Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN+ fibroblasts and SPP1+ macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8+ T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.

[Best evidence summary of prevention strategies for pressure injury in adult hospitalized burn patients].

Objective: To summarize the best evidence of prevention strategies for pressure injury in adult hospitalized burn patients. Methods: A bibliometric approach was used. Systematic searches were carried out to retrieve the published evidence of prevention strategies for pressure injury in adult hospitalized burn patients in the official websites of relevant academic organizations such as International Society for Burn injury, American Burn Association, and Japanese Dermatology Association, National Pressure Injury Advisory Panel, European Pressure Injury Advisory Panel, Pan Pacific Pressure Injury Alliance International Guidelines Website, foreign language databases such as UpToDate, BMJ Best Practice, MedSci, Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, Web of Science, Embase, and PubMed, and Chinese databases such as China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, and China Clinical Guidelines Library. The literature types include clinical decision-making, evidence summary, guidelines, systematic review, and expert consensus. The search time was till February 21st, 2023. Two researchers independently screened the literature and evaluated the quality, and other researchers extracted and graded the evidence according to the topic. Results: A total of 10 papers were included, including 6 evidence summaries, 3 guidelines, and 1 expert consensus, all with high literature quality. After extracting evidence and classifying, 27 pieces of best evidences were summarized from three aspects, including prevention training and supervision, risk assessment, and prevention measures of pressure injury. Conclusions: A total of 27 pieces of best evidences of prevention strategies for pressure injury in adult hospitalized burn patients were summarized from 3 aspects. Medical workers can follow the best evidence and give personalized prevention strategies according to the specific condition of adult hospitalized burn patients to reduce the incidence of pressure injury.

[Associations between different levels of blood pressure and risk of prediabetes].

Objective: To explore sex and rural-urban differences in the associations of different blood pressure levels with the risk of prediabetes. Methods: We used a multi-stage stratified cluster random sampling method to investigate 21 637 residents aged ≥18 years from 10 survey areas in Hubei province in 2020. The data on questionnaire, physical measurements, and laboratory indicators of the participants were collected. The associations of different blood pressure levels with risk of prediabetes by sex and regions were analyzed using multivariate logistic regressions after complex weighting. Results: A total of 16 111 subjects were included. The prevalence (95%CI) of prediabetes, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and IFG complicated with IGT were 25.1% (14.4%-35.9%), 12.7% (3.2%-22.1%), 8.1% (6.3%-9.8%), and 4.4% (2.3%-6.5%), respectively. After multivariate adjustment, the risk of prediabetes, IFG, IGT, and IFG complicated with IGT increased with the increment of blood pressure (both P for trend <0.05). The positive dose-response relationships between blood pressure levels and risk of prediabetes were also significant among male, urban, and rural residents (both P for trend <0.05), and the interactions between sex and blood pressure showed significant associations for risk of prediabetes and IGT (both P for interaction <0.05). Conclusions: Higher blood pressure levels were associated with an increased risk of prediabetes. The association with prediabetes was stronger in males, but no significant difference was found between urban and rural residents. More distinctive and effective prevention and control strategies should be developed for different populations.

[Evidence summary for postoperative hypothermia rewarming in adults with severe burns].

Objective: To retrieve, evaluate, and summarize the best evidence for postoperative hypothermia rewarming in adults with severe burns. Methods: Foreign language databases including Cochrane Library, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Ovid-Medline, BMJ Best Practice, and Web of Science were retrieved with the search terms of " severe burn/major burn/severe degree burn" , " hypothermia/warming intervention/hypothermia/temperature/body temperature change" , and " postoperative /perioperative/peri-operative/post-operative" and Chinese databases including Chinese Journal Full-Text Database, Wanfang Database, and VIP Database were retrieved with the search terms of "//" , "/" , and "" to obtain all the publicly published evidence for postoperative hypothermia rewarming in adults with severe burns from the establishment of each database to April 2018, including systematic evaluations, guidelines, expert consensus, evidence summary, and original research closely related to the evidence. The literatures were screened and evaluated for their quality, the evidences were extracted from them, evaluated, classified in order to summarize the best evidences. Results: A total of 8 literatures were included, including one systematic evaluation, three guidelines, one expert consensus, and three evidence summaries. Finally, the best evidences in 8 aspects including the body temperature monitoring site, body temperature monitoring frequency, surface heating, in vivo heating, rewarming start, multi-strategy rewarming, equipment, and personnel training were summarized. Conclusions: Based in the evidence-based nursing method, this study retrieves and evaluates the literature, summarizes the evidence analysis and evaluation, and obtains the best evidences of postoperative hypothermia rewarming in adult patients with severe burns, which provides a strong reference for the clinical implementation of rewarming.

