Carcinogenic effect of chronic subcutaneous injections of 2,6-dimethylnitrosomorpholine in Sprague-Dawley rats

Sprague-Dawley rats received subcutaneous injections of 2,6-dimethylnitrosomorpholine (2,6-DMNM) at 3 different dose levels (1/5, 1/10 or 1/20 LD50) once weekly for life. Up to a 100% rate of tumors of the esophagus was detected in animals which received 1/10 and 1/20 LD50. In addition to tumors of this organ, neoplasms developed at different rates in the lungs and in the liver.     

Distraction intervention for preschoolers undergoing intramuscular injections and subcutaneous port access.

This study evaluated a distraction intervention designed to reduce the distress of preschool children undergoing repeated chemotherapy injections. Twenty-nine children aged 2-5 years were randomly assigned either to distraction by a developmentally appropriate electronic toy or to a wait-list control. Children who received the distraction intervention demonstrated lower overt behavioral distress and were rated by parents and nurses as less anxious than children in the control condition. The improvements were maintained over the 8-week intervention. The results suggest that a developmentally appropriate, multisensory, variable-distracting activity that requires active cognitive processing and active motor responses may be a viable cost-effective alternative to more time-intensive parent-training programs for preschool-age children. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Local nervous mechanism in regulation of blood flow in human subcutaneous tissue

The effect of local venous stasis upon blood flow in human subcutaneous adipose tissue on the distal part of the forearm was investigated in three healthy subjects and two chronically sympathectomized patients suffering from manual hyperhidrosis. The area under study was separated into two parts by means of a lead shield exerting a pressure of about 360 mmHg on the skin. The effect of venous stasis of about 40 mmHg on one side of the shield upon blood flow measured simultaneously on both sides of the shield by the local 133Xenon washout technique was investigated. During venous stasis on one side of the shield, blood flow decreased about 40% on both sides. The vasoconstrictor impulse could be transmitted over a distance of about 1-2 cm. The phenomenon was unaffected by nerve blockade induced 3 cm proximally, medially, and laterally to the area by infiltration the skin with lidocaine. Thus a vasoconstrictor impulse could be transmitted from the side of stasis to the non stasis side of the lead shield. The transmission was not affected by phentolamine but was blocked by lidocaine and chronic sympathetic denervation. The vasoconstrictor impulse elicited during venous stasis is therefore most likely transmitted by means of a local nervous mechanism involving sympathetic adrenergic vasoconstrictor fibres.     

Chronic intravenous injections of antigen induce and maintain tolerance in T cell receptor-transgenic mice

Antigen-specific T cell tolerance can be induced by systemic injection of high-dose antigen. In particular, a single intravenous (i.v.) injection of influenza virus hemagglutinin peptide in HNT-TCR transgenic mice induces T cell tolerance through thymocyte apoptosis as well as anergy and deletion of peripheral CD4+ T cells. We now show that this tolerance is reversed after 8 weeks probably due to the short in vivo half-life of the peptide. Since durable tolerance is required for this strategy to be of therapeutic value, we tested whether weekly i.v. injections of peptide (up to 12 weeks) could maintain the CD4+ T cell tolerance. Each injection induces a profound deletion of thymocytes, although their level recovers before the next injection. Therefore, during the treatment period, the thymus undergoes cycles of contraction/expansion. In the periphery, the number of CD4+ T cells is stably decreased and the persisting CD4+ T cells are hyporeactive both in vitro and in vivo. This tolerance is essentially peripheral since comparable results were obtained in thymectomized HNT-TCR mice injected weekly. Our data show that stable antigen-specific tolerance can be induced by repeated i.v. injections of antigen. These findings might have implications for the treatment of T cell-mediated autoimmune diseases.     

