Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.

Ionic Liquid Extraction Behavior of Cr(VI) Absorbed on Humic Acid-Vermiculite.

Cr(VI) can be released into soil as a result of mining, electroplating, and smelting operations. Due to the high toxicity of Cr(VI), its removal is necessary in order to protect ecosystems. Vermiculite is applied in situations where there is a high degree of metal pollution, as it is helpful during the remediation process due to its high cation exchange capacity. The Cr(VI) contained in the vermiculite should be extracted in order to recover it and to reduce the impact on the environment. In this work, adsorption equilibrium data for Cr(VI) in a simulated sorbent for soil remediation (a mixture that included both humic acid (HA) and vermiculite) were a good fit with the Langmuir isotherm model. The simulated sorbent for soil remediation was a favorable sorbent for Cr(VI) when it was in the test soil. An ionic liquid, [C4mim]Cl (1-butyl-3-methylimidazolium chloride), was studied to determine its efficiency in extracting Cr(VI) from the Cr- contaminated simulated sorbent in soil remediation. At 298 K and within 30 min, approximately 33.48 ± 0.79% of Cr(VI) in the simulated sorbent in soil remediation was extracted into [C4mim]Cl. Using FTIR spectroscopy, the absorbance intensities of the bands at 1032 and 1010 cm-1, which were attributed to C-O bond stretching in the polysaccharides of HA, were used to detect the changes in HA in the Cr-contaminated simulated sorbent for soil remediation before and after extraction. The results showed that Cr(VI) that has been absorbed on HA can be extracted into [C4mim]Cl. Using 1H NMR, it was observed that the 1-methylimizadole of [C4mim] Cl played an important role in the extraction of Cr(VI), which bonded with HA on vermiculite and was able to be transformed into the [C4mim]Cl phase.

[The diagnostic performance of galactomannan detection in invasive pulmonary aspergillosis with severe and critically ill influenza].

Objective: To analyze the diagnostic performance of serum and bronchoalveolar lavage fluid (BALF) galactomannan (GM) test in invasive pulmonary aspergillosis(IPA) with severe and critically ill influenza. Methods: A retrospective study was performed for 157 patients with severe and critically ill influenza admitted to the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from December 2017 to April 2019.Clinical characteristics and serum and BALF GM values were collected. The patients were divided into an IPA group (n=18) and a non-IPA group (n=139). The definition of IPA modified from AspICU algorithm taken as the gold standard (The corresponding clinical manifestations, imaging manifestations and microbiological diagnostic criteria should be met simultaneously), the performance of serum and BALF GM test and their combination to IPA with influenza were analyzed respectively and receiver operating characteristic curve (ROC) was drawn. Results: A total of 157 cases were enrolled, 95 were critically ill, and the mortality of IPA with influenza was 55.6%(10/18). The APACHE Ⅱ score, PSI score, urea nitrogen, influenza severity (Percentage of critically ill influenza) and invasive ventilator in IPA group were (16±6), (110±31), 10.7 (8.4, 17.8) mmol/L, 88.9% and 66.7%, respectively, which were significantly higher than those in non-IPA group [(10±5), (83±30), 5.2 (3.6, 7.6) mmol/L, 56.8% and 24.5%, P<0.05]. All patients received serum GM test and 32 patients performed BALF GM test at the same time. When the cut-off valve of serum GM test was 0.5 µg/L, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 66.7% (12/18), 95.0% (132/139), 63.2% (12/19) and 95.7% (132/138) respectively. When the cut-off value of BALF GM test was 1.0 µg/L, the sensitivity, specificity, PPV and NPV were 80%(8/10),86.4%(19/22),72.7%(8/11)and 90.5%(19/21)respectively. The BALF GM cut-off value of 0.88 µg/L showed the highest diagnostic efficacy for IPA, for which the sensitivity and specificity were 90%(9/10) and 86.4%(19/22). The areas under the ROC curve of serum GM, BALF GM, and the combination of them were 0.81, 0.85, and 0.94 respectively. The difference was statistically significant (P<0.05) and the combined diagnosis efficiency was higher. Conclusions: Critically ill influenza patients should be alert for IPA. The sensitivity of serum GM test in the diagnosis of IPA with influenza was low, while the NPV was high. The optimum BALF GM cut-off value was 0.88 µg/L. The combination with BALF and serum GM test can improve the diagnostic performance.

[Dynamic research of serum cryptococcal capsular polysaccharide antigen titer and chest CT of pulmonary cryptococcosis after antifungal therapy].