[Nursing care of 29 central venous catheterizations for one burn patient with 99% total body surface area].

On February 6, 2017, one male patient aged 25 years with total burn area of 99% total body surface area (TBSA) and full-thickness burn area of 95% TBSA was transferred from a primary hospital to the Second Affiliated Hospital of Zhejiang University School of Medicine one day post injury. On admission, the patient was clearly conscious, with tracheotomy ventilator assisted ventilation, and received rehydration, antishock, anti-infection, nutritional support, debridement, skin grafting, and negative pressure treatment. During the hospitalization, the patient was in critical condition and 28 central venous catheterizations and 1 peripherally inserted central catheter were performed.Based on multidisciplinary cooperation and on the premise of full risk assessment, nurses focused on strengthening the nursing of central venous catheter related infection. The measures for central venous catheter care were improved after detection of carbapenems resistant Klebsiella pneumoniae from catheter tip attachment, wound exudate, and blood culture, active prevention measure targeted at thrombosis around central venous catheter was performed, and prevention of unplanned extubation was emphasized during the use of rotating bed, soaking bath, and agitation of patient. On the 171st day of admission, peripherally inserted central venous catheter was performed by intravenous therapy nurse specialist on the scar formation site of the right upper arm. The catheter was withdrawn after indwelling for 55 days and the patient recovered and was discharged. During follow-up of 18 months, the patient recovered well.

[Nursing of one patient with extremely severe burn-blast combined injury complicated with acute kidney injury caused by dust explosion].

On January 31, 2018, a 21-year-old male patient with extremely severe burn-blast combined injury complicated with acute kidney injury caused by dust explosion of crospovidone was admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine. The following nursing measures were carried out, aiming at the condition of the patient. We strengthened the management of fluid intake and output volume, prevented hypothermia and unplanned disembarkation during the period of continuous renal replacement therapy with burn shock and acute kidney injury. For traumatic pneumothorax, we took a good care of the closed chest drainage tube and implemented a ventilation strategy of low tide and low positive end expiratory pressure. During the infection with carbapenem-resistant Klebsiella pneumoniae, the environmental disinfection of the care unit was optimized and polymyxin B drug care was done. After 71 days of comprehensive treatment and nursing care, the patient recovered and was discharged from hospital. This case suggests that, in view of the renal function and lung function of patients with extremely severe burn-blast combined injury, individualized treatment and nursing measures are helpful to improve the cure rate and prognosis.

[Nursing care of one patient with neuromyelitis optica spectrum disorders complicated with pressure ulcers].

On February 11, 2019, a 37-year-old female patient with neuromyelitis optica spectrum disorders was admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine, and her acute osteomyelitis was caused by infection of multiple pressure ulcer wounds with Staphylococcus aureus. The patient was diagnosed and treated with multidisciplinary cooperation. The nurses focused on the strict observation of the syndrome of neuromyelitis optica spectrum disorders during hormone reduction therapy, guarded against the rebound of condition, implemented wound care in stages according to the diagnosis and treatment plan, maintained effective drainage, ensured appropriate negative pressure, and strengthened nutrition to promote wound healing. After active treatment and careful nursing care, the patient recovered and was discharged on the 39th day after admission.

[Practice of nosocomial infection management in burn department based on the American hospital evaluation standard of the Joint Commission International].

