A "crush" course on rhabdomyolysis: risk stratification and clinical management update for the perioperative clinician.

Rhabdomyolysis, the release of myoglobin and other cellular breakdown products from necrotic muscle tissue, is seen in patients with crush injuries, drug overdose, malignant hyperthermia, muscular dystrophy, and with increasing frequency in obese patients undergoing routine procedures. For the perioperative clinician, managing the resultant shock, hyperkalemia, acidosis, and myoglobinuric acute kidney injury can present a significant challenge. Prompt recognition, hydration, and correction of metabolic disturbances may reduce or eliminate the need for long-term renal replacement therapy. This article reviews the pathophysiology and discusses key issues in the perioperative diagnosis, risk stratification, and management of rhabdomyolysis.

Atorvastatin reduces endotoxin-induced microvascular inflammation via NOSII.

In a lipopolysaccharide (LPS)-induced rat model of sepsis (endotoxaemia), we previously demonstrated that pravastatin reduced microvascular inflammation via increased endothelial nitric oxide synthase III (NOSIII). This study aimed to determine whether atorvastatin, the most commonly used statin for lowering cholesterol, exerted beneficial pleiotropic effects via a similar mechanism. The mesenteric microcirculation of anaesthetised male Wistar rats (308 ± 63 g, n = 54) was prepared for fluorescent intravital microscopy. Over 4 h, animals received intravenous (i.v.) administration of either saline, LPS (150 µg kg(-1) h(-1)) or LPS + atorvastatin (200 µg kg(-1) s.c., 18 and 3 h before LPS), with/without the non-specific NOS inhibitor L-NG-Nitroarginine Methyl Ester (L-NAME) (10 µg kg(-1) h(-1)) or NOSII-specific inhibitor 1400 W (20 µg kg(-1) min(-1)). LPS decreased mean arterial blood pressure (MAP) (4 h, control 113 ± 20 mmHg; LPS 70 ± 23 mmHg), being reversed by atorvastatin (105 ± 3 mmHg) (p < 0.05). LPS also increased macromolecular leak measured after 100 mg kg(-1) of i.v FITC-BSA (arbitrary grey level adjacent to venules), which again was attenuated by atorvastatin (control 1.9 ± 4.0; LPS 12.0 ± 2.4; LPS + atorvastatin 4.5 ± 2.2) (p < 0.05). Furthermore, immunohistochemistry identified that atorvastatin decreased LPS-induced upregulation of endothelial cell NOSII expression, but NOSIII was unchanged in all groups. Atorvastatin improved MAP and reduced microvascular inflammation during endotoxaemia, associated with a reduction of pro-inflammatory NOSII. This differs from previous studies, whereby pravastatin increased expression of NOSIII. Thus preoperative statins have beneficial anti-inflammatory effects during endotoxaemia, but careful consideration must be given to the specific statin being used.

Endocrine mucin-producing sweat gland carcinoma: report of two cases of an under-recognized malignant neoplasm and review of the literature.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade sweat gland carcinoma with a strong predilection to the eyelid region. It is histologically analogous to endocrine ductal carcinoma/solid papillary carcinoma of the breast and is characterized by a multinodular solid cystic mucinous tumor with immunoreactivity to neuroendocrine markers. Only 20 cases of this unusual tumor have been reported. We present the clinical and histopathologic findings of 2 new cases of EMPSGC and review the relevant literature. The histological differential diagnosis is discussed and attention drawn to the role of immunohistochemistry in clarifying the nosological position of EMPSGC within the spectrum of cutaneous mucinous neoplasms.

A review of combined orbital decompression and lower eyelid recession surgery for lower eyelid retraction in thyroid orbitopathy.

