An immunohistochemical study of glucagonoma conducted on the metastatic lymph nodes from a patient with recurrent metastatic glucagonoma: Report of a case

In this report, we briefly present the case of a 67-year-old woman who developed recurrent glucagonoma with lymph node metastasis. An immunohistochemical study of the metastatic tumor revealed immunoreactivity of glucagon and protein kinase C (PKC)-, -, and - in the tumor cells, two types of which were seen by electron microscopy. One type had abundant secretory granules and mitochondria, while the other had few granules and mitochondria. Some granules were similar to typical A cell granules and others were atypical. An immunoelectron microscopic demonstration revealed PKC-, -, and - immunostaining in the cytoplasm of all the tumor cells, while some secretory granules had PKC immunostaining, and others had no immunostaining. Thus, it appears that metastatic glucagonoma and its associated granules are composed of two types of mature and immature cells or granules. As immunoreactivity of PKC- and - was found in the tumor cells, but not in the normal A cells of the islets of Langerhans, the PKC subspecies and , which are not present in normal pancreatic A cells, may exist in human glucagonoma cells.     

Antibodies directed at mouse IL-2-R α and β chains act in synergy to abolish T-cell proliferation in vitro and delayed type hypersensitivity reaction in vivo

The anti-mouse IL-2-R chain mAb TM-1 which, by itself, does not affect IL-2-dependent proliferation throught the high affinity mouse IL-2 receptor, was shown to cooperate in a synergistic way with a set of anti-IL-2-R chain mAbs both in vitro and in vivo. In vitro, when associated at equimolar concentrations, the TM-1/anti- mAb association was four to ten times more efficient at inhibiting the proliferation of the CTL-L2 cell line than was a similar concentration of anti- mAb alone. In addition, a bispecific antibody in which a Fab' fragment of TM-1 was covalently linked to a Fab' fragment of one of the anti- mAb (5A2) was shown to be as efficient as the TM-1/5A2 association. The association of TM-1 with 5A2 was also tested in vivo in a sheep red blood cell-induced delayed type hypersensitivity (DTH) model. TM-1 which, by itself, had no effect on DTH, induced a two- to threefold decrease in the doses of 5A2 required to suppress this cell-mediated immune reaction.     

Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate

We have quantified and characterized ₁-, ₂-and -adrenoceptor subtypes in porcine bladder detrusor and bladder neck, human bladder detrusor, and porcine and human prostate. ₁-, ₂- and -adrenoceptor were identified in radioligand binding studies using [³H]prazosin, [³H]RX 821002 and [¹²⁵I]iodocyanopindolol, respectively, as the radioligands. In porcine male and female detrusor and bladder neck and male prostate, adrenoceptors were detected in the order of abundance > _{2 1} (not detectable), with no major differences between the sexes or between detrusor and bladder neck. In human detrusor and prostate the order of abundance was > _{2 1} (not detectable) and ₁ > ₂. respectively. The ₂-adrenoceptors in all tissues were homogeneously of the _2A-subtype as evidenced by competition binding studies with yohimbine, prazosin, ARC 239 and oxymetazoline. The -adrenoceptors represented a mixed population with a dominance of the ₂-subtype in all tissues as demonstrated by competition binding with ICI 118,551 and CGP 20,712A. We conclude that pigs may be a suitable model for studies of detrusor function with respect to adrenoceptor expression. They may be less suitable for studies of bladder neck or prostate function.     

Computer assisted quantification of vasospasm on angiograms

Summary We describe a new computer-based, automated method for the assessment of in vivo cerebral vasospasm. Arterial diameter measurements were performed on post-processed digital substraction angiographic images, using pixel as the unit. Vasospasm which was difficult to detect by visual inspection could be measured by the stenosis quantification program. A computer-assisted method such as we describe might decrease the risk of subjective errors.     

A Systemic “dumb-bell” haemangiopericytoma

Summary Systemic haemangiopericytoma is a rare soft tissue tumour originating from pericytes which are contractile pericapillary cells, and represents less than one percent of all vascular neoplasms [5]. The most common site of involvement is the thigh followed by the retroperitoneum, while the paraspinal location is very rare [1, 3].We report the first case of systemic dumb-bell haemangiopericytoma illustrated radiologically, which mimick, a dorsal dumb-bell neurinoma.     