Objective: To explore the role of continuous quality improvement measures based on the American hospital evaluation standard of the Joint Commission International (JCI) in prevention and control of nosocomial infection in Burn Department of the Second Affiliated Hospital of Zhejiang University School of Medicine (hereinafter referred to as the author' s department). Methods: From 2013 to 2018, based on 11 JCI standards related to infection prevention and control and the current situation of the author' s department, more than 50 doctors, nurses, and nursing assistants from the author' s department participated in continuous improvement of the three-level management system of nosocomial infection in the author' s department, focusing on implementing of management of patient with multidrug resistant bacteria infection, optimizing the infection control management of instrument and cloth, and implementing target management on 5 indicators such as hand hygiene implementation rate, and carrying out inspection, quality management, and improvement on 11 items of prevention and control of nosocomial infection. The implementation rate of hand hygiene from 2013 to 2018 and the accuracy rate of hand hygiene from 2016 to 2018 of medical staff in the author' s department, and incidences of catheter-related bloodstream infection (CRBSI) of central venous, catheter-associated urinary tract infection (CAUTI), and ventilator associated pneumonia (VAP) of burn intensive care unit in the author's department from 2013 to 2018 were monitored.The following 7 indicators were monitored from 2013 to 2018, including false negative rate of nosocomial infection, incidence of hyperglycemia during intensive insulin treatment for severely burned patients, the implementation rate of CRBSI preventive measures, the specification rate of surface fixation of indwelling catheter, the implementation rate of VAP preventive measures, the accuracy rate of bed temperature during the use of suspended bed, and the implementation rate of hand hygiene of standardized training medical staff in the author' s department before and after improvement. Data were statistically analyzed with chi-square test. Results: The implementation rate of hand hygiene of medical staff in the author' s department was 88.0%-89.5% from 2013 to 2018, the correct rate of hand hygiene of medical staff in the author' s department was 95.10%-97.35%, and both reached the target values. The incidences of CRBSI in 2015, VAP in 2017, and CAUTI in 2013, 2014, and 2017 of burn intensive care unit failed to reach the respective target value and reached the respective target value after quality improvement, and the above-mentioned 3 indicators reached the respective target value in other years. From 2013 to 2018, the false negative rate of nosocomial infection and the incidence of hyperglycemia during intensive insulin treatment of severely burned patients in the author' s department after improvement were significantly lower than those before improvement (χ(2)=24.50, 4.74, P<0.05 or P<0.01), the implementation rate of CRBSI preventive measures, the specification rate of surface fixation of indwelling catheter, the implementation rate of VAP preventive measures, and the accuracy rate of bed temperature during the use of suspended bed after improvement in the author' s department were significantly higher than those before improvement (χ(2)=13.78, 6.50, 20.37, 13.92, P<0.05 or P<0.01), and the implementation rate of hand hygiene of standardized training medical staff in the author' s department after improvement was similar to that before improvement (χ(2)=1.71, P>0.05). Conclusions: The introduction of JCI standard can improve the implementation rate and accuracy rate of hand hygiene of medical staff in burn department, reduce the incidences of CRBSI, CAUTI, and VAP, and improve the effect of prevention and control of nosocomial infection in burn department.

LncRNA MIR4435-2HG contributes into colorectal cancer development and predicts poor prognosis.

