BSACI guidelines for the management of rhinosinusitis and nasal polyposis.

This guidance for the management of patients with rhinosinusitis and nasal polyposis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The recommendations are based on evidence and expert opinion and are evidence graded. These guidelines are for the benefit of both adult physicians and paediatricians treating allergic conditions. Rhinosinusitis implies inflammation of the nose and sinuses which may or may not have an infective component and includes nasal polyposis. Acute rhinosinusitis lasts up to 12 weeks and resolves completely. Chronic rhinosinusitis persists over 12 weeks and may involve acute exacerbations. Rhinosinusitis is common, affecting around 15% of the population and causes significant reduction in quality of life. The diagnosis is based largely on symptoms with confirmation by nasendoscopy. Computerized tomography scans and magnetic resonance imaging are abnormal in approximately one third of the population so are not recommended for routine diagnosis but should be reserved for those with acute complications, diagnostic uncertainty or failed medical therapy. Underlying conditions such as immune deficiency, Wegener's granulomatosis, Churg-Strauss syndrome, aspirin hypersensitivity and allergic fungal sinusitis may present as rhinosinusitis. There are few good quality trials in this area but the available evidence suggests that treatment is primarily medical, involving douching, corticosteroids, antibiotics, anti-leukotrienes, and anti-histamines. Endoscopic sinus surgery should be considered for complications, anatomical variations causing local obstruction, allergic fungal disease or patients who remain very symptomatic despite medical treatment. Further well conducted trials in clearly defined patient groups are needed to improve management.

A unified framework for constructing, tuning and assessing photometric redshift density estimates in a selection bias setting.

Photometric redshift estimation is an indispensable tool of precision cosmology. One problem that plagues the use of this tool in the era of large-scale sky surveys is that the bright galaxies that are selected for spectroscopic observation do not have properties that match those of (far more numerous) dimmer galaxies; thus, ill-designed empirical methods that produce accurate and precise redshift estimates for the former generally will not produce good estimates for the latter. In this paper, we provide a principled framework for generating conditional density estimates (i.e. photometric redshift PDFs) that takes into account selection bias and the covariate shift that this bias induces. We base our approach on the assumption that the probability that astronomers label a galaxy (i.e. determine its spectroscopic redshift) depends only on its measured (photometric and perhaps other) properties [Formula: see text] and not on its true redshift. With this assumption, we can explicitly write down risk functions that allow us to both tune and compare methods for estimating importance weights (i.e. the ratio of densities of unlabelled and labelled galaxies for different values of [Formula: see text]) and conditional densities. We also provide a method for combining multiple conditional density estimates for the same galaxy into a single estimate with better properties. We apply our risk functions to an analysis of ≈106 galaxies, mostly observed by Sloan Digital Sky Survey, and demonstrate through multiple diagnostic tests that our method achieves good conditional density estimates for the unlabelled galaxies.

Traditional risk factor assessment does not capture the extent of cardiovascular risk in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis. However, the degree of endothelial dysfunction and its relationship to traditional and novel cardiovascular risk factors have not been examined in SLE. METHODS: In a case-control design, 35 patients with clinically stable SLE and 35 control subjects matched for age, sex, body mass index and smoking status were studied. Arterial elasticity, lipid profile, homocysteine, measures of inflammation and oxidative stress were determined. RESULTS: Among traditional vascular risk factors, there was a nonsignificant trend towards lower blood pressure in the control subjects, whereas low-density lipoprotein (LDL) cholesterol levels were significantly lower in the SLE group (2.5 vs 3.3 mmol/L, P < 0.001). Patients with SLE had significantly lower small artery elasticity (SAE; 4.9 vs 7.0 ml/mmHg x 100, P < 0.001) and higher plasma homocysteine (11.4 vs 8.3 mmol/L, P = 0.002) than control subjects. Levels of serum sVCAM-1 (614 vs 494 ng/mL, P = 0.002), oxidized LDL (144 vs 97, P < 0.001) and CD40 ligand (4385 vs 1373 pg/ml, P = 0.001) were significantly higher in SLE. Oxidized LDL levels, older age at SLE diagnosis and higher disease damage scores correlated inversely with SAE but not traditional risk factors. CONCLUSION: Impaired endothelial function as shown by decreased SAE, and an adverse profile of novel proatherogenic and prothrombotic vascular disease risk factors were prevalent in clinically quiescent SLE. These findings show the vulnerability of patients with SLE for atherosclerosis, and emphasize that assessments based on traditional risk factors alone may be inadequate.