Primary bladder neck obstruction

Summary Primary bladder neck obstruction is not uncommon in young and middle age men. The symptoms are confounding and routine urologic investigation including cystometry, uroflow, voiding cystourethrography and cystourethroscopy often leads to an erroneous diagnosis of psychogenic voiding dysfunction, neurogenic bladder or prostatitis. An accurate diagnosis can be obtained by the simultaneous measurement of detrusor pressure and uroflow, preferably accompanied by radiographic visualization of the lower urinary tract during micturition. Treatment with bladder neck incision is usually curative, but often results in retrograde ejaculation.     

Spinous process-plasty following lumbar laminectomy as a contributing factor to spine stability

A 10-year retrospective study of 41 consecutive patients who underwent spinous process-plasty is presented. We carried out laminectomy of the lumbar spine in cases of spinal stenosis, dorsomedial herniated disc and recurrent disc herniation with firm scars (traumatic and tumour cases are not included). To forestall the development of laminectomy's negative effects on spine stability, we initiated the spinous processes' reconstruction. Two groups of patients who underwent laminectomy form the basis of this presentation, one group with spinous process-plasty (41 patients) and the other (11 patients) without it. On postoperative neutral and dynamic X-ray films we paid attention to horizontal displacements larger than 3 mm and to negative intervertebral angular displacement. Considering such criteria, only 3.8% of those with spinous process-plasty developed a radiographic instability in contrast to 25% of patients without spinous process-plasty. These results support the use of this technique, which provides postlaminectomy lumbar spine stability.     

Delayed discharge and acceptability of ambulatory surgery in adult outpatients receiving general anesthesia

Purpose Delay in discharge after ambulatory surgery impairs its cost-effectiveness. However, it is not self-evident that prolonged postoperative stay is associated with low quality of care and patient acceptability of ambulatory surgery. The aims of this study were to document factors affecting delay in discharge, recovery profiles, and patient acceptability in adult outpatients.Methods Perioperative data were collected prospectively on consecutive 726 adult same-day surgical patients receiving general anesthesia. Factors that affected home-readiness, discharge, and unanticipated admission were noted. Patients were followed up 24h after discharge using a standardized questionnaire to identify postdischarge symptoms, patients self-rated resumption of normal activity (RNA) level, and preference of outpatient procedure.Results Eighty-two percent of patients were discharged home <270min after operation, 16% were delayed (270min), and 2% required unanticipated admission. Delayed patients reported postdischarge pain more frequently (53%) and a lower 24-h postoperative RNA level (7.2 ± 1.8) and preference ratio (76%) than no-delay patients (34%, 8.0 ± 1.9, 87%, respectively; P < 0.001). Delay in home-readiness (165min) was mainly due to an adverse symptom, and delay in discharge after reaching home-readiness (150min) was mainly due to a persistent symptom (58%) or a social/system problem (34%). Causes of admission were perioperative complications (80%) or social reasons (20%).Conclusion Delays in discharge are mainly due to adverse symptoms or social/system problems. Delayed discharge is associated with increased postdischarge pain, lower RNA level, and patient acceptability. Appropriate care of postoperative symptoms and system management could prevent delay in discharge and improve patient RNA level and acceptability.This work was presented in part at the 7th Congress of the Japanese Society for Ambulatory Anesthesia at Nagoya, Japan     

Use of a pericardial fat pad flap for preventing bronchopleural fistula: An experimental study focusing on the angiogenesis and cytokine production of the fat pad