OBJECTIVE: Some studies have confirmed that long non-coding ribonucleic acids (lncRNAs) played a vital role in the pathophysiology of various diseases, especially in oncogenesis and progression of tumors. Dysexpressed lncRNAs regulate different cellular processes, including proliferation, invasion, and apoptosis. The aim of this study was to explore the clinical significance and function of lncRNA MIR4435-2HG in colorectal cancer. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression of lncRNA MIR4435-2HG. The Kaplan-Meier method was used to evaluate the overall survival and disease-free survival of patients with colorectal cancer. The cell proliferation was measured by Methyl thiazolyl tetrazolium (MTT) assay. The cell apoptotic rate was measured via flow cytometry method. RESULTS: LncRNA MIR4435-2HG is a novel cancer-related lncRNA that was recently found to exhibit high expression in colorectal cancer. The dysregulation of lncRNA miR4435-2HG was significantly related to the tumor size (p<0.001), lymph node metastasis (p<0.001), and tumor node metastasis (TNM) staging (p=0.022). The patients with higher expression of lncRNA miR4435-2HG showed worse prognosis than those with low expression of lncRNA miR4435-2HG group. Besides, the downregulated lncRNA miR4435-2HG expression could repress cell proliferation and enhance cell apoptosis. CONCLUSIONS: LncRNA MIR4435-2HG functions as an oncogene that promotes colorectal cancer progression, and likely represents a biomarker or therapeutic target of colorectal cancer.

Colorectal anastomosis after laparoscopic extended left colectomy: techniques and outcome.

AIM: After extended left colectomy, traditional colorectal anastomosis is often not feasible because of insufficient length of the remaining colon to perform a tension-free anastomosis. Total colectomy with ileorectal anastomosis could be an alternative but this can lead to unsatisfactory quality of life. Trans-mesenteric colorectal anastomosis or inverted right colonic transposition (the so-called Deloyers procedure) are two possible solutions for creating a tension-free colorectal anastomosis after extended left colectomy. Few studies have reported their results of these two techniques and mostly via laparotomy. The aim of this study was to describe the trans-mesenteric colorectal anastomosis and the inverted right colonic transposition procedure via a laparoscopic approach and report the outcome in a series of 13 consecutive patients. METHOD: This was retrospective chart review of laparoscopic colorectal surgery with trans-mesenteric colorectal anastomosis or the inverted right colonic transposition procedure from January 2015 up to 2019. An accompanying video demonstrates these two techniques. RESULTS: Thirteen consecutive patients underwent either a laparoscopic trans-mesenteric colorectal anastomosis (n = 9) or an inverted right colonic transposition procedure (n = 4). One patient had intra-operative presacral bleeding that was stopped successfully without conversion. Two patients had a postoperative intra-abdominal abscess, but no anastomotic complications were recorded. The median number of bowel movements per day after 6 months was 2 (range 2-5). CONCLUSIONS: Trans-mesenteric colorectal anastomosis or the inverted right colonic transposition procedure is feasible laparoscopically. The now well-established classical advantages of the laparoscopic approach are associated with good functional outcome after these procedures.

[One case of severe burn complicated with severe acute pancreatitis characterized by hypoglycemia].

A 44 years old male patient suffered from flame burn of 20% total body surface area was admitted to our hospital on February 14th, 2018. On admission, his abdominal CT was not obviously abnormal. Eleven hours after burn, the patient had left upper abdominal pain, accompanied by reduction of urine output. Then he suffered from sudden hypotension and hypoglycemia. Acute pancreatitis was diagnosed by abdominal CT reexamination. Low glucose level was ameliorated slowly through positive rescue, and pancreatitis crisis progressed rapidly. The family members gave up rescue care, and patient discharged. The case indicates that physicians should pay attention to glucose levels of severe burn patients, and be cautious of appearance of postburn pancreatitis.

[Treatment and nursing of one patient with burns on perineal region and complicated by secondary multiple organ injuries by exposing to paraquat fluid].

On March 18, 2016, one 53 years old man with burns on perineal region and complicated by secondary multiple organ injuries by exposing to paraquat fluid was admitted to our department. Comprehensive treatment measures including protective mechanical ventilation, intensive care, vacuum sealing drainage, anti-infection, and organ protection were conducted sequentially. Through 33 days of comprehensive treatment and nursing, the patient's condition substantially improved and he left hospital. This case presents that paraquat fluid absorption through skin and mucosa can also lead to severe systemic poisoning, and multiple organ protection is the key to improve the prognosis of this patient.

MicroRNA-125a regulates proliferation and apoptosis of acute myeloid leukemia through targeting NF-κB pathway.