Characterization of a biotinylated somatostatin analog as a receptor probe.

The neuropeptide somatostatin (SRIF) triggers its biological effects by binding to high affinity membrane receptors. To develop a ligand useful for receptor affinity purification and localization, we have examined the ability of a novel monobiotinylated SRIF derivative to bind to receptors and streptavidin. Unlabeled [N-Biotinyl, Leu8, D-Trp22, Tyr25]SRIF28 (Bio-SRIF28) competed for [125I-Tyr11]SRIF binding to GH4C1 pituitary cell membranes with a Ki of 337 +/- 95 pM, comparable to that of native SRIF (193 +/- 16 pM). Studies using HPLC purified [125I]Bio-SRIF28 showed that equilibrium binding to membranes occurred within 120 min at 30 C and that the peptide-receptor complex dissociated slowly (t1/2 = 4.7 h). Analysis of saturation binding data gave an equilibrium dissociation constant for [125I]Bio-SRIF28 of 66 +/- 20 pM. Photoaffinity cross-linking of [125I]Bio-SRIF28 to membranes covalently labeled a broad 85 kDa band, as previously reported with the photolabile SRIF analog, [125I-Tyr11, Azidonitrobenzoyl-Lys4]SRIF. The binding of [125I]Bio-SRIF28 was potently inhibited by SRIF (Ki = 171 +/- 36 pM) and SRIF28 (299 +/- 102 pM) but not by structurally unrelated peptides. Furthermore, [125I]Bio-SRIF28 did not bind to membranes from GH(1)2C1 pituitary cells, which do not respond to SRIF and which lack [125I-Tyr11]SRIF binding sites. Finally, GppNHp and GTP gamma S both decreased [125I]Bio-SRIF28 binding whereas AppNHp did not. These studies showed that [125I]Bio-SRIF28 bound with high affinity to specific, G-protein coupled SRIF receptors. [125I]Bio-SRIF28 also bound with high affinity to streptavidin and this binding was very stable (t1/2 for dissociation = 19 h). Therefore, the affinity of the receptor for the Bio-SRIF28-streptavidin complex was determined by measuring the potency with which this preformed complex competed for [125I-Tyr11]SRIF binding. The Ki of the Bio-SRIF28-streptavidin complex (1110 +/- 47 pM) was only 3 times higher than that of uncomplexed Bio-SRIF28 (Ki = 337 +/- 95 pM). Dissociation of the [125I]Bio-SRIF28-streptavidin complex from receptors was slow (t1/2 = 3.9 h) but was increased over 200-fold by 1 microM GTP gamma S (t1/2 < 1 min). These data show that Bio-SRIF28 was able to bind simultaneously and with high affinity both to SRIF receptors and to streptavidin to form a stable ternary complex. Further, receptor binding of the Bio-SRIF28-streptavidin complex could be regulated by the addition of guanine nucleotides. Thus, Bio-SRIF28 should be useful for the affinity purification and in situ localization of SRIF receptors.

Monoclonal antibodies specific for rat relaxin. VI. Passive immunization with monoclonal antibodies throughout the second half of pregnancy disrupts histological changes associated with cervical softening at parturition in rats.

