Computed tomography-guided transfacial buccal space core biopsy of deep head and neck space lesions: our experience.

Deep head and neck space lesions can present a number of diagnostic challenges due to their deep anatomical position and difficult access for diagnostic tissue sampling. We describe a series of percutaneous 'transfacial' buccal space computed tomography (CT)-guided core biopsies of these lesions and subsequent histological findings. Six patients underwent CT-guided core biopsy of deep parotid, parapharyngeal, or masticator space lesions over a 30-month period. We describe our biopsy technique and correlate our histological findings with subsequent surgical resection where performed. Five of six of CT-guided biopsies obtained sufficient tissue for histological interpretation with varying findings, including salivary gland tumours and squamous cell carcinoma confirmed on subsequent resection. One patient was treated palliatively following core biopsy. No biopsy-related complications were observed. In our small series, percutaneous CT-guided transfacial biopsy via the buccal space has proved an excellent option for the minimally invasive tissue acquisition of deep head and neck space lesions.

COVID-19 vaccination and low cervical lymphadenopathy in the two week neck lump clinic - a follow up audit.

The UK COVID vaccination programme has progressed at an astonishing rate since the first patients received their doses in December 2020. It is well known that other vaccines including influenza and human papilloma virus (HPV) can result in reactive lymphadenopathy in the axilla and/or neck. Patients are now presenting via the two week wait neck lump clinic with supraclavicular fossa and low neck lymphadenopathy related to COVID vaccination, and to similar one stop breast clinics with axillary lymph nodes. In an audit of 80 patients seen over a period of one month, we found COVID vaccine-related low neck lymphadenopathy in four cases (5%), with an additional rectal cancer patient thought to have metastatic disease who presented with a Virchow type node. COVID vaccine-related lymphadenopathy should be considered in the differential diagnosis of low-neck nodes if they occurred shortly after vaccination, but it is important to exclude sinister disease using ultrasound and other investigations as necessary.

Supraclavicular lymphadenopathy following COVID-19 vaccination: an increasing presentation to the two-week wait neck lump clinic?

The first COVID-19 vaccination was given in December 2020 and there is an effort to vaccinate the international population on a massive scale. Common side effects from the vaccine include headache and tiredness. Regional lymphadenopathy has been described in relation to other vaccines. We describe two cases of supraclavicular reactive lymphadenopathy presenting in patients who had the COVID vaccination in the ipsilateral arm. Awareness of this diagnosis is important for patients presenting to the neck lump clinic.

Early hepatic artery thrombosis after liver transplantation: a systematic review of the incidence, outcome and risk factors.

To clarify inconsistencies in the literature we performed a systematic review to identify the incidence, risk factors and outcome of early hepatic artery thrombosis (eHAT) after liver transplantation. We searched studies identified from databases (MEDLINE, EMBASE, Science Citation Index) and references of identified studies. Seventy-one studies out of 999 screened abstracts were eligible for this systematic review. The incidence of eHAT was 4.4% (843/21, 822); in children 8.3% and 2.9% in adults (p < 0.001). Doppler ultrasound screening (DUS) protocols varied from 'no routine' to 'three times a day.' The median time to detection was at day seven. The overall retransplantation rate was 53.1% and was higher in children (61.9%) than in adults (50%, p < 0.03). The overall mortality rate of patients with eHAT was 33.3% (range: 0-80%). Mortality in adults (34.3%) was higher than in children (25%, p < 0.03). The reported risk factors for eHAT were, cytomegalovirus mismatch (seropositive donor liver in seronegative recipient), retransplantation, arterial conduits, prolonged operation time, low recipient weight, variant arterial anatomy, and low volume transplantation centers. eHAT is associated with significant graft loss and mortality. Uniform definitions of eHAT and uniform treatment modalities are obligatory to confirm these results and to obtain a better understanding of this disastrous complication.

Cooking and drying as effective mechanisms in limiting the zoonotic effect of Mycobacterium bovis in beef.