Objective: To observe the dynamic changes of serum cryptococcal capsular polysaccharide antigen (CrAg) titer and chest CT of pulmonary cryptococcosis (PC) after antifungal therapy. Methods: A retrospective study was performed for patients with PC admitted to the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from January 2015 to April 2018. Serum CrAg titers and Chest CT examination were performed for all the cases before and after treatment. The difference between immunocompetent hosts group and immunocompromised hosts group were compared and analyzed. Results: Eighty-two patients with PC including 46 male (56.1%) and 36 (43.9%) female were enrolled. Fifty-two (63.4%) patients were proven PC and thirty (36.6%) patients were probable PC. Forty-five (54.9%) patients had underlying diseases. Fifty-four (65.9%) patients were immunocompetent hosts and twenty-eight (34.1%) patients were immunocompromised hosts. The mean duration of treatment was (7.9±2.4) months and the mean follow-up was (24.0±10.0) months. Improvement (≥75%) in chest CT were found in 64.8% of the cases in immunocompetent group and 67.9% in immunocompromised group after 6 months' treatment. Improvement (≥75%) was found in 88.9% of the cases with patchy infiltrates or consolidation and only 63.0% in nodular or mass-like type and mixed patterns of PC. The serum CrAg titer of 55 cases ranged from 1∶4 to 1∶160 before treatment (median 1∶40) and decreased for all cases after treatment. The serum CrAg titer became negative in 20 cases at last. Mean time of serum CrAg titer turning negative was (11.8±8.1) months. The serum CrAg titer became negative or decreased to 1∶1 in 24 cases after treatment cessation, of whom the serum CrAg titer ranged from 1∶5 to 1∶160 before treatment (median 1∶20). The serum CrAg titer of 31 cases ranged from 1∶4 to 1∶640 before treatment (median 1∶64), of whom the serum CrAg detections were still positive after treatment cessation, and CrAg titer was 1∶10 (ranged from 1∶2 to 1∶160). Conclusions: In PC, chest CT improves after antifungal treatment, and the infiltrates or consolidation type of PC resolves faster than nodular or mass-like shadows and mixed patterns in CT. The serum CrAg titer decreases after antifungal treatment.

[Diagnostic performance of pathology, culture and ROSE of lung biopsy for suspected pulmonary infectious diseases].

Objective: To explore the diagnostic performance of CT guided percutaneous lung biopsy (PTLB) with pathology, culture and rapid on-site evaluation (ROSE) in patients with pulmonary infectious diseases. Methods: From January 2016 to June 2018, a retrospective study was implemented in the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University. Patients who received PTLB, suspected with lung infection were included. The basic information, clinical symptoms, imaging findings, diagnostic methods, complications, and changes in treatment of cases were collected. The diagnostic sensitivity of histopathology, microbial culture, and ROSE were evaluated at the same time. Results: A total of 529 cases were enrolled, including 354 males and 175 females, (59±14) years old in average. Tuberculosis was identified in 197 cases, non-tuberculosis mycobacteria (NTM) pulmonary disease in 8, cryptococcosis in 95, pulmonary aspergillosis in 27, filamentous fungal pneumonia in 3, talaromyces marneffei pulmonary infection in 3 and pulmonary candidiasis in 1, bacterial pneumonia in 39, and pathogen were unknown in 156 cases. A total of 417 cases were submitted for histopathology and microbial culture at the same time, the diagnostic value of pathology and microbial culture were 35.0% (146/417) and 45.6% (190/417), respectively. Combined pathology with microbial culture, the diagnostic value increased to 62.8% (262/417). The diagnostic accuracy of ROSE was 51.8% (71/137). The most common complication of PTLB was pneumothorax 26.1% (138/529). 56.1% (297/529) of the patients received targeted treatment after the diagnosis was confirmed, and 43.9% (232/529) maintained the original treatment. Conclusion: The pathology, microbial culture, and ROSE of PTLB have relative high diagnostic value for pulmonary infectious diseases.

Adverse health outcomes and health concerns among survivors of various childhood cancers: Perspectives from mothers.