An experimental study was conducted to determine whether pericardial fat tissue could induce neovascularization and produce cytokines related to tissue repair. Neovascularization was examined using chick chorioallantoic membranes. Pieces of pericardial fat tissue, omentum, and intercostal muscle were individually placed on a number of chorioallantoic membranes and neovascularization induced by each material was assayed 6 days after the implantation. The intensity of neovascularization was in the order of pericardial fat omentum > muscle. Cytokines, such as interleukin 1 (IL-1) and , tumor necrosis factor- (TNF), interferon- (IFN-), and interleukin 6 (IL-6) were assayed in a culture supernatant of pericardial fat tissue. The latter was obtained 24h after the addition of lipopolysaccharide (LPS) following various incubation times. All cytokines other than IFN are known to play a part in tissue repair, whereas IFN is negatively related to tissue repair because it inhibits fibroblast growth. The pericardial fat tissue incubated with LPS produced a certain amount of IL-1 on day 1, and TNF on days 1 and 8, whereafter these values decreased to an undetectable level. Irrespective of the addition of LPS, a large amount of IL-6 was observed in the supernatant of pericardial fat tissue and it was detectable until day 29. On the contrary, INF was not detected at any assay time. These observations suggest that a pericardial fat pad flap could possibly be beneficial in the prevention of bronchopleural fistula after pulmonary resection.     

Lipid and protein histochemistry of enamel — Effects of fluoride

Summary Staining reactions for a number of histochemical procedures for lipophilic staining and protein were studied in the enamel matrix along the length of rat incisors. Sudan Black gave a positive stain across the whole thickness of very early enamel (up to 30 m) but this staining only continued as a narrow band close to the ameloblasts as the enamel matured. A variety of tests for protein produced almost identical staining patterns in enamel matrix up to 100 m thick. Since the pattern of lipid staining persisted, after using a number of procedures which could normally be expected to remove lipid, it is suggested that Sudan Black positive staining may be due to lipophilic protein rather than lipid itself. Fluoride did not significantly alter the staining reactions for lipid and protein but did proceduce matrix which was much more effectively stained by cross-linking agents FFDNB and FF sulphene.     

Percutaneous and Open Renal Revascularizations Have Equivalent Long-Term Functional Outcomes

Atherosclerotic renal artery stenosis is a significant cause of poorly controlled hypertension and progressive renal dysfunction leading to ischemic nephropathy and other end-organ damage. The optimal treatment of renovascular disease contributing to hypertension and renal dysfunction is not known. This study compares the anatomic and functional outcomes of both open and endovascular therapy for chronic, symptomatic atherosclerotic renal artery disease. We performed a retrospective analysis of records from patients who underwent renal arterial interventions, endovascular or open bypass, between January 1984 and January 2004. Principal indications for intervention were hypertension (51%), chronic renal insufficiency (13%), and hypertension and elevated creatinine (36%). A total of 247 patients (109 males; mean age 69±10, range 44–89 years) underwent 314 interventions (109 open procedures; 205 angioplasties, 71% with stent placement). There was a significant difference in 30-day mortality (4% vs. <1%; p < 0.005) between the open and endoluminal groups, but not at 1, 3, or 5 years. Patients in the open group had a higher primary patency rate at 5 years (83±5% vs. 76±6%; p=0.03), but patients in the endoluminal group had a higher assisted primary patency rate at 5 years (92±5% vs. 84±5; p=0.03). There was no significant difference between both treatment groups in cumulative freedom from presenting symptom or in freedom from dialysis and renal-related death. Patients who presented with hypertension were more likely to have shown improvement in their blood pressure with endoluminal intervention at 1, 3, and 5 (59±6% endoluminal vs. 83±5% open; p=0.01) years. From these results we conclude that open repair and endoluminal repair of atherosclerotic renal artery stenosis have similar immediate and long-term functional and anatomic outcomes. Patients who present with hypertension may have greater benefit with an endoluminal repair.Presented at the Twenty-ninth Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, 2004.     

Analysis of oxygen transport to the brain when two or more parameters are affected simultaneously

