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Abstract Background Preliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function. There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response. The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules. Results Between 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given. SIB radiation schedules with 5–6 × 2 Gy/week to 60–70 Gy, 5 × 2.2 Gy/week to 66–68.2 Gy (according to the RTOG protocol H-0022), or 5 × 2.11 Gy/week to 69.6 Gy were used. After mean 18 months (10–44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session. Conclusion SIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to tumor response and tolerance. SIB with 2.2 Gy is not recommended for large tumors involving laryngeal structures.

Background: Preliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function. There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response. The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules. Results: Between 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given. SIB radiation schedules with 5-6 × 2 Gy/week to 60-70 Gy, 5 × 2.2 Gy/week to 66-68.2 Gy (according to the RTOG protocol H-0022), or 5 × 2.11 Gy/week to 69.6 Gy were used. After mean 18 months (10-44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p <0.01), and in definitive (43 cc) vs postoperative IMRT (25 cc, p <0.05); the locoregional failure rate was twofold higher in definitively irradiated patients. Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session. Conclusion: SIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to tumor response and tolerance. SIB with 2.2 Gy is not recommended for large tumors involving laryngeal structures. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the general light and electron microscopic findings which lend support to the histopathologic diagnosis of the main cutaneous manifestations of Lyme borreliosis. The diagnostic criteria are delineated and illustrated. In culminating lesions of erythema migrans and acrodermatitis chronica atrophicans, a peculiar connective tissue reaction includes an increase in the number of fibroblasts, proliferation of collagen fibres and interstitial mucinous oedema. The cellular infiltrates are patchy and perivascular in erythema migrans and either patchy and/or band-like and interstitial in acrodermatitis chronica atrophicans. They consist of lymphohistiocytic cells with a variable admixture of plasma cells. The damage to elastic (and even collagen) fibres occurs in early acrodermatitis chronica atrophicans and is reflected by the phenomenon of elastophagocytosis with a fragmentation of elastic and oxytalan fibres. Reduction of the number or lack of pilosebaceous units is a constant finding. In advanced lesions of acrodermatitis chronica atrophicans a thinning of the dermal breadth is noticed, resulting from a decrease of collagen and elastic fibres. Fibrous nodules and morphea-like conditions are characterized by excessive formation of collagen. Borrelial lymphocytoma exhibits two different patterns of infiltration, accompanied by dermal fibrosis and increased numbers of fibroblasts. Recent tick bites show a predominantly neutrophilic infiltrate, with an admixture of eosinophilic granulocytes. By applying the results of this synoptic study, histopathologic diagnosis including the histological and ultrastructural findings of cutaneous borrelia infections should be possible without the absolute necessity of clinical correlation. [ABSTRACT FROM AUTHOR]

In women with endometriosis, the peristaltic activity of the uterus is significantly enhanced and may even become dysperistaltic at midcycle. Since uterine peristalsis is confined to the endometrium and the subendometrial myometrium with its predominantly circular arrangement of muscular fibres it was assumed that this dysfunction might be associated with structural abnormalities that could be visualized by high resolution ultrasonography and magnetic resonance imaging (MRI). Therefore, the uteri of women with and without endometriosis were subjected to endovaginal sonography (EVS) and to MRI. In EVS, women with laparoscopically proven endometriosis and infertility exhibited an infiltrative expansion of the archimetra in that the halo surrounding the uterine endometrium and representing the subendometrial myometrium was significantly enlarged compared with controls. The expansion was more pronounced in older than in younger women. There was, however, no relationship between the width of the expansion and the severity of the endometriotic disease. Similar data were obtained by MRI in that the `junctional zone' in women with endometriosis and infertility was expanded in comparison with controls. The results of this study provide further support to the notion that endometriosis is primarily a uterine disease. [ABSTRACT FROM PUBLISHER]

Immunocytochemistry of oestrogen receptor (ER) and progesterone receptor (PR) expression of the whole uterine muscular wall and the endometrium was performed in order to obtain morphological and functional insights into the regulation of cyclic uterine peristalsis, which is confined to the endometrium and the subendometrial myometrium and serves functions such as rapid and sustained sperm transport. The study revealed that the subendometrial myometrium or stratum subvasculare with a predominantly circular arrangement of muscular fibres exhibits a cyclic pattern of ER and PR expression that parallels that of the endometrium, whereas the outer portion of the uterine wall composed of the stratum vasculare and supravasculare, which represents the bulk of the uterine musculature, does not exhibit a cyclic pattern of ER and PR expression. According to ontogenetic and phylogenetic data from the literature, the outer myometrium is of non-paramesonephric origin with functions confined to parturition, while the inner myometrial layer together with the glandular epithelium and the stroma of the endometrium is of paramesonephric origin with various functions during the cycle in addition to those during pregnancy and parturition. The inner quarter of the stratum vasculare adjacent to the stratum subvasculare constitutes a transitional zone in that the cyclicity of receptor staining becomes, in radial direction, gradually less expressed. Morphologically this zone corresponds to the inner part of the stratum vasculare where its muscular fibres blend with those of the stratum subvasculare. [ABSTRACT FROM PUBLISHER]

