-like growth factor I; IGF-I) immunoreactivity was examined in biopsies from three patients having the diagnosis neurofibromatosis established on clinical and histopathological criteria. All biopsies showed increased Sm-C immunoreactivity limited to areas with neurofibromas. Schwann cells, adjacent spindle-shaped fibroblast-like cells and newly formed blood vessels were positive. In addition, Sm-C immunoreactivity could be demonstrated in cells in the buccal epithelium. There was faint or no Sm-C immunoreactivity in biopsies from normal tissue of the patients and in specimens from control subjects. We propose that an abnormally increased local production of Sm-C, most likely by Schwann cells, forms a link in the chain of pathogenic events resulting in the disease neurofibromatosis.