OBJECTIVE: To elucidate the influence of microRNA-125a on the biological behaviors of acute myeloid leukemia (AML) cells. MATERIALS AND METHODS: MicroRNA-125a mimic and negative control (NC) were constructed and transfected into AML cell line HL60, respectively. Cell viability of HL60 cells transfected with microRNA-125a mimic or NC was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Regulatory effects of microRNA-125a on enzyme activities of B-cell lymphoma-2 (Bcl-2), Bcl-xl, caspase-3, and caspase-9 in HL60 cells were quantified by a spectrophotometry. Changes in apoptosis and invasion of HL60 cells overexpressing microRNA-125a were detected by flow cytometry and transwell assay, respectively. Protein levels of cell cycle genes (cyclin B, cdc-2, mdm-2), pro-apoptotic gene p53 and anti-apoptotic gene Bcl-2 in HL60 cells transfected with microRNA-125a mimic or NC were assessed by Western blot. Finally, the mRNA levels of Bax, caspase-8, nuclear factor-κB (NF-κB), and c-myc in HL60 cells with microRNA-125a overexpression were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RESULTS: MicroRNA-125a expression remarkably increased by transfection of microRNA-125a mimic into HL60 cells, suggesting its sufficient transfection efficacy. MTT assay revealed an inhibited viability after microRNA-125a overexpression. Transfection of microRNA-125a mimic markedly enhanced enzyme activities of caspase-3 and caspase-9, but reduced activities of Bcl-2 and Bcl-xl in HL60 cells than controls (p<0.05). Moreover, microRNA-125a overexpression elevated apoptotic rate as FCM data indicated. Transwell assay demonstrated a decrease in the invasive rate of HL60 cells overexpressing microRNA-125a. Western blot analyses revealed that cell cycle genes all downregulated by transfection of microRNA-125a mimic in HL60 cells. The protein level of p53 upregulated and Bcl-2 downregulated in HL60 cells overexpressing microRNA-125a (p<0.05). Furthermore, mRNA levels of pro-apoptotic genes Bax and caspase-8 were enhanced after microRNA-125a overexpression, while mRNA levels of NF-κB and c-myc were reduced (p<0.05). CONCLUSIONS: MicroRNA-125a inhibits proliferative and invasive potentials, arrests the cell cycle in the G2/M phase of AML cells by regulating the NF-κB pathway.

Regulation of c-fos expression by the dopamine D1-D2 receptor heteromer.

The dopamine D1 and D2 receptors form the D1-D2 receptor heteromer in a subset of neurons and couple to the Gq protein to regulate intracellular calcium signaling. In the present study the effect of D1-D2 heteromer activation and disruption on neuronal activation in the rat brain was mapped. This was accomplished using the dopamine agonist SKF 83959 to activate the D1-D2 heteromer in combination with a TAT-D1 disrupting peptide we developed, and which has been shown to disrupt the D1/D2 receptor interaction and antagonize D1-D2 heteromer-induced cell signaling and behavior. Acute SKF 83959 administration to rats induced significant c-fos expression in the nucleus accumbens that was significantly inhibited by TAT-D1 pretreatment. No effects of SKF 83959 were seen in caudate putamen. D1-D2 heteromer disruption by TAT-D1 did not have any effects in any striatal subregions, but induced significant c-fos immunoreactivity in a number of cortical regions including the orbitofrontal cortex, prelimbic and infralimbic cortices and piriform cortex. The induction of c-fos by TAT-D1 was also evident in the anterior olfactory nucleus, as well as the lateral habenula and thalamic nuclei. These findings show for the first time that the D1-D2 heteromer can differentially regulate c-fos expression in a region-dependent manner either through its activation or through tonic inhibition of neuronal activity.

3-D imaging, illustration, and quantitation of enteric glial network in transparent human colon mucosa.