Relaxin, which is secreted by the corpora lutea throughout the second half of rat pregnancy, promotes the growth and softening of the cervix. The mechanisms at both the cellular and molecular levels by which relaxin brings about these effects remain to be determined. The present study examined the influence of endogenous relaxin on the histological changes associated with cervical softening. A monoclonal antibody for rat relaxin, designated MCA1, was injected iv daily on days 12-22 of gestation. Cervices were removed on day 22, fixed in 10% buffered formalin, embedded in paraffin, and processed for histological staining. Tissue sections (5 microns thick) were stained with Gomori's trichrome stain (collagen), Orcein stain (elastin), or periodic acid-Schiff (polysaccharide). Qualitative and quantitative analyses identified several histological parameters in MCA1-treated rats that differed markedly from those in control rats. Cervices obtained from MCA1-treated rats contained collagen fiber bundles with greater compactness; elastin fibers with greater density, length and interdigitation; arteries with smaller cross-sectional areas; and luminal involutions with smaller areas than controls. The cervices of MCA1-treated rats appeared to contain fewer vacuolated epithelial cells, which secrete polysaccharide-rich material, than did cervices obtained from controls. It seems plausible that most, if not all, of these relaxin-induced modifications of the histological characteristics of the cervix facilitate birth.

Evidence for a dual source of relaxin in the pregnant rat: immunolocalization in the corpora lutea and endometrium.

Uterine tissue was collected from intact pregnant rats on days 4, 10-15, 18, and 22 of pregnancy and day 2 postpartum and from rats on day 22 of pregnancy after ovariectomy (day 9) and progesterone-estrogen treatment. Placental, cervical, mammary, and pituitary tissues were collected from intact pregnant rats on day 22. Ovarian tissue was collected from intact pregnant rats on days 15, 20, and 22. These tissues were evaluated for relaxin immunostaining at the light microscope level using an antiserum to purified rat relaxin and the avidin biotin immunostaining technique. Since the corpus luteum is the major source of relaxin in the rat, this tissue was used as a positive control. Relaxin immunostaining in the corpus luteum was observed in a discrete region of the cytoplasm. This pattern of staining corresponded with the discrete clustering of relaxin-containing secretory granules found in the rat luteal cells. Relaxin was not observed in the day 22 placenta, cervix, mammary gland, pituitary gland, or day 4-13 pregnant uterus. Relaxin immunostaining was detected in endometrial epithelial cells on days 14-22 of pregnancy and day 2 postpartum. Relaxin immunostaining was more evident at implantation sites than between implantation sites. Antimesometrial epithelial cells at implantation sites contained relaxin immunostaining. The mesometrial surface, which consists of the placenta and decidualized endometrium, did not contain relaxin immunostaining. Relaxin immunostaining was also present in the endometrial epithelial cells of the day 22 pregnant rats that had been ovariectomized on day 9 and given subsequent replacement therapy with ovarian steroids. The presence of relaxin immunostaining in the ovariectomized rat indicates the endometrium is not sequestering relaxin secreted from the corpus luteum. These data provide evidence that the pregnant rat endometrium is a source of relaxin in addition to the corpus luteum. The appearance of relaxin in endometrial epithelial cells after implantation and its prominence at implantation sites may indicate that locally secreted conceptus factors stimulate endometrial relaxin synthesis.

Monoclonal antibodies specific for rat relaxin. V. Passive immunization with monoclonal antibodies throughout the second half of pregnancy disrupts development of the mammary apparatus and, hence, lactational performance in rats.