BACKGROUND/AIMS: Eyelid retraction in thyroid orbitopathy is traditionally managed with staged surgery after orbital decompression. We review the benefit of concurrent inferior retractor recession at the time of orbital decompression when closing a swinging-eyelid flap. METHODS: A retrospective, comparative, non-randomised clinical audit of 34 eyes of 22 patients with thyroid orbitopathy over a 3-year period was carried out. Patients were divided into a combined orbital decompression and inferior retractor recession (with lateral horn release) group (RG, n=13) and an orbital decompression non-recession group (NRG, n=21). Groups were matched for age, walls decompressed, volume of intraconal fat excised and improvement in exophthalmometry. Surgery involved one to three wall decompressions and intraconal fat excision via a swinging eyelid and transcaruncular approach. We report outcomes at 6 months based on postoperative standard photographs. Lower eyelid height, inferior scleral show and lower eyelid lateral flare were recorded by two blinded, independent assessors. RESULTS: The RG achieved a greater improvement in lower eyelid elevation (1.8 ± 0.8 mm) compared to the NRG (1.1 ± 0.8 mm) (p=0.042). The RG (58%) and NRG (40%) had improvement of lower lid lateral flare. Mean scleral show improved in both the RG (1.3 mm) and NRG (0.9 mm). No lower eyelid complications occurred. CONCLUSION: Combining orbital decompression with concurrent inferior retractor recession at the time of swinging-eyelid flap closure is safe and improves lower lid height postoperatively compared to decompression alone.

Early experience using a new modified bone nibbler for superior osteotomy during endonasal dacryocystorhinostomy.

PURPOSE: The authors report their experience of using a modified bone nibbler as an adjunct to achieving an adequate superior osteotomy for full lacrimal sac exposure during endoscopic dacryocystorhinostomy. METHODS: Prospective interventional case series of 19 procedures performed from September 2008 to May 2009. Nasal mucosal flaps were fashioned and osteotomy was started using a Kerrison punch. The modified bone nibbler was then used to complete superior osteotomy to allow full sac exposure beyond its fundus. Lacrimal sac marsupialization and flaps were completed. Primary success was defined as full sac exposure equivalent to that normally achieved using powered instrumentation (PI) in our unit. PI was used if adequate osteotomy had not been achieved. Secondary success was defined as anatomical patency and symptom relief based on fluorescein flow on nasoendoscopy and patency to lacrimal syringing. RESULTS: Nineteen endoscopic dacryocystorhinostomy procedures in 18 patients were carried out with the nibbler by, or under supervision of, the senior surgeon over an 8-month period. The mean patient age was 52 years (range, 26-78 years). The median follow up was 6 months (4-36 weeks). Septoplasty was required in 4 (21%) cases. In 16/19 (84.2%) cases, full sac exposure was achieved with the nibbler. Three patients required PI to complete the osteotomy. Symptomatic and anatomical success with a patent nasolacrimal system was achieved in all cases (100%). CONCLUSIONS: We report the use of a new modified bone nibbler for removal of superior bone, even as high as the nasal roof, which previously in our practice could be removed only with PI. It allows a large osteotomy comparable to that achieved with powered endoscopic dacryocystorhinostomy yet avoids the disposable costs of PI.

Assessing adrenal status in patients before and immediately after coronary artery bypass graft surgery.

OBJECTIVE: Patients with cortisol deficiency poorly tolerate any systemic inflammatory response syndrome (SIRS), and may die if not treated with sufficient exogenous glucocorticoids. Controversy surrounds what constitutes a 'normal' adrenal response in critical illness. This study uses conventional tests for adrenal insufficiency to investigate cortisol status in patients undergoing elective coronary artery bypass surgery, a condition frequently associated with SIRS. DESIGN: A prospective, observational study. METHODS: Thirty patients with impaired left ventricular function (ejection fraction >23% <50%) underwent basal ACTH measurement, and a short cosyntropin test (250 µg, i.v.) 1 week preoperatively, and at +4 h following induction of general anaesthesia. Preoperatively, a 30 min cortisol level post cosyntropin >550 nmol/l was taken as a normal response. RESULTS: Prior to surgery, all patients had a normal response to cosyntropin. Postoperatively, eight patients (26.7%) did not achieve stimulated cortisol levels >550 nmol/l and the mean peak cortisol postoperatively was lower (1048 vs 730 nmol/l; P<0.001). There was a significant rise in ACTH after surgery (21 vs 184 ng/l; P=0.007) and reduction in Δ-cortisol post cosyntropin (579 vs 229 nmol/l; P<0.001). There was no change in basal cortisol pre- and post-operatively (447 vs 501; P=0.4). All patients underwent routine, uneventful postoperative recovery. CONCLUSION: Up to one quarter of patients with a normal cortisol status preoperatively demonstrated a raised ACTH and deficient cortisol response postoperatively. Despite these responses, all patients had uneventful outcomes. These data reinforce the need for caution when interpreting results of endocrine testing following major surgery or in the intensive care environment, and that prognostic value of these results may be of limited use.