BACKGROUND: Enteric glia form a network in the intestinal mucosa and have been suggested to engage in multidirectional interactions with the epithelium, blood vessels, nerves, and immune system. However, due to the dispersed nature of the glial network, standard histology cannot provide a global view of the network architecture. We prepared transparent human colon mucosa for three-dimensional (3-D) confocal microscopy with S100B immunostaining to reveal the location-dependent glial network for qualitative and quantitative analyses. METHODS: Full-thickness human colons were acquired from colectomies performed for colorectal cancer. We targeted the mucosa away from the tumor site to characterize the glial network morphology. Optical clearing (use of immersion solution to reduce scattering) was applied to generate transparent specimens for deep-tissue microscopy. KEY RESULTS: Two features of the glial network were seen: (i) A dense glial population resides at the crypt base/mucosal boundary in contact with the lymphatic vessels, and (ii) from the base, the glial network elongates along the crypt axis with peri-cryptic and peri-vascular connections toward the opening. We quantified the mucosal glia as the S100B-positive cells with at least two processes extending from the cell body. Examples of the global and in-depth imaging of adenoma were given to illustrate the morphological correlation between the loss of glial fibers and the aberrant crypts. CONCLUSIONS & INFERENCES: We have established a useful approach for 3-D imaging, panoramic illustration, and quantitation of the enteric glia in the human colon mucosa to help characterize their roles with mucosal components in health and disease.

Room temperature SnO2 thin film gas sensor fabricated on Si nanospikes.

The SnO2 thin film CO gas sensors have been fabricated on silicon nanostructured surface made using a femtosecond pulsed laser irradiation. The measurement shows a significant response to the CO gas at room temperature. While a SnO2 sensor fabricated on a flat surface shows no response when CO gas exists at room temperature. The high area/volume ratio and sharp structures of the nanospikes enhance the sensitivity of SnO2 at room temperature.

Inhibitory mechanisms of kinetin, a plant growth-promoting hormone, in platelet aggregation.

Kinetin has been shown to have anti-aging effects on several different systems including plants and human cells. The aim of this study was to examine the detailed inhibitory mechanisms of kinetin in platelet aggregation. In this study, kinetin concentration-dependently (50-150 microM) inhibited platelet aggregation in human platelets stimulated by agonists. Kinetin (70 and 150 microM) also concentration-dependently inhibited intracellular Ca2+ mobilization and phosphoinositide breakdown in platelets stimulated by collagen (1 microg/ml). Kinetin (70 and 150 microM) significantly inhibited thromboxane A2 formation stimulated by collagen (1 microg/ml) and arachidonic acid (60 microM) in human platelets. In addition, kinetin (70 and 150 microM) significantly increased the formation of cyclic AMP. Intracellular pH values were measured spectrofluorometrically using the fluorescent probe BCECF-AM in platelets. The thrombin-evoked increase in pHi was markedly inhibited in the presence of kinetin (70 and 150 microM). Rapid phosphorylation of a platelet protein of molecular weight (Mr) 47000 (P47), a marker of protein kinase C activation, was triggered by collagen (1 microg/ml). This phosphorylation was inhibited by kinetin (70 and 150 microM). In conclusion, these results indicate that the anti-platelet activity of kinetin may be involved in the following pathways: kinetin's effects may initially be due to inhibition of the activation of phospholipase C and the Na+/H+ exchanger. This leads to lower intracellular Ca2+ mobilization, followed by inhibition of TxA2 formation and then increased cyclic AMP formation, followed by a further inhibition of the Na+/H+ exchanger, ultimately resulting in markedly decreased intracellular Ca2+ mobilization and phosphorylation of P47. These results suggest that kinetin has an effective anti-platelet effect and that it may be a potential therapeutic agent for arterial thrombosis.

The hyperaggregability of platelets from normal pregnancy is mediated through thromboxane A2 and cyclic AMP pathways.