For this study 48 non-infected muscle, lymphatic and visceral bovine tissue samples were collected from an approved red meat abattoir and spiked with 8 x 10(7) cfu/ml of M. bovis. The different spiked samples were subjected to cooking and drying (drying through the process of biltong-making) processes in a controlled laboratory environment. Mycobacterial isolates confirmed as M. bovis by means of polymerase chain reaction (PCR) were observed in 17 of a total of 576 samples that were exposed to the secondary processing method of cooking. The study showed that not only can M. bovis survive the cooking process but the survival of the bacterium will be determined by its unique adaptive changes to the surrounding composition of the environment. The results for the samples exposed to the drying process (n = 96) did not show any growth, suggesting that the process of biltong production as used in this study is likely to render infected meat safe for human consumption.

Chemical characterization of territorial marking fluid of male Bengal tiger, Panthera tigris.

The territorial marking fluid of the male Bengal tiger, Panthera tigris, consists of a mixture of urine and a small quantity of lipid material that may act as a controlled-release carrier for the volatile constituents of the fluid. Using gas chromatography and gas chromatography-mass spectrometry, 98 volatile compounds and elemental sulfur were identified in the marking fluid. Another 16 volatiles were tentatively identified. The majority of these compounds were alkanols, alkanals, 2-alkanones, branched and unbranched alkanoic acids, dimethyl esters of dicarboxylic acids, gamma- and delta-lactones, and compounds containing nitrogen or sulfur. Several samples of the marking fluid contained pure (R)-3-methyl-2-octanone, (R)-3-methyl-2-nonanone, and (R)-3-methyl-2-decanone, but these ketones were partly or completely racemized in other samples. The gamma-lactone (S)-(+)-(Z)-6-dodecen-4-olide and the C(8) to C(16) saturated (R)-gamma-lactones and (S)-delta-lactones were present in high enantiomeric purities. The chiral carboxylic acids, 2-methylnonanoic acid, 2-methyldecanoic acid, 2-methylundecanoic acid, and 2-ethylhexanoic acid were racemates. Cadaverine, putrescine, and 2-acetylpyrroline, previously reported as constituents of tiger urine, were not detected. The dominant contribution of some ketones, fatty acids, and lactones to the composition of the headspace of the marking fluid suggests that these compounds may be important constituents of the pheromone. Although it constitutes only a small proportion, the lipid fraction of the fluid contained larger quantities of the volatile organic compounds than the aqueous fraction (urine). The lipid derives its role as controlled-release carrier of the chemical message left by the tiger, from its affinity for the volatiles of the marking fluid. Six proteins with masses ranging from 16 to 69 kDa, inter alia, the carboxylesterase-like urinary protein known as cauxin, previously identified in the urine of the domestic cat and other felid species, were identified in the urine fraction of the marking fluid.

[The historical perspective of the sentinel lymph node concept]. / De geschiedenis van het schildwachtklierconcept.

The sentinel lymph node procedure is currently standard care in the treatment of breast cancer. The introduction of this procedure in 1992 would not have been possible without the pioneering discoveries regarding lymph nodes and cancer. The Italian surgeon Gaspar Asellius (1581-1626) visualized the lymphatic vessels of a dog after it had been fed and shortly before dissection. At the end of the 17th century, the French anatomists Lauth and Sappey visualized the lymphatics by injecting deceased criminals with mercury. In 1858, the German pathologist Virchow (1821-1902) launched the theory that lymph nodes act as defensive barriers. He also made the first microscopical illustration ofa sentinel lymph node. Gould et al. and Cabaãs independently launched the precursors of the current modern sentinel lymph node concept in 1959 and 1977 respectively. Gould et al. were the first people to use the term "sentinel node'. Cabañas used lymphangiography for the visualisation of the sentinel lymph node. Controversies about the barrier function of the lymph nodes, the fear of skip metastasis and the difficulties of performing the Cabañas procedure, prevented a breakthrough of this concept. In 1992 Morton et al. rediscovered the valuable sentinel node biopsy concept and introduced blue dye for the investigation of patients with melanoma. The combination of lymphoscintigraphy, intra-operative gamma probe guidance and patent blue further increased the reliability of the sentinel lymph node biopsy procedure. Unnecessary lymph gland dissection procedures with considerable morbidity can be prevented by this procedure.

[Clinical reasoning and decision making in practice. A 9-year-old boy with isolated splenomegaly]. / Klinisch denken en beslissen in de praktijk. Een 9-jarige jongen met een geïsoleerde splenomegalie.