An endoscopic approach for the management of congenital lacrimal fistulae.

A 26-year-old male presented with left epiphora from a congenital lacrimal fistula. A dacryocystogram confirmed fistulous origin from the lacrimal sac, while syringing demonstrated coexisting partial nasolacrimal duct obstruction. Endoscopic dacryocystorhinostomy was performed with marsupialization of the lacrimal sac medial wall, facilitating direct visualization of the internal fistula origin on the lateral wall, and excision with a 3-mm punch biopsy trephine over a cannula guide. Postoperatively, his symptoms resolved with a minimal cutaneous scar. The authors present this modified surgical technique for fistula excision using an endoscopic dacryocystorhinostomy approach.

Orbitofacial rejuvenation of temple hollowing with Perlane injectable filler.

BACKGROUND: Temple hollowing with soft tissue volume loss is well recognized in HIV lipoatrophy. Similar changes occur as part of aging, with skeletalization of the orbital rim and clipping of the eyebrow tail. OBJECTIVES: The authors report their initial experience treating temple volume loss and orbitofacial asymmetry with nonanimal stabilized hyaluronic acid (NASHA). METHODS: This study was a retrospective, interventional case series with a patient satisfaction questionnaire and independent physician grading of results. Patients initially received approximately 1 mL of Perlane (Q-Med, Uppsala, Sweden; Medicis, Inc., Scottsdale, Arizona) injected into the superficial fascia of each temple. The filler was placed behind the frontozygomatic process to soften the bony contour of the lateral orbital rim. Outcome measures included satisfaction with injection procedure, fulfillment of expectations, satisfaction with appearance, change in self-confidence, the need for retreatment, and complications. RESULTS: Twenty patients were treated, for a total of 39 temples. Mean follow-up was nine months (range, four to 14 months). Patients were primarily female (90%), all were Caucasian, and their ages ranged from 20 to 60 years. Eighteen patients had age-related temple hollowing, one had dysthyroid volume loss, and one had hollowing due to orbitotemporal neurofibromatosis. The majority had 1-mL injections to each side (range, 0.3-3 mL). One patient received 3 mL to correct asymmetry. The procedure was well tolerated with ice pack cooling and no local anesthesia. Of 16 patients who replied to the questionnaire, 13 were very or moderately satisfied and requested repeat treatment, whereas three were only mildly satisfied or ambivalent. Side effects included transient mild or moderate discomfort, superficial vein prominence, and localized bruising. CONCLUSIONS: This series suggests the effective and safe application of Perlane in temple hollow rejuvenation and correction of asymmetry. It offers tolerability, high patient satisfaction, few complications, and the option of reversibility.

Constriction of rat extra-splenic veins to lipopolysaccharide involves endothelin-1.