There is substantial evidence of increased platelet reactivity in vivo and in vitro during pregnancy, with the risk of developing pre-eclampsia. In this study, platelet function was studied during 28-40 weeks of gestation in a group of women who remained normotensive and in a group of nonpregnant female controls. Platelet aggregation stimulated by thrombin and adenosine diphosphate was markedly enhanced in washed platelets from pregnant subjects. Thrombin (0.04 U/ml)-evoked increases in intracellular Ca+2 mobilization of Fura 2-AM-loaded platelets were also enhanced in pregnant subjects. The binding of fluorescein isothiocyanate (FITC)-triflavin (2 microg/ml) to the glycoprotein IIb/IIIa complex in thrombin-activated platelets did not differ significantly between the nonpregnant and pregnant groups. Thromboxane A2 (TXA2) formation in both resting and thrombin-activated platelets from pregnant subjects was significantly greater than from nonpregnant subjects. Levels of cyclic adenosine monophosphate (cAMP) in both resting and prostaglandin E1-treated platelets (10 micromol/l) from pregnant subjects were significantly lower than those from nonpregnant subjects. There were no significant differences between nonpregnant and pregnant subjects in platelet cAMP levels in the presence of imidazole (600 micromol/l) and indomethacin (500 micromol/l). Intracellular pH values in platelets were measured spectrofluorometrically using the fluorescent probe, BCECF-AM. The increase in intracellular pH stimulated by thrombin (0.04 U/ml) in pregnant subjects was markedly greater than that in observed nonpregnant subjects. We conclude that the agonist-induced hyperaggregability of platelets in normal pregnancy may be due, at least partly, to stimulation of the Na+/H+ exchanger and subsequently to elevated intracellular Ca+2 mobilization, and then to increased TXA2 formation and a lowered level of cAMP, which leads to further increases in intracellular Ca+2 mobilization, and finally to enhanced platelet aggregation.

Quantification of regional myocardial wall thickening on electrocardiogram-gated SPECT imaging.

BACKGROUND: Current assessment of regional left ventricular function with electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT) imaging is generally performed by visual inspection. The objective of this study was to develop and validate a new computer algorithm for quantifying regional left ventricular wall thickening on ECG-gated SPECT images. METHODS: Regional wall thickening was measured from count density changes during the cardiac cycle observed in 24-sector circumferential count distribution profiles generated from each of 8 frames of an ECG-gated SPECT study. Wall thickening was expressed as the percent count increase during systole relative to end diastole. The program was tested in a phantom simulation and in patient studies consisting of a pilot study (n = 40) and a validation study (n = 33). In the phantom study varying degrees of wall thickening were simulated. The pilot study included 20 normal subjects with low likelihood (<3%) of coronary disease and 20 patients with prior myocardial infarction. Mean wall thickening - 2 standard deviations, measured in normal subjects, defined the lower limit of normal wall thickening. This criterion was tested in the validation study in 13 normal subjects and 20 patients with prior myocardial infarction. Abnormal wall thickening was characterized by extent (percent of circumferential profile) and severity (minimal thickening). RESULTS: The phantom study showed excellent linear correlation between wall thickening computed by the new software and actual wall thickening (r = 0.98). Interobserver and intraobserver reproducibility of quantitative assessment of minimal wall thickening were excellent (r = 0.98 and 0.99, P < .001). Regional wall thickening varied considerably from apex to base in the same ventricle among normal subjects. The average lower limit of normal wall thickening was 25% to 30% at the apex, 19% to 24% in the mid-ventricle, and 13% to 20% at the base of the left ventricle. In the validation study 11 of 13 normal subjects had wall thickening profiles within the pre-defined normal range. All 20 patients with prior myocardial infarction had abnormal regional wall thickening. Minimal regional wall thickening in the infarct areas was 5.4% +/- 5.5%, compared with 30.1% +/- 9.1% wall thickening in comparable anatomic areas in normal subjects (P < .001). CONCLUSION: Regional wall thickening can be quantified reliably from regional count density changes during the cardiac cycle on ECG-gated SPECT images. The new software measured the extent and severity of abnormal regional wall thickening relative to normal files. The method is highly reproducible. Clinical validation showed good differentiation between normal subjects and patients with prior infarction. Quantification of regional wall thickening may enhance diagnostic accuracy and reproducibility of interpretation of gated SPECT imaging.