Splenomegaly was discovered by chance in a 9-year-old boy who had no further complaints. Apart from splenomegaly and mild thrombocytopenia, no other pathological condition was found in the first instance. Ultrasound revealed a spleen with a median length of 16.7 cm. Blood tests remained stable and a bone marrow biopsy showed no pathology either. Doppler ultrasound of the splenic vessels was normal; screening for a coagulation disorder was not performed. A wait-and-see policy was instituted. Later, the patient developed haematemesis because ofoesophageal varices. It turned out that he had portal hypertension caused by thrombosis of the portal vein. The underlying cause was a heterozygous protein-C deficiency. Treatment consisted of anticoagulant therapy and a mesocaval shunt procedure. Splenomegaly is an atypical clinical manifestation in childhood. Coagulation disorders should be considered in children with splenomegaly.

[No 'connecting year' in the medical curriculum]. / Geen schakeljaar in de basisopleiding geneeskunde.

The step from house-man to residency is a large one. The medical curricula at the universities of Leiden and Utrecht have started a project called the 'schakeljaar' (connecting year). Such a connecting year is intended to make the transition smoother and may have the added advantage that one can start the postgraduate training more quickly. However, there are some critical remarks that can be made here. First of all, there does not seem to be such a major difference between the doctor that one becomes during the connecting year and the currently common optional houseman or eldest houseman. Secondly, it is questionable whether one can really start the postgraduate training more quickly. The capacity of the postgraduate training programmes is limited. Thirdly, relatively little time can be saved in the basic medical curriculum.

[A brief history of the inguinal hernia operation in adults]. / Een beknopte geschiedenis van de liesbreukoperatie bij volwassenen.

Late into the 19th century, treatment for inguinal hernias consisted of repositioning the hernia with trusses or using 'softening agents' such as warm herbal baths and moist bandages. Surgical resection or cauterisation, often combined with hemicastration, was only considered for cases ofstrangulated hernia that could not be repositioned. Bassini (1844-1924) is credited with developing the precursor to the modern inguinal hernia operation at the end of the 19th century. Bassini's essential discovery was that the transverse fascia plays a key role in the pathophysiology of inguinal hernias. Bassini's operation, consisting of complete incision of the transverse fascia and reconstruction of the inguinal floor, was considered the gold standard for nearly a century. One problem with the conventional Bassini operation was the tension applied to tissues, which led to a high rate of recurrence. Although Bassini's operation has now become obsolete, current surgical approaches still centre on fortification of the inguinal floor. This tension-free repair now uses synthetic mesh that is positioned using an open anterior approach, laparoscopic surgery, or a preperitoneal technique.

The influence of wire localisation for non-palpable breast lesions on visualisation of the sentinel node.

PURPOSE: In our clinic, patients with occult breast lesions are treated with a sentinel node biopsy combined with wire-guided tumour excision. The aim of this retrospective study was to determine the influence of the sequence of wire localisation and sentinel node procedure on visualisation of the sentinel node. METHODS: A total of 136 patients had a wire-guided tumour excision combined with a sentinel node procedure. Sixty-six patients had guide wire localisation prior to the sentinel node procedure. Seventy patients had sentinel node visualisation before insertion of the guide wire. RESULTS: The sentinel node was visualised in 41 (62%) of the patients who first underwent guide wire localisation. In the group of patients who underwent visualisation of the sentinel node before placement of the guide wire, the sentinel node was visualised in 62 (89%). This is a significant difference in visualisation (p<0.001). CONCLUSION: This study shows that guide wire localisation prior to the sentinel node procedure negatively influences visualisation of the sentinel node.

sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension.

Utilizing aortopulmonary vascular graft placement, we established a lamb model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. We previously demonstrated that endothelial nitric oxide synthase (eNOS) is increased in lambs at age 4 wk. However, these lambs display a selective impairment of endothelium-dependent pulmonary vasodilation that is suggestive of a derangement downstream of NO release. Thus our objective was to characterize potential alterations in the expression and activity of soluble guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5) induced by increased pulmonary blood flow and pulmonary hypertension. Late-gestational fetal lambs (n = 10) underwent in utero placement of an aortopulmonary vascular graft (shunt). Western blotting analysis on lung tissue from 4-wk-old shunted lambs and age-matched controls showed that protein for both subunits of sGC was increased in shunted lamb lungs compared with age-matched controls. Similarly, cGMP levels were increased in shunted lamb lungs compared with age-matched controls. However, PDE5 expression and activity were also increased in shunted lambs. Thus although cGMP generation was increased, concomitant upregulation of PDE5 expression and activity may have (at least partially) limited and accounted for the impairment of endothelium-dependent pulmonary vasodilation in shunted lambs.