Local injections of corticotropin releasing factor reduce doxorubicin-induced acute inflammation in the eyelid

PURPOSE: Doxorubicin chemomyectomy is an effective alternative treatment option for patients with blepharospasm and hemifacial spasm. One side effect of the use of doxorubicin in localized injections is the development of acute inflammation and skin injury at the injection site. Corticotropin releasing factor (CRF) was reported to reduce inflammation after acute inflammatory injuries due to other causes and at other sites. This study was performed to assess the potential of CRF to prevent the development of skin injury and eyelid soreness after local doxorubicin injection. METHODS: Rabbits received lower eyelid injections of either 75 or 150 micrograms CRF followed by injection of either 0.5, 1, or 2 mg doxorubicin or doxorubicin alone. Eyelids were assessed for changes in acute inflammation by immunohistochemical localization of macrophages and monocytes using anti-CD11, an antibody specific for these cell types. Short-term alterations in vascular permeability were assessed using an Evans blue assay. Additional eyelids were followed daily for changes in the skin over the injection site to determine day of onset of skin injury and the total duration of skin injury. After 1 month, the eyelids were processed histologically for morphometric analysis of muscle fiber loss. Monkey eyelids also were examined for the effect of CRF and doxorubicin injections. RESULTS: Doxorubicin alone produced an acute inflammatory reaction in the treated eyelids, with a large influx of macrophages and monocytes throughout the connective tissue at 1 and 2 days. Corticotropin releasing factor pretreatment significantly reduced this influx of inflammatory cells into the connective tissue. Doxorubicin produced a large increase in vascular permeability in the treated eyelids, with resultant edema. Corticotropin releasing factor did not alter this change in vascular permeability, indicating that CRF appears to have a specific effect on migration of inflammatory cells rather than just a generalized effect on vascular permeability. Corticotropin releasing factor and doxorubicin cotreatments delayed the onset of skin injury and decreased the total duration of injury to the skin compared to doxorubicin alone. The effectiveness of doxorubicin chemomyectomy was maintained; muscle loss was significant at all doses of CRF combined with doxorubicin. CONCLUSIONS: Corticotropin releasing factor dramatically decreased the acute inflammatory reaction that results in the eyelid from local doxorubicin injections. Not only did CRF reduce the acute influx of monocytes and macrophages, but it protected the skin overlying the injection site, substantially reducing the extent of skin injury. The efficacy of doxorubicin-induced muscle toxicity was maintained. A treatment protocol that combines myotoxicity with antiinflammatory activity in the treated eyelids may lead to a more effective patient treatment by increasing patient acceptance. The potential should be explored that CRF may be of clinical use in limiting tissue injury when administered immediately after extravasation during cancer chemotherapy.     

Calcified subcutaneous nodules in patients with chronic renal failure as a result of injections with nadroparin (Fraxiparine)

We present a case of AL-type amyloidosis involving pulmonary parenchyma and hilar and mediastinal lymph nodes in a patient with Waldenstr?m's macroglobulinemia. Direct infiltration of pulmonary parenchyma by lymphocytes and plasma cells is an important factor in the etiology and pathogenesis of pulmonary manifestations of the disease. Despite detailed examination, we did not find amyloid depositions in any extrapulmonary site.     

Reversal of mucosal tolerance by subcutaneous administration of interleukin-12 at the site of attempted sensitization

The pharmacological properties of T-0509, (-)-(R)-1-(3,4-dihydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol, were compared with those of isoproterenol. In the radioligand binding studies of [125I]iodocyanopindolol with COS-7 cell membranes that transiently expressed beta-adrenoceptor subtypes, T-0509 exhibited 11- and 97-fold greater Ki values for beta 2- and beta 3-adrenoceptors, respectively, compared with beta 1-adrenoceptors. Affinities of beta 2- and beta 3-adrenoceptors to isoproterenol were 1.4- and 28-fold lower than that of beta 1-adrenoceptors, respectively. The maximal stimulatory effects of T-0509 on adenylyl cyclase of CHO-K1 (chinese hamster ovary K1) cell membranes expressing beta 1- or beta 2-adrenoceptors were 85% or 96% of those produced by isoproterenol, respectively. These results indicate that T-0509 is a relatively specific beta 1-adrenoceptor agonist with a high intrinsic activity as compared with isoproterenol.     