We composed a model, combining oxygen transport system from blood to tissue with the oxygen consumption system at the tissue. The aim of this study is to apply it to the brain tissue under conditions when two or more oxygen transport parameters are affected simultaneously. The following values were assumed. Critical tissue P_{O 2} (Pcrit_{O 2}) 2mmHg; oxygen consumption above this level 3ml·min^–1·100g^–1; diffusion coefficient from blood vessel to tissue (Dvt) 0.2ml·min^–1·mmHg^–1·100g^–1; cerebral bloow flow (CBF) 50ml·min^–1·100g^–1; hemoglobin 15g·100ml^–1. The Hill equation was used for oxygen dissociation curve with n of 2.7 and P₅₀ of 27.0mmHg.The changes of oxygen consumption of the brain (V¨_{O 2}) were analyzed when 2 or more of 5 parameters, Pa_{O 2}, CBF, Dvt, P₅₀ and hemoglobin decreased simultaneously from their respective normal values.As the number of parameters affected increased, the level at which oxygen consumption begins to be affected became higher. With all five parameters combined, a reduction down to 78 per cent of normal resulted in tissue hypoxia. We conclude that the oxygen consumption of the brain is fairly resistant when only one parameter is affected, but it becomes increasingly vulnerable when several parameters are affected simultaneously. A clinically important finding is that the brain is particularly vulnerable to a combination of hypocapnia and a decreased level of 2,3DPG.(Suwa K: Analysis of oxygen transport to the brain when two or more parameters are affected simultaneously. J Anesth 6: 297–304, 1992)     

“High spinal” dysrhaphism

Summary High spinal (cervical and upper thoracic) dysrhaphism usually involves either a meningocele or a dermal sinus tract. These high spinal lesions can have a complex intradural anatomy at the level of the lesion (as this case reports) and are associated with an increased incidence of lower spinal occult dysrhaphic anomalies. It is therefore recommended that patients with high spinal dysrhaphism undergo radiological evaluation of the entire spine to identify those patients with intradural anomalies, define the anatomy for surgery, and investigate the lower spine for associated occult anomalies.     

The Mammary Fat Pad

The mammary fat pad is essential for developmentof the mammary epithelium, providing signals thatmediate ductal morphogenesis and, probably, alveolardifferentiation. The cleared fat pad is often used as a transplantation site.Considering the crucial role of the fat pad, itsproperties have received relatively little attentionfrom researchers in the field. Some of the questionswhose investigation is pertinent to understanding both normalmammary development and carcinogenesis are outlined inthis commentary in the spirit of stimulating enquiryinto this important subject. It is clear from a brief perusal of the available literature that untilstudies are specifically designed to clearlydifferentiate between functional effects of the fibrousand the adipose stroma, more substantive informationabout their differential effects on mammarydevelopment and tumorigenesis will not beforthcoming.     

Demonstration of the 5-flap technique

Summary Demonstration of the 5-flap technique which is double opposed Z-plasty and Y – V advancement is presented. A 4×4 gauze serves to demonstrate this technique.The authors dedicate this paper to the dear memory of their teacher, the late Prof. Zvi Neuman, who passed away untimely on March 22, 1977     

The role of TGF-β in patterning and growth of the mammary ductal tree

Evidence that transforming growth factor beta (TGF-)⁴ influences pattern formation in the developing mammary gland and negatively regulates ductal growth is reviewed. In the mouse, overexpression of TGF- transgenes during puberty reduces the rate of growth of the ductal tree and simplifies the pattern of arborization, while expression during pregnancy also interferes with lactation. Expression studies in the normal mouse gland indicate that TGF- is synthesized in the mammary epithelium, with the three isoforms showing somewhat different spatial and temporal distributions. Exogenous TGF- applied directly to the glandin situ inhibits epithelial cell division within hours, and strongly stimulates extracellular matrix synthesis over a longer time course. Normal human breast cells as well as certain breast cancer cell lines also secrete TGF- and are themselves inhibited by it, suggesting an autoregulatory feedback circuit, that in some cases appears to be modulated by estradiol. Taken together, the evidence suggests a model in which growth and patterning of the mammary ductal tree are regulated, at least in part, by TGF- operating through an autocrine feedback mechanism and by paracrine circuits associated with epithelial-stromal interactions.     