There were two related objectives to this study. The first was to determine the influence of relaxin on development of the mammary apparatus (nipples and glands) during the second half of pregnancy. The second was to determine whether the relaxin-dependent development of the mammary apparatus was required for normal postpartum lactational performance. Both objectives were accomplished by neutralizing endogenous relaxin throughout the second half of pregnancy with a monoclonal antibody specific for rat relaxin (MCA1). MCA1 was administered iv to rats daily from days 12-22 of pregnancy. On day 22 the morphology of the mammary apparatus of MCA1-treated rats differed from that of controls; nipples were dramatically smaller, collagen fibers had significantly greater mean density and consistency, and elastin fibers had greater mean density, length, and interdigitation. In addition, the mean number of alveoli surrounding lactiferous ducts was significantly smaller in MCA1-treated rats than in controls. There were no differences between MCA1-treated rats and controls in the mean thickness of connective tissue surrounding ducts, the height or density of luminal cells lining lactiferous ducts, or the sizes of either adipocytes or arteries. To examine lactational performance, MCA1-treated and control rats were cesarean sectioned between 2100-2400 h on day 22 of pregnancy and given foster pups born of untreated intact donors. Although both MCA1-treated rats and control rats exhibited a high incidence of maternal behavior after cesarean delivery, mean pup weight and incidence of live pups declined markedly during days 1-5 of fosterage in MCA1-treated rats compared to controls. Furthermore, unlike controls, there was no observable postpartum nipple development in MCA1-treated rats by day 5 of fosterage. Mammary glands obtained from MCA1-treated rats on day 5 of fosterage had markedly lower mean weight than controls. This study demonstrates that passive immunization of endogenous relaxin throughout the second half of pregnancy disrupts development of the nipples and mammary glands in the rat. Moreover, it establishes that relaxin's effects on the development of the mammary apparatus during pregnancy are essential for growth and survival of the young during lactation.

Influence of length of aortic occlusion with cold potassium cardioplegia on early and late mortality in cardiac valve replacement.

This study determines if prolonged aortic crossclamp time (ACC) with the use of cold potassium cardioplegia during elective cardiac valve replacement contributed to the risk of operative mortality in 225 patients. In Group I (143 patients), the ACC was less than 120 minutes (mean 86) and in Group II (82 patients), it was greater than 120 minutes (mean 146). The preoperative variables showed that Group II contained more severely ill patients who were undergoing more complex operations than in Group I. The operative mortality rate was 7% in Group I and 10% in Group II (p = not significant). Postoperative inotropic support was required in 13% of Group I and 30% of Group II patients (p less than 0.005). Operative mortality in patients in New York Heart Association (NYHA) functional class I and II was 0 and in patients in classes III and IV it was 13% (p less than 0.00008). Five percent of patients in NYHA classes I and II and 32% in classes III and IV required inotropic support (p less than 0.000005). The actuarial survival at 60 months was 88 +/- 3% for Group I and 77 +/- 7% for Group II (NS). For the NYHA class I and II patients, however, it was significantly better (98 +/- 2%) than class III and IV patients (75 +/- 5%) (p less than 0.0001). Analysis by logistic equation revealed that the NYHA functional classes III and IV were significant incremental risk factors for probability of in-hospital mortality (p less than 0.0001) but not the ACC time (p greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular laceration due to stented prosthesis.

Complications following open chest massage in patients with porcine xenografts in the mitral location have not been previously described. The authors report a case of cardiac resuscitation following mitral valve replacement with a stented porcine valve. The patient died following brief closed chest, and then, prolonged open chest, cardiac massage. Autopsy showed laceration of the left ventricle by the prosthetic valve stents. Physicians involved in the postoperative care of patients with stented prosthetic valves should be aware of this complication and should exercise caution when applying manual compression in the region of the posterolateral base of the heart.

Total excision of the sternum and thoracic pedicle transposition of the greater omentum; useful strategems in managing severe mediastinal infection following open heart surgery.

Mediastinal sepsis following open heart surgery is a significant cause of death. Open drainage of the mediastinumalone was employed originally in management of this problem. More recently, debridement, drainage, and reclosure have been used. Various irrigation solutions, such as antibiotics and Betadine, have been advocated to control severe mediastinal sepsis. Three principles of management in patients unresponsiveness to the above techniques have proved successful in two patients with life-threatening mediastinal sepsis: (1) radical, complete excision of the sternum and adjacent costal cartilages; (2) transposition of the greater omentum on a vascular pedicle to the mediastinum; and (3) primary closure with full-thickness rotational skin flaps. The radical excision of the sternum removes residual foci of sepsis in cartilage and sternal bone marrow. The transposition of the omentum provides a highly vascular, rapidly granulating covering for the contaminated great vessels and hase been successfully to prevent recurrence of suture line bleeding of an exposed ascending aortic anastomosis site. Primary closure of the wound with full-thickness skin flaps provides a suprisingly satisfactory covering for the heart. Preoperative and postoperative measurements of ventilatory mechanics have shown relatively small ventilatory impairment after the alteration of the thoracic cage imposed by excision of the sternum. Two patients have returned to active lives. A treatment failure probably due to incomplete adherence to these guidelines also is presented.