Activity and tolerance of a continuous subcutaneous infusion of interferon-alpha2b in patients with chronic hepatitis C

We administered interferon-alpha2b (IFN-alpha2b) by continuous subcutaneous infusion (60,000 IU/h, or 10 million IU/week) over 3 months to 7 patients with chronic hepatitis C. All had previously responded, as assessed by normalization of transaminases to the same dose of IFN administered by intermittent injection over 6 months, but had relapsed after cessation of therapy. The continuous infusion was tolerated well at the site of infusion, and the systemic side effects were similar in type but were lesser in intensity than with intermittent dosage. Four of 7 subjects had normalization of transaminase at the end of week 12 of therapy. Serum HCV RNA and HCV by PCR decreased with treatment, and there was a prompt and sustained increase in serum beta2-microglobulin and of 2', 5' OAS activity. The level of the latter appeared to correlate with response of the transaminase. Serum IFN concentrations were low but detectable throughout therapy. After stopping IFN administration, the transaminases in responders increased again to pretreatment levels.     

Local and systemic tolerance to orally administered dinitrochlorobenzene is not broken by cholera toxin

OBJECTIVE: Withdrawal of testosterone prevents the development of hyperglycaemia in male Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus (NIDDM), but the exact mechanism has not been established. The present studies were undertaken to examine a possible role of testosterone in the development of obesity in young OLETF rats who have not shown marked hyperphagia. METHODS: Body weight, food intake and circulating concentrations of metabolic factors including immunoreactive leptin (IRL) were measured at five weeks of age in young male OLETF rats and their lean controls, Long-Evans-Tokushima-Otsuka (LETO) rats. At six weeks of age, both LETO and OLETF rats were bilaterally orchiectomized (Orchx) and half of each group implanted with a silastic tube containing testosterone. After a three week observation period, all animals were killed and circulating concentrations of metabolic factors and the ob gene expression in retroperitoneal white adipose tissues were measured. RESULTS: Body weight and 24h food intake were already increased in OLETF rats at five weeks of age. Serum testosterone concentrations were significantly lower in OLETF rats than in LETO rats. Expression of the ob gene was significantly decreased in the retroperitoneal white adipose tissue of OLETF rats, and their serum IRL concentrations were lower. Food intake and body weight gain for three weeks after the operation were significantly lower in the Orchx group of OLETF rats than in the sham-operated group. Hyperglycaemia, accompanied by hyperinsulinaemia, was attenuated by orchiectomy in OLETF rats. Circulating IRL concentrations were significantly higher in OLETF rats than in LETO rats and decreased by orchiectomy. Testosterone supplement reversed all of the changes caused by orchiectomy in OLETF rats. In contrast, the changes, which were observed after orchiectomy in OLETF rats, were not obvious in LETO rats. CONCLUSION: The present data indicate that testosterone plays a role in the development of obesity and NIDDM in young OLETF rats, but that changes of leptin production in white adipose tissue may not be important in the development of obesity in young OLETF rats.     

Local and distant histopathological effects of unilateral amyloid-beta 25-35 injections into the amygdala of young F344 rats

To determine if amyloid-beta (A beta) induces tau-immunoreactivity (IR) and reactive astrocytosis in vivo, we injected A beta 25-35 (5.0 nmol) into the right amygdala of rats. At 8 days postinjection, the peptide induced tau-2 IR in neuronal cell bodies and processes ipsilaterally in the amygdala, cingulate cortex, and hippocampus. At 32 days postinjection, the intensity of tau-2 IR was greater than at 8 days in the amygdala and hippocampus, but not in the cingulate cortex. Induction of Alz-50 IR also was progressive but the morphology and distribution was different from tau-2 IR. Beaded fibers with occasional neuronal perikarya were visualized with Alz-50, and the IR was primarily observed in the ipsilateral amygdala. In addition, amygdaloid injections of A beta 25-35 induced reactive astrocytosis, particularly in the ipsilateral hippocampus at 32 days postoperatively. To our knowledge, this is the first study to show that in vivo injections of A beta 25-35 induce progressive transsynaptic cytoskeletal and astrogliotic reactions, that gradually spread from the area of injection to brain regions that have prominent efferent connections with that area. These findings also suggest a direct association between plaque and tangle formation in Alzheimer's disease.     