The spleen has an important role in blood volume regulation and increased resistance of post-capillary hilar veins (in mesentery adjoining the spleen) can regulate this. This study investigated whether venular constriction to lipopolysaccharide (LPS) involved endothelin-1 (ET-1). Pressure myography was used to study isolated extra-splenic (hilar) vessels from male Wistar rats (n = 111). Arteries and veins were treated with LPS (50 microg ml(-1)) for 4 h. Extra-splenic veins constricted to LPS (p < 0.05), but there was no effect on arteries. Denudation did not abolish venular constriction to LPS, indicating an endothelial independent mechanism. However, the dual ET-1 receptor antagonist bosentan (10(-5) M) and specific ET(A) and ET(B) antagonists ABT-627 (atrasentan, 6.3 x 10(-6) M) and A-192621(1.45 x 10(-6) M) completely abolished constriction of LPS-treated veins. ET-1 alone also constricted the extra-splenic arteries and veins (p < 0.05), with a greater response observed in veins (p < 0.05). ELISA also confirmed that serum and spleen levels of ET-1 increased in response to LPS (p < 0.05). That LPS-induced constriction of extra-splenic veins is mediated by ET-1. Greater constriction of post- versus pre-capillary extra-splenic vessels to LPS would result in increased intra-splenic fluid extravasation and hypovolaemia in vivo.

Macromolecular leak from extrasplenic lymphatics during endotoxemia.

BACKGROUND: The spleen has an important physiological role in maintaining blood volume; this study aimed to determine whether during pathophysiological circumstances, namely endotoxemia, the extrasplenic pathway is dysfunctional. We hypothesize that increased 'leakiness' of lymphatics in response to lipopolysaccharide (LPS) provides a route for loss of protein-rich fluid into third spaces and prevents the spleen from maintaining blood volume homeostasis. METHODS AND RESULTS: Male Wistar rats (200-280 g, n = 24) were anesthetized with thiopental (40-90 mg x kg(-1) x hr(-1), i.v.) to study the extrasplenic (vessels in mesentery adjoining the spleen) and ileal mesenteric microcirculation using fluorescently labeled albumin (66 KDa FITC-BSA, 0.02 g.100 g(-1), i.v.) with intravital microscopy. LPS (150 microg x kg(-1) x hr(-1) i.v.) induced constriction of rat extrasplenic venules (-14 +/- 2.4% from 40.4 +/- 7.8 microm, p < 0.05) and no change in arteriolar diameter (-4.6 +/- 4.7% from 32.6 +/- 4.3 microm). As the spleen is freely permeable to protein, a greater increase in venular versus arteriolar extrasplenic resistance increases intrasplenic capillary hydrostatic pressure, leading to fluid efflux into the lymphatics, draining the spleen. In agreement we report here increased extrasplenic venular resistance with LPS and lymphatic dilation to accommodate this fluid (13.5 +/- 6% from 18.5 +/- 4.8 microm, p < 0.05). However, the extrasplenic pathway then appeared to dysfunction, with macromolecular leak from extrasplenic venules (24.6 +/- 6.4%, p < 0.05) and lymphatics (12.1 +/- 3.4%, p < 0.05), indicated by increased interstitial FITC-BSA fluorescence. This was less than from ileal mesenteric venules (324 +/- 32%, p < 0.05). There was a concurrent decrease in mean arterial pressure (T(180): -15.1 +/- 6.9% from MAP of 130.3 +/- 8.8 mmHg at T(0), p < 0.05). CONCLUSION: Lymphatics are generally considered to demonstrate unidirectional and inward uptake of large molecules. However, during endotoxemia, we have demonstrated that extrasplenic lymphatics also allow the leakage of large protein molecules out into interstitial spaces. Fluid losses from extrasplenic lymphatics could therefore contribute to hypovolemia and hypotension associated with sepsis.

Lipopolysaccharide alters vasodilation to atrial natriuretic peptide via nitric oxide and endothelin-1: time-dependent effects.