Leaves of 12‐week‐old tobacco plants (Nicotiana tabacum L. cv. Samsun NN) were infiltrated with suspensions of Pseudomonas syringae pv, pisi (DSM 50291) to induce hypersensitive reaction (HR). Cotyledons of 2‐week‐old cotton plants (Gossypium hirsutum L. cv. Acala 442 and Coker BR) were infiltrated with Xanthomonas campestris pv. malvacearum (race 10) to induce the disease. In tobacco, HR‐related increases in NH+4 levels started within 2 h after infection and continued up to the time of tissue decay. Increase of NH+4 and especially K+ efflux were detected in intercellular washing fluids (IWF). Antibiotics stopped and later reverted NH+4 production and K+ efflux, but only if applied within 2 h after infection. When 10 mM NH+4 was injected into leaves, it was rapidly consumed from the IWF, and also, although more slowly, within the leaf cells. The concomitant K+ efflux was strong but delayed, and most of the K+ was reabsorbed after 2 h. Bacterial cell multiplication in HR stopped before the appearance of HR symptoms and cell necrosis. In the compatible reaction in cotton cotyledons, both NH+4accumulation and K+ efflux proceeded much more slowly than in the HR with tobacco, and bacteria continued to multiply until general cell necrosis occurred. The compatible reaction developed faster in constant darkness than in a light/dark rhythm. Bacterial enzymes produced NH+4, mainly from proteins of host cells, in both light and darkness. Continuous light delayed the main peak of both NH+4 production and K+ efflux. High CO2 concentration inhibited both processes, thus indicating that photorespiration plays a role in enhancing the release of free ammonium during bacterial pathogenesis. This is supported by shifts in the pattern of amino acids. The results demonstrate the accelerating and aggravating effect of ammonium in pathogenesis and HR, though ammonium is not the primary agent. [ABSTRACT FROM AUTHOR]

Endometriosis is considered primarily a disease of the endometrial-subendometrial unit or archimetra. The clinical picture of endometriosis characterises this disease as a hyperactivation of genuine archimetrial functions such as proliferation, inflammatory defence and peristalsis. While the aetiology of the disease remains to be elucidated, a key event appears to consist in the local production of extraovarian oestrogen by a pathological expression of the P450 aromatase. The starting event may consist in a hyperactivity of the endometrial inflammatory defence, a hyperactivity of the endometrial oxytocin/oxytocin receptor system or in the pathological expression of the P450 aromatase system itself. Regardless of which of these levels the starting event is localized in, they influence each other on both the level of the archimetra and the endometriotic lesions. Locally elevated oestrogen levels inevitably up-regulate the endometrial oxytocin mRNA and increased levels of oxytocin result in uterine hyper-peristalsis, increased transtubal seeding of endometrial tissue fragments and finally subfertility and infertility by impairment of the uterine mechanism of rapid and sustained sperm transport. Locally increased levels of oestrogen lead, on both the level of the endometrial-subendometrial unit and the endometriotic lesion, to processes of hyperproliferation. These processes result, on the level of the uterus, in an infiltrative growth of elements of the archimetra into the neometra and, on the level of the endometriotic lesion, in infiltrative endometriosis. There is circumstantial evidence that trauma might be an important initial event that induces the specific biochemical and cellular responses of the archimetra. This model is able to explain both the pleiomorphic appearance of endometriosis and the, up until now, enigmatic infertility associated with mild and moderate endometriosis. [ABSTRACT FROM PUBLISHER]