Nicotine does not influence arterial lipid deposits in rabbits exposed to second-hand smoke.

BACKGROUND: Second-hand smoke (SHS) accelerates atherogenesis and impairs vascular function. The role of nicotine in this process has not been defined. METHODS AND RESULTS: To examine the potential effects of nicotine on atherogenesis and vascular function, 48 rabbits receiving a 0.5% cholesterol diet were randomized to control (cholesterol diet only), SHS from nicotine-standard research cigarettes (SHS-ST), and SHS from nicotine-free research cigarettes (SHS-NF). The SHS rabbits were exposed to 48 nicotine-standard (12 animals) or nicotine-free (12 animals) cigarettes/d, 5 d/wk for 10 weeks. Air carbon monoxide and particulates and plasma carboxyhemoglobin were significantly higher in the 2 SHS groups than the control group (P<0.001). The SHS-ST group had significant increases in plasma nicotine and cotinine compared with the other groups (P<0.001). There was no difference in serum lipids. Lipid lesions were increased in both SHS groups (54+/-5% [SEM] aorta and 66+/-4% pulmonary artery, 53+/-7% and 69+/-4%, and 39+/-4% and 43+/-3% in the SHS-ST, SHS-NF, and control groups, respectively; P=0.049 aorta and P<0.001 pulmonary artery). CONCLUSIONS: SHS exposure increased arterial lipid lesions, but nicotine did not contribute significantly to this effect. This effect is presumably due to other combustion products in the smoke.

Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy.

Our previous studies have demonstrated that inhaled nitric oxide (NO) decreases nitric oxide synthase (NOS) activity in vivo and that this inhibition is associated with rebound pulmonary hypertension upon acute withdrawal of inhaled NO. We have also demonstrated that inhaled NO elevates plasma endothelin-1 (ET-1) levels and that pretreatment with PD156707, an ETA receptor antagonist, blocks the rebound hypertension. The objectives of this study were to further elucidate the role of ET-1 in the rebound pulmonary hypertension upon acute withdrawal of inhaled NO. Inhaled NO (40 ppm) delivered to thirteen 4-week-old lambs decreased NOS activity by 36.2% in control lambs (P<0.05), whereas NOS activity was preserved in PD156707-treated lambs. When primary cultures of pulmonary artery smooth muscle cells were exposed to ET-1, superoxide production increased by 33% (P<0.05). This increase was blocked by a preincubation with PD156707. Furthermore, cotreatment of cells with ET-1 and NO increased peroxynitrite levels by 26% (P<0.05), whereas preincubation of purified human endothelial nitric oxide synthase (eNOS) protein with peroxynitrite generated a nitrated enzyme with 50% activity relative to control (P<0.05). Western blot analysis of peripheral lung extracts obtained after 24 hours of inhaled NO revealed a 90% reduction in 3-nitrotyrosine residues (P<0.05) in PD156707-treated lambs. The nitration of eNOS was also reduced by 40% in PD156707-treated lambs (P<0.05). These data suggest that the reduction of NOS activity associated with inhaled NO therapy may involve ETA receptor-mediated superoxide production. ETA receptor antagonists may prevent rebound pulmonary hypertension by protecting endogenous eNOS activity during inhaled NO therapy.

Shear stress regulation of endothelial NOS in fetal pulmonary arterial endothelial cells involves PKC.

We have shown that increased pulmonary blood flow at birth increases the activity and expression of endothelial nitric oxide (NO) synthase (eNOS). However, the signal transduction pathway regulating this process is unclear. Because protein kinase C (PKC) has been shown to be activated in response to shear stress, we undertook a study to examine its role in mediating shear stress effects on eNOS. Initial experiments demonstrated that PKC activity increased in response to shear stress. NO production in response to shear stress was found to be biphasic, with an increase in NO release up to 1 h, a plateau phase until 4 h, and another increase between 4 and 8 h. PKC inhibition reduced the initial rise in NO release by 50% and the second increase by 70%. eNOS mRNA and protein levels were also increased in response to shear stress, whereas PKC inhibition prevented this increase. The stimulation of PKC activity with phorbol ester increased eNOS gene expression without increasing NO release. These results suggest that PKC may play different roles in shear stress-mediated release of NO and increased eNOS gene expression.