Free internal mammary artery graft. An improved surgical technique.

An improved method of free internal mammary artery (IMA)-to-ascending aorta anastomosis for cornoary bypass is described. We interposed a small patch of vein with a suitable side-branch or brancyes in connecting the proximal end of a detached IMA or radial artery. Thirty-four free IMA-to-coronary artery bypasses were performed in 25 patients; 16 right IMA, 14 left IMA, and 4 radial arteries were used. Cornoary angiographic follow-up studies performed in all patients between two weeks and six months after operation proved that all grafts were patent and showing a larger lumen than is usually seen in undetached IMA grafts. Concomitantly marked relief of anginal pain was noted in all patients. Oour experience with this technique is very encouraging. All patients are being followed to evaluate long-term graft patency.

Decompression of the heart with siphon drainage.

A simple technique for inducing intracavitary hypothermic cardioplegia and decompressing the left heart through the ascending aorta is presented. The technique is based on siphon drainage, which eliminates the dangers of air embolism.

Cold blood--potassium cardioplegia.

A technique is described for providing myocardial protection utilizing oxygenated blood that is drawn from the pump oxygenator and passed through two disposable cardioplegic cooling coils, which are joined in series and submerged in ice slush. A potassium-containing cardioplegic solution is run into the oxygenated blood at the level of the cooling coils. The amount of blood used in the blood-potassium cardioplegic mixture is controlled using a screw clamp. This method has been used with excellent results in 150 consecutive patients undergoing aortocoronary saphenous vein bypass grafting.

Selective intracavitary and coronary profound hypothermic cardioplegia for myocardial preservation: a new technique.

A technique is described for selective intracavitary and coronary hypothermic perfusion during cardiac bypass with cardioplegia to facilitate cardiac operations. A cold perfusate (Plasmalyte 148 and mannitol, 12.5 gm/L at 8 degrees to 10 degrees C) is administered with the aid of a low-flow perfusion pump into the left ventricular cavity and coronary circulation through an apical perfusion-venting (Per-Vent) catheter. This perfusate cools the myocardium rapidly and homogeneously to a temperature of 15 degrees to 20 degrees C. Within this temperature range, complete cardioplegia occurs and the safe ischemia period can be extended to 120 minutes. This method was applied in 50 unselected consecutive adult patients undergoing aortocoronary saphenous vein bypass grafting or aortic or mitral valve replacement. All patients survived and had excellent recovery of ventricular function.

Early and long-term effects on direct myocardial revascularization on cardiac function: a prospective study using multivariable physiological analysis.

Perioperative and late follow-up hemodynamic cardiovascular studies to assess the effects of direct myocardial revascularization on cardiac function objectively have been completed on 51 patients. Analysis of the data delineated three distinct groups basedon the patterns of their early postoperative recovery. Group I patients (12) had a hyperdynamic cardiovascular response to operation and returned to a normal physiological range of cardiac function within 24 hours. Group II patients (24) initially had moderate to severe myocardial decompensation postoperatively but responded to inotropic support and moved into the normal physiological range within 24 to 48 hours. Group III patients (15) had severe, prolonged myocardial decompensation with little response to inotropic support. There were no early deaths in Group I, 1 early iatrogenic death in Group II, and 2 deaths from sepsis, 1 in Group I and 1 in Group II. All 7 cardiogenic deaths occurred in Group III patients. Late follow-up studies 4 to 23 months postoperatively have been completed on 29 patients. These showed cardiovascular stability in the mean values in Groups I and II. Significant improvement in mean cardiac function was seen in surviving Group III patients.