Nitric oxide (NO) induces vascular relaxation via cGMP in vascular smooth muscle (VSM) and is an important mediator of vascular tone during sepsis, as endothelial NO synthase (eNOS) may be upregulated during the early stages. Atrial natriuretic peptide (ANP) also stimulates cGMP via eNOS hence, this study aimed to investigate the role of NO in time-dependent altered vascular responses to ANP during the first 4h of exposure to bacterial lipopolysaccharide (LPS). We used male rat saphenous arteries [internal relaxed diameter 63-152 microm, n=48], mounted on a wire myograph and pre-constricted with phenylephrine. At 2h in the presence of LPS, there was increased relaxation to ANP in arteries exposed to LPS [16.3+/-2.4%, P<0.05]. However the response to ANP was not altered by the NOS inhibitor Nomega-nitro-l-arginine methyl ester (L-NAME, 10(-4)M) and following denudation (vessels without endothelium). At 4h there was no longer increased relaxation to ANP in the presence of LPS. Moreover the vasodilator response to ANP was significantly reduced following L-NAME or denudation [4.4+/-1.0% and 4.3+/-1.1% respectively, P<0.05]. However, the non-specific endothelin-1 (ET-1) receptor antagonist Bosentan [10(-5)M] increased dilatation in LPS exposed arteries at 1 and 2h, reaching significance at 4h [14.0+/-3.4%, P<0.05]. In summary, an endothelial and NO dependent mechanism is responsible for increased relaxation to ANP following 2h exposure to LPS. However after 4h an endothelial and NO independent process involving ET-1 is responsible for decreased relaxation to ANP. The enhanced response to ANP may exacerbate early systemic vasodilatation during early sepsis.

Variable angle of strabismus related to timing of opiate ingestion.

Heroin (diamorphine) is a highly addictive opiate with potential for misuse. A small number of reports have linked the commencement of heroin misuse to acute exotropia with diplopia and subsequent withdrawal to esotropia in individuals without previous symptoms.(1-5) We describe a young adult who sought strabismus surgery to correct a large-angle exotropia. Detailed patient history and orthoptic measurements at different times of the day revealed a fluctuating angle of divergence relating to the timing of opiate ingestion, rendering surgery inappropriate. We suggest that opiate misuse, which may not willingly be disclosed by patients, should be specifically asked about before acquired-strabismus surgery is undertaken in adults.

A hybrid hierarchical decision support system for cardiac surgical intensive care patients. Part II. Clinical implementation and evaluation.

OBJECTIVE: Patients emerging from cardiac surgery can display varying degrees of cardiovascular instability arising from potentially complex, multi-factorial and interlinked causes. Stabilization and control of the cardiovascular system are currently managed by healthcare experts using experiential knowledge, and, in some centers, manually inputted decision pathway algorithms. This paper describes a clinical trial undertaken to determine the basic functioning of a clinical decision support system (CDSS) designed and constructed by the authors to facilitate the control of the major cardiovascular components in the early post-operative phase. Part II follows Part I's description of the software and simulation testing of the CDSS, and describes the hardware setup of a patient monitoring and CDSS. The system is evaluated on three post-cardiac surgery intensive care patients whom had all undergone cardio-pulmonary bypass. METHODS: The study was approved by the Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust Research Ethics Committee and conducted at the North Trent cardio-thoracic surgical unit and cardiac intensive care unit (CICU), Northern General Hospital, Sheffield (UK). Patients considered as 'very likely' to require active intervention to support the cardiovascular function following routine cardiac surgery were recruited during pre-operative surgical and anesthetic assessment, giving written informed consent when admitted for their operation. These patients underwent routine induction and maintenance of anesthesia by a non-study consultant anesthetist and the operation performed. There were no restrictions placed on the types of invasive monitoring used, on the use of trans-oesophageal echocardiography, drug selection, or the anesthetic agents selected by the clinicians performing the operations. All patients had full, routine invasive and non-invasive monitoring applied, including electrocardiography, central venous and peripheral arterial catheterisation, urine outputs and central temperature. After chest closure the patients were transferred to the CICU, sedated and ventilated, and the study commenced by the study anesthetist (1st author). The patients were in a clinically stable condition when admitted to the unit, and were attended by the treating clinicians until the handover to the study anesthetist occurred. The LiDCOplus (lithium dilution cardiac output) monitor (LiDCO Limited, Flowers Building, Granta Park, Cambridge CB1 6GU, United Kingdom) was calibrated after attachment to the patient's arterial line, and the patient's beat-to-beat hemodynamic data transferred to the host laptop computer. The CDSS graphical interface displays the patient's clinical details and specific cardiovascular data and prompts the anesthetist to input the target ranges for each parameter, and select a suitable advisor frequency. This is the frequency with which the therapeutic advice is displayed on screen with an audible prompt for a control inputs from the anesthetist. In each case this was selected to be 30s. When the study anesthetist agreed with the CDSS advice (administration of fluid, commencing a drug, altering the drug infusion rate) the syringe motif on the "Advisor Infusion Rates" panel of the graphical interface was 'clicked' on and the infusion rate immediately and manually inputted to Graseby 3400 pumps. If any disagreement between the anesthetist and the computer's advice arose, the syringe motif on the "Expert Infusion Rates" panel of the preferred drug was 'clicked' on and the expert's therapeutic decision (e.g. infusion rate) was entered in the corresponding data field and then applied to the pump. During all trials, data was stored for off-line analysis. RESULTS: The CDSS successfully selected suitable drug therapies for each case and advised reasonable and appropriate infusion rates such that the study anesthetist did not have to override the suggested CDSS instructions and infusion rates. Under differing clinical conditions the system was able to maintain clinically appropriate and stable control of the cardiovascular system (CVS), with good profiles under noisy physiological measurements, and was readily able to regain control following transient deterioration of the patient hemodynamic parameters (coughing, or during blood sampling).