Inhaled nitric oxide-induced rebound pulmonary hypertension: role for endothelin-1.

Clinically significant increases in pulmonary vascular resistance have been noted on acute withdrawal of inhaled nitric oxide (NO). Endothelin (ET)-1 is a vasoactive peptide produced by the vascular endothelium that may participate in the pathophysiology of pulmonary hypertension. The objectives of this study were to determine the effects of inhaled NO on endogenous ET-1 production in vivo in the intact lamb and to determine the potential role of ET-1 in the rebound pulmonary hypertension associated with the withdrawal of inhaled NO. Seven 1-mo-old vehicle-treated control lambs and six PD-156707 (an ET(A) receptor antagonist)-treated lambs were mechanically ventilated. Inhaled NO (40 parts per million) was administered for 24 h and then acutely withdrawn. After 24 h of inhaled NO, plasma ET-1 levels increased by 119.5 +/- 42.2% (P < 0.05). Western blot analysis revealed that protein levels of preproET-1, endothelin-converting enzyme-1alpha, and ET(A) and ET(B) receptors were unchanged. On acute withdrawal of NO, pulmonary vascular resistance (PVR) increased by 77.8% (P < 0.05) in control lambs but was unchanged (-5.5%) in PD-156707-treated lambs. Inhaled NO increased plasma ET-1 concentrations but not gene expression in the intact lamb, and ET(A) receptor blockade prevented the increase in PVR after NO withdrawal. These data suggest a role for ET-1 in the rebound pulmonary hypertension noted on acute withdrawal of inhaled NO.

Alterations in endogenous nitric oxide production after cardiopulmonary bypass in lambs with normal and increased pulmonary blood flow.

BACKGROUND: After cardiopulmonary bypass (CPB), altered vascular reactivity is a major source of complications, particularly for children with increased pulmonary blood flow. Although changes in agonist-induced NO activity are well described after CPB, potential changes in basal NO production and their role in post-CPB pulmonary hypertension remain unclear. By using aortopulmonary vascular graft placement in the fetal lamb (shunt lambs), we established a unique model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. The objective of the present study was to investigate potential alterations in endogenous NO production after CPB in lambs with normal and increased pulmonary blood flow. METHODS AND RESULTS: Vascular pressures and blood flows were monitored in 1-month-old lambs (n=7) with increased pulmonary blood flow and 6 age-matched control lambs. After shunt closure, hypothermic CPB (25 degrees C) was performed for 2 hours. The hemodynamic variables were monitored for 4 hours after CPB. Before, during, and after CPB, peripheral lung biopsies were performed to determine tissue NO, nitrite, nitrate, and cGMP concentrations; total NO synthase (NOS) activity; and endothelial NOS protein levels. Hypothermic CPB increased both mean pulmonary arterial pressure and left pulmonary vascular resistance (P:<0.05). The increase in pulmonary arterial pressure induced in shunt lambs was greater than that induced in control lambs (P:<0.05). Four hours after CPB, tissue concentrations of NO, nitrite, nitrate, and cGMP were decreased to approximately 70% of pre-CPB levels in both control and shunt lambs (P:<0.05). Total NOS activity and endothelial NOS protein levels were unchanged. CONCLUSIONS: Modest decreases in basal NO production, the inability to increase NO production, or both may play a role in the altered pulmonary vascular reactivity after CPB. The decrease in NO is independent of gene expression. However, other mechanisms for this decrease, such as substrate or cofactor availability, warrant further study.

Pulmonary blood flow alters nitric oxide production in patients undergoing device closure of atrial septal defects.