Advanced therapies have improved outcomes and also resulted in a growing risk of long-term adverse health events. This study intends to estimate incidences of adverse health events and examine differences in adverse health events among childhood cancer survivors, and to understand the concerns of mothers after their child has completed cancer treatment. An explanatory sequential mixed-method was used. A total of 201 paediatric cancer survivors' mothers with mean age 43.6 years were recruited. Of the survivors, 12.4% experienced five or more adverse health events. The incidence of adverse health events of altered body image, fatigue and neurocognitive problems were 31.54%, 14.77% and 12.53% respectively. Among survivors, significant differences in adverse health events of pain, endocrine problems and altered body image issues were identified. Survivors receiving radiotherapy, bone marrow transplants or completing treatment after 6-10 years experienced significantly more adverse health events. Maintaining health was the greatest concern for mothers, and the qualitative reports of their concerns could be categorised: living in uncertainty, and keeping forward-looking. Childhood brain tumour survivors were identified as experiencing more adverse health events than other survivors. The need for healthcare teams to consider mothers' health concerns was highlighted.

[The diagnostic performance of galactomannan detection for invasive pulmonary aspergillosis in non-neutropenic hosts].

Objective: To evaluate the diagnostic performance of galactomannan(GM)detection in serum and BALF for invasive pulmonary aspergillosis (IPA) in non-neutropenic hosts. Methods: A pospective study was performed for 1 356 non-neutropenic hosts admitted to the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from September 2014 to October 2015. Serum GM test was performed for all, and BALF GM test for a proportion of the patients. The patients were divided into an IPA group and a non-IPA group. SPSS 20.0 was adopted for statistical analysis. Results: A total of 1 361 cases were enrolled, aging 18-96 years, with an average age of (64±15) years. There were 879 male and 477 female patients. Thirty-nine cases were diagnosed as IPA, accounting for 2.9%. For serum GM test, the sensitivity, specificity, PPV and NPV were 43.6%(17/39), 94.1%(1 239/1 317), 17.9%(17/95)and 98.3%(1 239/1 261)respectively. Ninety-six cases received serum and BALF GM tests at the same time. If the cut-off value of BALF GM test was 0.8, the sensitivity, specificity, PPV and NPV were 86.7%(13/15), 60.5%(49/81), 28.9%(13/45), 96.1%(49/51)respectively, but if the value was 1.0, the sensitivity, specificity, PPV and NPV were 86.7%(13/15), 74.1%(60/81), 38.2%(13/34), 96.8%(60/62)respectively. The ROC curve area of BALF GM, serum GM and the combined serum and BALF GM was 0.87, 0.75 and 0.90, respectively. Conclusions: The sensitivity of serum GM test in non-neutropenic hosts was low, but it had a high negative predictive value.The best BALF GM cut-off value was 1.0. The combined serum and BALF GM tests improved the diagnostic performance.

Associations of a family history of lupus with the risks of lupus and major psychiatric disorders in first-degree relatives.

BACKGROUND: Genetic factors link psychiatric disorders, particularly major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder (OCD), with systemic lupus erythematosus (SLE). Additionally, maternal SLE is a risk factor for long-term developmental problems, particularly learning disabilities, attention disorders, autism spectrum disorder (ASD) and speech disorders, in children. AIM: We aimed to determine whether first-degree relatives (FDRs) of patients with SLE have increased risks of SLE and major psychiatric disorders. DESIGN AND METHODS: Using the Taiwan National Health Insurance Research Database, we recruited 40 462 FDRs of patients with SLE as well as 161 848 matched controls. The risks of major psychiatric disorders, including schizophrenia, bipolar disorder, OCD, MDD, ASD and attention-deficit/hyperactivity disorder (ADHD), were assessed. RESULTS: The FDRs of patients with SLE had higher risks of SLE (reported as the adjusted relative risk and 95% confidence interval: 14.54; 12.19-17.34), MDD (1.23; 1.12-1.34), ADHD (1.60; 1.55-1.65), OCD (1.41; 1.14-1.74) and bipolar disorder (1.18; 1.01-1.38) compared with controls. Specifically, male FDRs of patients with SLE had higher risks of SLE and bipolar disorder, whereas female FDRs of patients with SLE had higher risks of MDD and OCD. Differences in the familial relationship (i.e. parents, children, siblings and twins) were consistently associated with higher risks of these disorders compared with controls. CONCLUSIONS: The FDRs of patients with SLE had higher risks of SLE, MDD, ADHD, OCD and bipolar disorder than the controls.

Successful treatment of gallbladder neuroendocrine carcinoma with combined chemo-radiotherapy: a case report and literature review.