A hybrid hierarchical decision support system for cardiac surgical intensive care patients. Part I: Physiological modelling and decision support system design.

OBJECTIVE: To develop a clinical decision support system (CDSS) that models the different levels of the clinician's decision-making strategies when controlling post cardiac surgery patients weaned from cardio pulmonary bypass. METHODS: A clinical trial was conducted to define and elucidate an expert anesthetists' decision pathway utilised in controlling this patient population. This data and derived knowledge were used to elicit a decision-making model. The structural framework of the decision-making model is hierarchical, clearly defined, and dynamic. The decision levels are linked to five important components of the cardiovascular physiology in turn, i.e. the systolic blood pressure (SBP), central venous pressure (CVP), systemic vascular resistance (SVR), cardiac output (CO), and heart rate (HR). Progress down the hierarchy is dependent upon the normalisation of each physiological parameter to a value pre-selected by the clinician via fluid, chronotropes or inotropes. Since interventions at each and every level cause changes and disturbances in the other components, the proposed decision support model continuously refers back decision outcomes back to the SBP which is considered to be the overriding supervisory safety component in this hierarchical decision structure. The decision model was then translated into a computerised decision support system prototype and comprehensively tested on a physiological model of the human cardiovascular system. This model was able to reproduce conditions experienced by post-operative cardiac surgery patients including hypertension, hypovolemia, vasodilation and the systemic inflammatory response syndrome (SIRS). RESULTS: In all the simulated patients scenarios considered the CDSS was able to initiate similar therapeutic interventions to that of the expert, and as a result, was also able to control the hemodynamic parameters to the prescribed target values.

Reduced vascular response to phenylephrine during exposure to lipopolysaccharide in vitro involves nitric oxide and endothelin 1.