OBJECTIVE: To determine the effect of pulmonary blood flow (Qp) on nitric oxide (NO) production in patients with increased Qp due to an atrial septal defect (ASD). BACKGROUND: Alterations in pulmonary vascular NO production have been implicated in the development of pulmonary hypertension secondary to increased Qp. In vitro, acute changes in flow or shear stress alter NO production. However, the effect of Qp on lung NO production in vivo is unclear. METHODS: Nineteen patients (2.4-61 years of age, median 17) with secundum ASD undergoing device closure were studied. Before, and 30 min after ASD closure, exhaled NO and plasma nitrate concentration were measured by chemiluminescence (NOA 280, Sievers, Boulder, Colorado). RESULTS: Before ASD closure, all patients had increased Qp (Qp: systemic blood flow [Qs] of 2.0 +/- 0.7) and normal mean pulmonary arterial pressure (13.4 +/- 3.1 mm Hg). Atrial septal defect device closure decreased Qp from 6.0 +/- 2.5 to 3.6 +/- 1.3 L/min/m2 (p < 0.05). Mean pulmonary arterial pressure was unchanged. Associated with the decrease in Qp, both exhaled NO (-22.1%, p < 0.05) and plasma nitrate concentrations (-17.9%, p < 0.05) decreased. CONCLUSIONS: These data represent the first demonstration that acute changes in Qp alter pulmonary NO production in vivo in humans. Exhaled NO determinations may provide a noninvasive assessment of pulmonary vascular NO production in patients with congenital heart disease. Potential correlations between exhaled NO, pulmonary vascular reactivity and pulmonary hypertension warrant further study.

Altered regulation of the ET-1 cascade in lambs with increased pulmonary blood flow and pulmonary hypertension.

Plasma concentrations of endothelin-1 (ET-1) are increased in children with congenital heart disease associated with increased pulmonary blood flow. However, the role of ET-1 in the pathophysiology of pulmonary hypertension remains unclear. Preproendothelin-1 gene expression is increased in adults with advanced pulmonary hypertension. To characterize potential early molecular alterations in the ET-1 cascade induced by increased pulmonary blood flow and pulmonary hypertension, fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt). RNase protection assays and Western blot analysis were performed on lung tissue prepared from 4-wk-old shunt lambs and age-matched controls. Endothelin-converting enzyme-1 [the enzyme responsible for the production of active ET-1 from big ET-1, mRNA (411%, p<0.05)] and protein (170%, p<0.05) were increased in lung tissue prepared from shunt lambs, compared with age-matched controls. Endothelin type A receptor (the receptor that mediates vasoconstriction), mRNA (246%, p<0.05), and protein (176%, p<0.05) also were increased in lung tissue prepared from shunt lambs compared with age-matched controls. Conversely, endothelin type B receptor (the receptor that mediates vasodilation), mRNA (46%, p<0.05), and protein (65%, p<0.05) were decreased in shunt lambs. Both the mRNA and protein levels for preproendothelin-were unchanged. Thus we conclude that increased pulmonary blood flow and pulmonary hypertension induce early alterations in the ET-1 cascade that result in increased ET-1 production, increased ET-1-mediated vasoconstriction, and decreased vasodilation. These early alterations in gene expression may contribute to the development of pulmonary hypertension and its associated enhanced pulmonary vascular reactivity.

Inhaled nitric oxide inhibits NOS activity in lambs: potential mechanism for rebound pulmonary hypertension.

Life-threatening increases in pulmonary vascular resistance have been noted on acute withdrawal of inhaled nitric oxide (NO), although the mechanisms remain unknown. In vitro data suggest that exogenous NO exposure inhibits endothelial NO synthase (NOS) activity. Thus the objectives of this study were to determine the effects of inhaled NO therapy and its acute withdrawal on endogenous NOS activity and gene expression in vivo in the intact lamb. Six 1-mo-old lambs were mechanically ventilated and instrumented to measure vascular pressures and left pulmonary blood flow. Inhaled NO (40 ppm) acutely decreased left pulmonary vascular resistance by 27. 5 +/- 4.7% (P < 0.05). This was associated with a 207% increase in plasma cGMP concentrations (P < 0.05). After 6 h of inhaled NO, NOS activity was reduced to 44.3 +/- 5.9% of pre-NO values (P < 0.05). After acute withdrawal of NO, pulmonary vascular resistance increased by 52.1 +/- 11.6% (P < 0.05) and cGMP concentrations decreased. Both returned to pre-NO values within 60 min. One hour after NO withdrawal, NOS activity increased by 48.4 +/- 19.1% to 70% of pre-NO values (P < 0.05). Western blot analysis revealed that endothelial NOS protein levels remained unchanged throughout the study period. These data suggest a role for decreased endogenous NOS activity in the rebound pulmonary hypertension noted after acute withdrawal of inhaled NO.