Neuroendocrine tumors (NETs) occur in the bronchopulmonary system. Extrapulmonary NETs are rare and are considered to ac count for 2.5 - 5% of all NETs, with more than 60% of these tumors occurring along the gastro intestinal tract, including primary NET of the gall bladder. Pri mary NETs of the gall bladder have been classified as carcinoid, neuroendocrine carcinoma or heterogeneous carcinoma. Currently, the main treatment of neuroendocrine car ci noma re mains surgery. The role of radiotherapy and chemotherapy is undefined be cause of the paucity of data. In advanced cases, chemotherapy has been prescribed with such effective agents as cisplatin, carboplatin, etoposide and paclitaxel. Here we re port a case of a 64-year-old Taiwanese male patient with neuroendocrine carcinoma of the gall bladder who received combined chemoradiotherapy (CCRT) with cisplatin, 5- fluorouracil and leucovorin (PFL) from June 2009 un til now, and whose disease is stable. CCRT with PFL may be a possible reg i men for high-grade neuroendocrine carcinoma of the gall bladder.

Successful treatment of erlotinib-induced acute hepatitis and acute interstitial pneumonitis with high-dose corticosteroid: a case report and literature review.

Erlotinib, a kind of epidermal growth factor receptor tyrosine kinase inhibitor, is a target therapy and approved for the treatment of metastatic non-small cell lung cancer (NSCLC) and advanced pancreatic cancer. Among these EGFR-TKI agents, including gefitinib and erlotinib, the common dose-limiting toxicities are diarrhea, mucositis and skin rash (Acneform eruptions). In addition to the above adverse effects, infrequent but potentially fatal and lethal entity complications include acute interstitial lung disease (ILD) and acute hepatitis. The incidence of EGFR-TKI agents (gefitinib and erlotinib) induced acute hepatitis is rare and hepatotoxicity of EGFR-TKI agent was rarely discussed. The treatment of EGFR-TKI agents induced acute hepatitis remains uncertain and cessation medication is current policy. Here we reported a case of erlotinib induced interstitial pneumonitis and acute hepatitis with clinical appearance of hypoxemia and general weakness, treated with high dose pulse therapy and showed good recovery.

A phase II study of weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin as first-line chemotherapy in patients with locally advanced or metastatic gastric cancer.

BACKGROUND: Docetaxel plus cisplatin and 5-fluorouracil has become a new standard for treating advanced gastric cancer. However, high rates of severe neutropenia limit its application. Modification of the regimen could be the solution to get similar activity but less myelosuppression. METHODS: Patients with histologically confirmed, locally advanced, or recurrent/metastatic gastric adenocarcinoma without previous chemotherapy were enrolled. This regimen consisted of docetaxel (Tyxan, TTY, Taipei, Taiwan) 30-min infusion at a dose of 36 mg m(-2), followed by cisplatin 30 mg m(-2) infusion over 1 h on days 1 and 8, and oral tegafur/uracil 300 mg m(-2) per day plus leucovorin 90 mg per day on days 1-14, every 3 weeks. Tumour response was evaluated after every 2 cycles of treatment. RESULTS: From August 2007 to March 2009, 45 patients were enrolled. The median age was 56 years (range: 22-75). Among the 40 patients evaluable for tumour response, one achieved a complete response, 22 had partial responses and 11 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 58% (95% CI: 41-74%) and 53% (95% CI: 38-68%), respectively. The disease control rates in these populations were 85% (95% CI: 70-94%) and 82% (95% CI: 68-92%), respectively. In the ITT analysis, the median time to progression and overall survival were 6.8 and 13.9 months, respectively. Major grade 3-4 toxicities were neutropenia (51%), anaemia (22%), diarrhoea (16%), and infections (20%). No patient died of treatment-related toxicities. CONCLUSION: Concurrent weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin are effective and well tolerated in the treatment of advanced gastric cancer.

Acute interstitial pneumonitis in a patient receiving a FOLFOX-4 regimen plus cetuximab treated with pulse therapy.

We report a case of acute interstitial pneumonitis and respiratory failure occurring in a 69-year-old, previously healthy patient receiving FOLFOX regimen plus cetuximab for colon cancer. Association between this chemotherapy regimen and interstitial pneumonitis is rarely reported in the literature. We treated the patient with pulse steroid therapy, and improvement in respiratory function and decreased pulmonary infiltrations demonstrated good response to steroids use. However, the patient ultimately expired from respiratory complications after 98 days from admission, possibly due to secondary infection. Both oxaliplatin and cetuximab have rarely been associated with interstitial pneumonitis, and our case may serve as an important reference for physicians notice in patients receiving these chemotherapeutic agents.