Nitric oxide (NO) and endothelin 1 (ET-1) increase significantly during the first 4 h of Escherichia coli lipopolysaccharide (LPS) exposure. The aim of this study was to investigate the role of these mediators in the reduced response to phenylephrine treatment. We used male rat saphenous arteries (internal relaxed diameter, 63-152 microm; n = 48), mounted on a wire myograph and subsequently treated with LPS. At 1 h, LPS (dose, 50 microg mL(-1)) significantly (P < 0.05) inhibited constriction to phenylephrine (concentration, 10(-1)M to 10(-6)M) (LPS concentration required for half maximal response [EC50], 10.82 +/- 1.08microM; Control EC50, 5.07 +/- 0.34microM). However, by removing the endothelium (denuded) or adding Nomega-nitro-L-arginine methyl ester (L-NAME; concentration, 10(-4) microM), the response to phenylephrine treatment was significantly improved compared with LPS only-treated arteries (LPS + denuded EC50, 7.04 +/- 1.12microM; LPS + L-NAME EC50, 2.64 +/- 0.63microM). On the other hand, denudation did not restore constriction to phenylephrine at 2 and 4 h. However, L-NAME and the nonspecific ET-1 receptor antagonist bosentan (concentration, 10(-5)M) improved constriction to phenylephrine in LPS-treated arteries (P < 0.05) at 4 h (LPS EC50, 998.50 +/- 447.10microM; LPS + L-NAME EC50, 65.23 +/- 25.61microM; LPS + bosentan EC50, 63.65 +/- 25.33microM). We conclude that endothelium-dependent mechanisms have an early role in the reduced responsiveness of vascular smooth muscle to vasoconstrictors during simulated septic conditions. Shortly after exposure to LPS (duration, 1 h), endothelium-derived NO seemed to have a role in reduced arterial constriction to phenylephrine, but later (4 h) ET-1 and endothelium-independent increase in NO seemed to contribute further to the loss of response.

LPS abolishes extrasplenic vasoconstriction to atrial natriuretic peptide: the role of NO and endothelin 1.

Sepsis causes changes in vascular resistance and hypovolemia. Previous studies have demonstrated that the spleen regulates blood volume via atrial natiuretic peptide (ANP). We hypothesized that LPS alters extrasplenic responses to ANP via endothelial-dependent mechanisms and studied the role of NO and endothelin 1 (ET-1). Isolated extrasplenic arteries and veins (vessels in mesentery adjoining spleen) were obtained from male Wistar rats weighing 200 to 280 g (n = 102) and mounted on a pressure myograph to determine intraluminal diameter for 4 h. Isolated vessels constricted in response to the half-maximum response of ANP (veins, 30% +/- 1.7%; arteries, 34.5 +/- 1.7%; P < 0.05), and this was abolished by the NO donor S-nitroso-N-acetylpenicillamine (SNAP 75 microM). Arteries and veins incubated with LPS (50 microg mL(-1) for 4 h) were unresponsive to ANP, and constriction was not restored by the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 100 microM). However, venular constriction returned in the presence of the ET-1 antagonist Bosentan, increasing from -1.5 +/- 1.2 (10 min) to -10 +/- 2.5% (4 h) with LPS + Bosentan (3 x 10(-6) M) compared with -2.3 +/- 1.2 and 0% with LPS alone. In conclusion, LPS abolished endothelial-dependent extrasplenic venular constriction to ANP partially due to increased ET-1, whereas NO seemed to modulate vascular responses to ANP.

Systemic remission of non-Hodgkin's lymphoma after intralesional interferon alpha-2b to bilateral conjunctival lymphomas.

PURPOSE: To report the beneficial systemic effect of a 5-week course of intralesional interferon alpha-2b (IFN-A) injections to bilateral conjunctival lymphomas in a patient with relapsing non-Hodgkin's lymphoma. DESIGN: Interventional case report. METHODS: A patient in relapse with non-Hodgkin's lymphoma who declined further systemic therapy received 1.5-million IU IFN-A injected intralesionally to each of two conjunctival lymphomas to reduce ocular discomfort. This dose was repeated 10 times over 5 weeks. RESULTS: Conjunctival, postauricular, and facial lesions clinically resolved within 3 months of the start of treatment. Inguinal lymph nodes reduced in size, and the patient reported increased well-being and less fatigue. Side effects included injection discomfort and mild flulike symptoms, which were well tolerated. The improvement lasted 6 months from the first IFN-A injection. CONCLUSIONS: Intralesional treatment of conjunctival lymphomas with IFN-A induced disappearance of the tumors and also had a beneficial systemic effect.