A case of subcutaneous cysticercosis

We report the fourth case of subcutaneous cysticercosis infected in Japan since 1975. The patient noticed a subcutaneous nodule on his left shoulder without symptoms for three years. No remarkable changes were found in laboratory findings and physical examination after surgical excision of the subcutaneous nodule. The adult worm of Taenia solium could not be found in the intestine. Histological findings revealed a cystic structure with a fibrous capsule and a protoscolex with suckers, hooks, and calcareous corpuscula. It was identified as a Cysticercus cellulosae hominis based on morphological characteristics. The patient has been living in the Kanto area of Japan and has never been outside Japan since he was born.     

A condemnation of subcutaneous fasciotomy

Controversy exists regarding the indications and methods for lower-extremity fasciotomy. Two recent cases at our institution in which recurrent, acute limb-threatening ischemia occurred despite adequate fascial division have convinced us that in certain situations subcutaneous fasciotomy is clearly inadequate. In both patients, both of whom were young, intact healthy skin between the lower extent of the incision and the malleolus acted as a tourniquet, causing recurrent compartment syndrome as reperfusion edema occurred after initial repair. We believe that therapeutic fasciotomy in young patients with relatively noncompliant skin should include division of skin from the knee to the ankle on at least one side to prevent a tourniquet effect by intact skin at the ankle.     

The regurgitation of large vitreous injections

The increasing prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV), particularly in Africa and Asia, led us to investigate the prevalence of HIV infection in immigrants with pulmonary TB at the time of arrival in the UK. We performed anonymous HIV testing of stored sera from 39/65 immigrants referred to our unit between January 1991 and December 1994, who had culture-positive pulmonary TB. None of the 39 patients tested was positive for either HIV-1 or HIV-2, and the characteristics of the 26 patients for whom no serum was available were similar to those of the tested group. Despite the need to consider concomitant HIV infection in any patient with TB, particularly those from an area of HIV endemnicity, the present data do not suggest that recently arrived refugees, asylum seekers, immigrants or long-term visitors to the UK constitute a group in whom dual infection of HIV and Mycobacterium tuberculosis is common.     

Susceptibility changes following bolus injections

The general mechanism of bulk magnetic susceptibility (BMS) induced MRI contrast following a bolus injection is elaborated. Combining radiolabeled tracer data for the first pass of a bolus injection through the human brain with the application of Wiedemann's law allows us to calculate the lower limit for the time course of the vascular BMS following the injection of any contrast agent. Superparamagnetic iron oxide particles produce a much larger effect than any mononuclear Ln(III) chelate. We also calculate the BMS changes occurring after a dilution bolus injection (of isosmolal physiological saline) subsequent to a prior slow infusion of an intravascular contrast agent. This technique bears some resemblance to the increasingly important approach that exploits changes in only the level of blood oxygenation. The calculation indicates that contrast changes after the dilution bolus injection are smaller than those following Ln(III) agent injections but larger than those due to changes in blood oxygenation and suggests a way to possibly enhance the latter. We present an in vivo study demonstrating the dilution bolus injection technique in the mouse brain, and that features its rapid repeatability. Extrapolation of these results to the human, however, indicates that the saline volumes required for venous injections, except possibly for cardiac studies, would be prohibitively large. Smaller, catheter-delivered arterial bolus injections are feasible. We also suggest a method for using an agent bolus injection to measure the parenchymal BMS, and thus the iron content, of pathologically iron-loaded tissue.