Cyclin D2 and cyclin D3 play opposite roles in mouse skin carcinogenesis.

D-type cyclins are components of the cell-cycle engine that link cell signaling pathways and passage throughout G1 phase. We previously described the effects of overexpression cyclin D1, D2 or D3 in mouse epidermis and tumor development. We now asked whether cyclin D2 and/or cyclin D3 play a relevant role in ras-dependent tumorigenesis. Here, we described the effect of cyclin D3 and cyclin D2 overexpression in mouse skin tumor development. Notably, overexpression of cyclin D3 results in reduced tumor development and malignant progression to squamous cell carcinomas (SCC). Biochemical analysis of keratinocytes shows that overexpression of cyclin D3 results in strong reduction of cyclin D2 and its associated kinase activity. Furthermore, we found that reinstatement of cyclin D2 level in the cyclin D3/cyclin D2 bigenic mice results in a complete reversion of the inhibitory action of cyclin D3. Supporting these results, ablation of cyclin D2 results in reduced tumorigenesis and malignant progression. On the other hand, overexpression of cyclin D2 results in an increased number of papillomas and malignant progression. We conclude that cyclin D3 and cyclin D2 play opposite roles in mouse skin tumor development and that the suppressive activity of cyclin D3 is associated with cyclin D2 downregulation.

EP2, a receptor for PGE2, regulates tumor angiogenesis through direct effects on endothelial cell motility and survival.

Prostaglandin E2 (PGE2), a major cyclooxygenase (COX) metabolite, plays important roles in tumor biology. We studied the role of EP2, a receptor for PGE2, in tumor angiogenesis using EP2 knockout mice. We found that deletion of the EP2 receptor impaired tumor angiogenesis and this finding was confirmed by an in vivo corneal angiogenesis model and an ex vivo aortic ring assay. To further characterize the cellular mechanisms of the EP2 receptor in angiogenesis, we isolated primary pulmonary endothelial cells (ECs) from wild-type (wt) and EP2-/- mice and observed that EP2-/- ECs exhibited defects in vascular branch formation when compared to wt ECs. In addition, EP2-/- ECs showed impaired cell motility on collagen-coated surface and they responded poorly to PGE2-induced cell migration compared to control cells. However, no difference in cell proliferation was observed between the EP2-/- and wt Ecs. In addition, EP2-/- ECs were more susceptible to apoptosis than wt cells under growth factor depletion conditions. Collectively, our data demonstrate that EP2 signaling in endothelium directly regulates tumor angiogenesis by contributing to cell survival and endothelial cell motility. Moreover, our finding suggests that EP2 is a major receptor in PGE2-mediated cell motility in ECs.

Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy.

Certain refractory neoplasms, such as glioblastoma multiforme (GBM) and melanoma, demonstrate a resistant tumor phenotype in vivo. We observed that these refractory tumor models (GBM and melanoma) contain blood vessels that are relatively resistant to radiotherapy. To determine whether the vascular endothelial growth factor receptor-2 (Flk-1/KDR) may be a therapeutic target to improve the effects of radiotherapy, we used the soluble extracellular component of Flk-1 (ExFlk), which blocks vascular endothelial growth factor binding to Flk-1 receptor expressed on the tumor endothelium. Both sFlk-1 and the Flk-1-specifc inhibitor SU5416 eliminated the resistance phenotype in GBM and melanoma microvasculature as determined by both the vascular window and Doppler blood flow methods. Human microendothelial cells and human umbilical vein endothelial cells showed minimal radiation-induced apoptosis. The Flk-1 antagonists sFlk-1 and SU5416 reverted these cell models to apoptosis-prone phenotype. Flk-1 antagonists also reverted GBM and melanoma tumor models to radiation-sensitive phenotype after treatment with 3 Gy. These findings demonstrate that the tumor microenvironment including the survival of tumor-associated endothelial cells contributes to tumor blood vessel resistance to therapy.

A regime of two intravenous injections of tranexamic acid reduces blood loss in minimally invasive total hip arthroplasty: a prospective randomised double-blind study.

Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double-blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA. In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism. The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications. This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA.

Identification of the guanine binding domain peptide of the GTP-binding site of glucagon.