Improved cardiovascular hemodynamics with atrioventricular sequential pacing compared with ventricular demand pacing.

To determine the advantages of atrioventricular (AV) sequential pacing over ventricular demand pacing, paired cardiovascular hemodynamic studies were performed in each pacing mode at a constant heart rate. The paired studies included determination of ejection fraction (EF) by echocardiography and gated blood pool radionuclide scanning, and of cardiac output (CO) by the indicator-dilution method. There was no significant difference in EF with either pacing mode. Determined by echocardiography, EF with AV sequential pacing was 57% compared with 56% with ventricular demand pacing; by the gated blood pool method, EF with AV sequential pacing was 58% compared with 57% in the ventricular mode. Significant improvement with AV sequential pacing was seen in CO (4.75 L/min from 3.75 L/min; p less than 0.01); stroke volume (58 ml from 48 ml; p less than 0.02); arteriovenous oxygen content difference (4.9 vol% from 5.6 vol%; p less than 0.01); total peripheral resistance (1,724 dynes sec cm-5 from 2,025 dynes sec cm-5; p less than 0.01); and cardiac contractility, as reflected by mixing time (6.9 seconds from 8.0 seconds; p less than 0.02). No significant changes were noted in mean arterial or atrial pressure or in systemic oxygen consumption. In a second group of 6 patients, similar paired studies were done in AV sequential pacing modes before and after therapeutic reduction of total peripheral resistance. A significant increase in CO (43%) was observed following reduction in total peripheral resistance. We conclude that AV sequential pacing improves CO more effectively than ventricular demand pacing. Cardiac output can be further enhanced in patients with congestive heart failure by pretreatment with agents to reduce total peripheral resistance.

Detection of creatine kinase BB isoenzyme in sera of patients undergoing aortocoronary bypass surgery.

Creatine kinase BB isoenzyme (CK-BB) was detected intraoperatively in 22 of 25 patients undergoing aortocoronary bypass surgery, both in the coronary sinus and in the mixed venous blood. In a group of 10 patients in whom selective intracavitary profound hypothermic arrest was used, CK-BB values were lower than in another group of 10 patients, in whom controlled ventricular fibrillation with moderate total body hypothermia was instituted. This latter group also had higher levels of CK-MB. Patients who developed acute myocardial infarction immediately prior to or during the surgical intervention had the highest CK-BB values. This enzyme appeared as early as 15 minutes after the institution of cardiopulmonary bypass and disappeared within 6 hours. It is considered that part of the BB isoenzyme in serum of patients undergoing heart surgery is of myocardial origin.

Medunsa and the training of black doctors for South Africa.

Medunsa, the Medical University of Southern Africa, was founded in 1976 to address both the under-representation of blacks in the health professions and the lack of good health care in the homelands. The university trains most of the black physicians, dentists, veterinarians, and allied health professionals in South Africa, and it places a great emphasis on community service and preventive medicine. Medunsa also has programs to help socially and academically disadvantaged applicants. In some respects, the ongoing development of Medunsa mirrors that of historically black health professions schools in the United States, and Medunsa struggles with some of the same problems. Medunsa can learn from the histories of these American schools as it faces the challenges of the post-apartheid era; in turn, all U.S. schools can learn from Medunsa's history as they struggle with physician supply questions and health care reform issues.

Hormonal bioassay of gonadotropin-producing hepatoblastoma.

Hepatoblastoma was associated with signs of isosexual precocity in an 11-month-old boy. Circulating gonadotropic hormone levels were elevated. Gonadotropic activity was demonstrated by bioassay in extracts of primary and metastatic tumor, and in media surrounding long-term tissue culture of the primary tumor. Morphology of the endocrine glands and bioassay of the pituitary gland obtained at autopsy indicated the presence of gonadotropins and other tropic hormones despite the physiologically abnormal hormone status. These ae the first direct studies of pituitary hormone content in this syndrome.