Effects of lead on osteoclast-like cell formation in mouse bone marrow cell cultures

To examine an effect of lead (Pb) on the process of osteoclast-like cell formation from its progenitors, we used a mouse bone marrow culture system in which osteoclast-like multinucleated cells (MNCs) were formed in response to bone-resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC formation over the concentration range 2–10 M, whereas at 40 M Pb, MNC formation declined. In an 11-day culture period, MNC formation reached a maximum at 5 M Pb and decreased with increasing concentration of Pb at 10–40 M. Pb-stimulated MNC formation was inhibited by both indomethacin and SC19220, an antagonist of prostaglandin E₂ (PGE₂) receptor. Pb stimulated the production of PGE₂ in marrow cell cultures, suggesting that Pb-stimulated MNC formation is dependent on the production of PGE₂. 3-Isobutyl-1-methylxanthine potentiated Pb-stimulated MNC formation and 2,5-dideoxyadenosine, an inhibitor of adenylate cyclase, inhibited it. A calcium ionophore A23187 increased Pb-induced MNC formation and verapamil, a calcium channel blocker, depressed it. It is possible that a PGE₂-induced increase in the levels of cyclic adenosine 3,5-monophosphate (cAMP) and calcium ions in marrow cells is involved in Pb-induced MNC formation. Pb and parathyroid hormone showed a synergistic stimulation on MNC formation. From these results, Pb is thought to induce osteoclast-like cell formation by a mechanism involving PGE₂ which increases the intracellular levels of cAMP and calcium ions.     

The intrathecal spread of hyperbaric dibucaine in adolescents

We investigated the spread of spinal anesthesia with hyperbaric dibucaine in 20 adolescents aged 9–18yr and 20 adults aged 23–53yr. No significant difference was found between the two groups with regard to height, whereas a statistical significant was found between the two groups with regard to weight. Spinal anesthesia was conducted with Neo-Percamin S^® injected at the L3–L4 interspace through a 25-gauge spinal needle. Injected volumes of the anesthetic solution were calculated from the patients height at 0.01ml·cm^–1. In adolescents, 1.6 ± 0.1ml (mean ± SD) of the anesthetic solution produced 19.4 ± 1.5 spinal segments blocked. In adults, 1.6 ± 0.1ml of the solution produced 13.4 ± 1.6 spinal segments blocked. A high spinal anesthesia above T5 was achieved in 17 (85%) patients in adolescents, whereas such a high level of spinal anesthesia was not experienced in adults. These results suggest that the hyperbaric dibucaine solution for spinal anesthesia in adolescents may have a tendency to produce an unexpectedly extensive spread of anesthesia.(Hirabayashi Y, Shimizu R: The intrathecal spread of hyperbaric dibucaine in adolescents. J Anesth 7: 167–172, 1993)     

Differential expression of transforming growth factor-β1 and β3 as well as C-FOS mRNA in normal human prostate,benign prostatic hyperplasia and prostatic cancer

Summary The discrepancy between the incidence of latent prostate cancer and that of clinically overt carcinoma suggests that there can be different courses in the biological progression of prostate cancer. As this cancer is detected increasingly at an infraclinical stage, markers are needed to indicate which lesions will progress and lead to the patient's death. To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors 1 (TGF-1), TGF-2 and TGF-3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. Our data demonstrate that expression of TGF-1 increased, whereas that of TGF-3 fell to an almost undetectable level in carcinoma. Expression of c-fos followed the TGF-1 pattern, whereas no difference could be seen in c-jun expression in cancer as compared with BPH and normal prostate. The differential expression of TGF-1, TGF-3 and c-fos could possibly be used to improve the characterisation of prostate cancer. Long-term follow-up of patients may indicate whether mRNA levels of these growth factors and oncogenes correlate clinically and whether they can be used as markers for progression in human prostate cancer.     

Complex role of tumor cell transforming growth factor (TGF)-βs on breast carcinoma progression

Growth inhibition by the TGF-s has been extensively studied in both normal and transformed mammary epithelial cells. It has been proposed that loss of autocrine TGF- mediated growth regulation is a critical event in breast tumorigenesis and several lines ofin vitro andin vivo data support this hypothesis. However, a positive association between the expression of TGF-s by tumor cells and the progression or maintenance of breast cancinoma cells has been observed in many studies inin vivo tumor models. Possible mechanisms for these growth enhancing effects of TGF- include immunosuppression mediated by tumor TGF-s, enhanced angiogenesis, increased peritumoral stroma formation, and cell adhesion. The net effect of tumor cell TGF- on the biology of breast carcinogenesis would depend on the balance between autocrine growth inhibition of mammary epithelial cells and these growth enhancing effects.