Glucagon, a peptide hormone synthesized and secreted by alpha islet cells, regulates glucose homeostasis by several mechanisms. Using [gamma 32P]8N3GTP, a proven photoaffinity probe for GTP, a specific nucleotide binding site on human glucagon was detected that showed preference for GTP. Half-maximal saturation of photoinsertion into the polypeptide hormone was at 8-12 microM with either [alpha 32P]8N3GTP or [gamma 32P]8N3GTP. GTP protected photolabeling with an apparent kd of 15 microM, whereas ATP was less effective as a protector, exhibiting an apparent kd of about 30 microM. Maximal protection by GTP and ATP was over 90%. UTP, CTP, GDP, ADP, GMP, AMP, guanosine, adenosine, guanine, and adenine were much less effective protectors, indicating that binding is specific for purine nucleoside triphosphates, particularly GTP. Mg2+ at 150 microM enhanced photoinsertion (twofold), whereas at 2-10 mM, it inhibited photoinsertion. Both Ca2+ and Zn2+ at 0.2 mM decreased photoinsertion about 45%. Purification of chymotryptic and tryptic digests of photolabeled glucagon by reverse-phase high performance liquid chromatography (HPLC) revealed that the N-terminal peptide, HSQGTF, was the only peptide region covalently photomodified by [32P]8N3GTP. GTP, if present during photolysis, greatly reduced both photoinsertion into glucagon and the amount of radiolabeled peptide recovered on HPLC. The specificity of binding to the N-terminal region is suggestive of a physiological role for a glucagon-GTP complex in the mechanism of action of this hormone.

Human cervix contains functional luteinizing hormone/human chorionic gonadotropin receptors.

The upper genital tract of women contains functional LH/human chorionic gonadotropin (hCG) receptors. Whether the cervix, an anatomical continuum of the uterus and fallopian tubes, also contains these receptors has never been investigated. Multiple receptor detection techniques revealed their presence with higher levels in endocervix than in ectocervix. The receptor positive cells include stratified squamous luminal epithelium of the ectocervix, columnar epithelium, glands, blood vessels, and smooth muscle in the endocervix. Treatment of cervical tissue minces with hCG resulted in a significant increase in cAMP levels and a decrease in cyclooxygenase-2 protein levels in endocervix, but not in ectocervix. In summary, human cervix contains functional LH/hCG receptors, which suggests that LH during the menstrual cycle and hCG during pregnancy may regulate cervical functions.

Evaluation of the Behring Nephelometer for detection of low level urinary albumin.

Mildly increased urinary albumin excretion rates and concentrations, below the quantity normally detected by conventional urinary protein and albumin methods, have prognostic significance for the development of nephropathy in patients with diabetes mellitus. The authors evaluated the automated Behring Nephelometer using Behring reagents for the detection of low level urinary albumin. Within run coefficients of variation (CVs, N = 20) are 1.7%, 1.3%, and 2.4% at mean urinary albumin levels of 16, 70, and 217 mg/L, respectively. Between run CVs (N = 20) are 4.5%, 2.6%, and 4.4% at mean albumin levels of 19, 71, and 239 mg/L, respectively. The method is sensitive to 3 mg/L. Hemoglobin, immunoglobulins, bilirubin, urea, and radiographic contrast media beyond a few hours of injection show no significant interference at levels normally expected from clinical specimens. Analysis is unaffected by pH within the physiologic range. Most urine specimens are stable for at least eight days when refrigerated at 4 degrees C. Specimen centrifugation before analysis is essential to avoid a negative bias that occurs when analyzing uncentrifuged refrigerated samples. Preanalytical freezing produces results higher than those observed in fresh or refrigerated samples. The authors conclude that automated nephelometry using the Behring Nephelometer is a convenient, simple, and accurate technique for the determination of low level urinary albumin.

Initial experience with a modification of the follicle aspiration, sperm injection, and assisted rupture technique.

OBJECTIVE: To establish cycle fecundity with a modification of the follicle aspiration, sperm injection, and assisted rupture (FASIAR) technique. DESIGN: Prospective, observational study. SETTING: University and health maintenance organization-based infertility centers. PATIENT(S): Infertile couples were enrolled from our professional practices. All patients were 16-18 mm in diameter by transvaginal ultrasonography. A modified FASIAR procedure was performed 22 to 28 hours after hCG injection. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): No clinical pregnancies were observed with the modified FASIAR technique. CONCLUSION(S): The FASIAR technique is still an attractive and economical technique. Our modification of the FASIAR technique, however, resulted in a suboptimal cycle fecundity.