Uterine peristalsis, directing sustained and rapid sperm transport from the external cervical os or the cervical crypts to the isthmic part of the tube ipsilateral to the dominant follicle, changes in direction and frequency during the menstrual cycle, with lowest activity during menstruation and highest activity at mid cycle. It was therefore suggested that uterine peristalsis is under the control of the dominant follicle with the additional involvement of oxytocin. To test this hypothesis, vaginal sonography of uterine peristalsis was performed in the early, mid and late proliferative phases, respectively, of cycles of women treated with oestradiol valerate and with human menopausal gonadotrophin following pituitary downregulation, with clomiphene citrate and with intravenous oxytocin, respectively. Administration of oestradiol valerate resulted in oestradiol serum concentrations comparable with the normal cycle with a simulation of the normal frequency of peristaltic contractions. Elevated oestradiol concentrations and bolus injections of oxytocin resulted in a significant increase in the frequency of peristaltic contractions in the early and mid follicular phases, respectively. Chlomiphene tended, though insignificantly so, to suppress the frequency of peristaltic waves in the presence of elevated oestradiol concentrations. In the late follicular phase of the cycle extremely elevated oestradiol concentrations as well as the injection of oxytocin resulted only in an insignificant further increase of peristaltic frequency. In the normal cycles, as well as during extremely elevated oestradiol concentrations and following oxytocin administration, the peristaltic contractions were always confined to the subendometrial layer of the muscular wall. The results and the review of literature indicate that uterine peristalsis during the follicular phase of the menstrual cycle is controlled by oestradiol released from the dominant follicle with the probable involvement of oxytocin, which is presumably stimulated together with its receptor within the endometrial-subendometrial unit and therefore acting in an autocrine/paracrine fashion. Since unphysiological stimulation with oestradiol and oxytocin did not significantly increase the frequency of uterine peristalsis in the late follicular phase of the cycle it is assumed that normal preovulatory frequency of uterine peristalsis is at a level which cannot be significantly surpassed due to phenomena of refractoriness of the system. [ABSTRACT FROM AUTHOR]

Sperm transport from the cervix into the tube is an important uterine function within the process of reproduction. This function is exerted by uterine peristalsis and is controlled by the dominant ovarian structure via a cascade of endocrine events. The uterine peristaltic activity involves only the stratum subvasculare of the myometrium, which exhibits a predominantly circular arrangement of muscular fibres that separate at the fundal level into the fibres of the cornua and continue into the circular muscles of the respective tubes. Since spermatozoa are transported preferentially into the tube ipsilateral to the dominant follicle, this asymmetric uterine function may be controlled by the ovary via direct effects utilizing the utero-ovarian counter-current system, in addition to the systemic circulation. To test this possibility the sonographic characteristics of the uterine vascular bed were studied during different phases of the menstrual cycle. Vaginal sonography with the measurement of Doppler flow characteristics of both uterine arteries and of the arterial anastomoses of the uterine and ovarian arteries (junctional vessels) in the cornual region of both sides of the uterus during the menstrual phase of regular-cycling women demonstrated significant lower resistance indices of the junctional vessels ipsilateral to the side of the dominant ovarian structure as compared with the corresponding arteries contralaterally. By the use of the perfusion mode technique, it could be observed that vascular perfusion of the fundal myometrium was significantly increased ipsilateral to the dominant follicle during the late follicular phase of the cycle. These results show that the endocrine control of the dominant ovarian structure over uterine function is not only exerted via the systemic circulation but also directly, most probably utilizing the utero-ovarian counter-current system. [ABSTRACT FROM AUTHOR]

Women suffering from infertility in association with mostly mild endometriosis were subjected to vaginal sonography of uterine peristalsis during the menstrual period, the early, mid- and late follicular phases, and the mid-luteal phase of the menstrual cycle. The data obtained were compared with those of healthy controls. Women with endometriosis displayed a marked uterine hyperperistalsis that differed significantly from the peristalsis of the controls during the early and mid-follicular and mid-luteal phases. During the late follicular phase of the cycle, uterine peristalsis in women with endometriosis became dysperistaltic, arrhythmic and convulsive in character, while in controls peristalsis continued to show long and regular cervico-fundal contractions. Hysterosalpingoscintigraphy during the early, mid- and late follicular phases revealed that hyperperistalsis in the early and mid-follicular phases of patients with endometriosis resulted in a dramatic increase in the transport of inert particles from the vaginal depot, through the uterus into the tubes and also into the peritoneal cavity. During the late follicular phase of the cycle, the dysperistalsis observed in women with endometriosis resulted in a dramatic reduction of uterine transport capacity in comparison with the healthy controls. We consider uterine hyperperistalsis to be the mechanical cause of endometriosis rather than retrograde menstruation. Dysperistalsis in the late follicular phase of patients with endometriosis may compromise rapid sperm transport. Uterine hyperperistalsis and dysperistalsis are considered to be responsible for both reduced fertility and the development of endometriosis. [ABSTRACT FROM AUTHOR]