Evaluation of the rectal V30 parameter in patients diagnosed with postoperative endometrial cancer

BackgroundThe present paper reports on analysis of 184 patients who were diagnosed with endometrial cancer. The main objective of this study was to address parameter V_rec(30Gy) which determines a volume of the rectum irradiated with a dose of 30 Gy during radiotherapy.Materials and methodsAll patients were irradiated with an IMRT technique on linear accelerators. The planning target volume (PTV) contour was determined by a radiation oncologist. The clinical target volume (CTV) was drawn on CT images obtained in a prone position. For statistical analysis, appropriate tests (e.g. the Shapiro-Wilk, Wilcoxon) were used.Results and discussionThe performed analysis showed that the recommended condition for V_rec(30Gy) is met only in 3% of patients and the observed median value exceeds 90%. The obtained results were compared with the studies in which the V_rec(30Gy) values were related to various radiotherapy techniques.ConclusionsThe analysis showed that the condition for V_rec(30Gy) is satisfied in the case of only 3% of patients. Due to the difficulty with meeting the condition, it should be reconsidered based on real results.     

Erythrocyte hyperaggregation in obesity: determining factors and weight loss influence

Objective: To compare erythrocyte aggregation (EA) in patients with severe obesity without other cardiovascular risk factors with a control group, using the Myrenne and the Sefam aggregometers, and to evaluate the effect of weight loss on this parameter. Research Methods and Procedures: This was a longitudinal, clinical intervention study of a very low‐calorie diet for 4 weeks followed by a low‐calorie diet for 2 months. In 67 severely obese patients, an anthropometric and analytical evaluation [plasmatic lipids, fibrinogen (Fbg), and EA] was performed at baseline and 3 months after diet. The same determinations were performed in 67 normal‐weight volunteers. EA was measured with the Myrenne MA₁, which determines EA at stasis (EA₀) and at a low shear of 3 seconds^?1 (EA₁), and the Sefam aggregometer, which determines aggregation index at 10 seconds^?1 (IA₁₀), aggregation time (Ta), and disaggregation threshold (γD). Insulin resistance (IR) was calculated by homeostasis model assessment. Results: Obese patients showed higher Fbg levels, EA₀, EA₁, IA₁₀, and γD values, and lower Ta values. Differences between obese patients and control group for EA₀, EA₁, Ta, IA₁₀, and γD disappeared after adjusting for BMI or for homeostasis model assessment but were maintained after adjusting for Fbg or low‐density lipoprotein‐cholesterol. Obese patients with IR showed higher EA₀ and EA₁ values. After weight loss, EA₁ showed a significant improvement. Discussion: Obese patients show increased EA. Erythrocyte hyperaggregation does not seem to be related to a high Fbg level or to an abnormal lipid profile but to IR. Hyperagreggation improves after weight loss.     

Serum prostaglandin F2α concentration in the carcinoid syndrome

Using specific radioimmunoassay procedures we measured prostaglandin F₂α (PGF₂α) and 13, 14-dihydro-15-keto prostaglandin F₂α (PGF₂α metabolite) in 12 patients with carcinoid tumors. Although PGF₂α and PGF₂α metabolite were each modestly elevated in 17% of the patients the magnitude of the elevation did not correlate with the symptoms of the carcinoid syndrome. The 24 hour urinary 5-hydroxyindoleacetic acid excretion showed a good correlation with carcinoid symptoms while the serum serotonin concentration showed a fair correlation with carcinoid symptoms. We conclude that serum elevation of PGF₂α is not a frequent occurrence in patients with the carcinoid syndrome.     

Preferential recognition of epitopes on peroxynitrite-modified alpha-2-macroglobulin by circulating autoantibodies in rheumatoid arthritis patients

Abstract

Autoimmune responses against post-translationally modified antigens are a hallmark of several autoimmune diseases. In this work, we have studied the changes in alpha-2-macroglobulin (α₂M) upon modification by peroxynitrite. Furthermore, we have evaluated the immunogenicity of modified α₂M in experimental rabbits and rheumatoid arthritis (RA) patients. Peroxynitrite-modified α₂M showed disturbed microenvironment and altered aromatic residues under UV and fluorescence studies. Aggregation, reduction in β-sheet content, production of nitrotyrosine and shift in amide I and II bands were observed in the modified α₂M by polyacrylamide gel electrophoresis besides CD and FTIR spectroscopic analysis. The exposure of hydrophobic clusters and changes in contact positions were observed in ANS and ThT binding assays. Immunological studies using ELISA showed peroxynitrite-modified α₂M as highly immunogenic producing high titre of specific antibodies in immunized rabbits. Cross-reactivity studies revealed the polyspecificity of the elicited antibodies. Direct binding ELISA and competitive inhibition studies confirmed the presence of circulating antibodies in the sera of RA patients having high specificity towards the peroxynitrite-modified α₂M as compared to the native α₂M. Sera from healthy (normal) human subjects showed lower binding with the native and modified protein. This study confirms that peroxynitrite induces structural modifications in α₂M and makes it immunogenic. The presence of neo-antigenic determinants on modified α₂M with enhanced binding for circulating autoantibodies in RA patients could offer new possibilities for diagnosis and etiopathology of the disease.

Communicated by Ramaswamy H. Sarma     

The effect of sodium bicarbonate on a single dose of diethylcarbamazine therapy in patients with bancroftian filariasis in Kenya

An attempt was made to examine the effect of a combination of diethylcarbamazine citrate (DEC-C) and sodium bicarbonate (NaHCO₃) on the pharmacokinetics of diethylcarbamazine (DEC), side-reactions and reduction of the microfilarial density of patients with Wuchereria bancrofti infection at a hospital in Nairobi, Kenya. The microfilariae carriers received DEC-C at 6 mg/kg or 3 mg/kg with or without NaHCO₃ at 75 mg/kg body weight. The patients treated with a combination of drugs showed alkaline urine for 4 h post-treatment, while patients treated with DEC-C alone showed acidic urine. Although no significant difference was detected in the DEC half-life value and other pharmacokinetic parameters between patients treated with DEC-C (6 mg/kg) plus NaHCO₃ (75 mg/kg) and those treated with DEC-C (6 mg/kg) alone, the general tendency was that in patients receiving NaHCO₃ the first-order elimination rate constant decreased and serum elimination half-life and area under the serum concentration-time curve values increased. There was a significant difference between the mean values of the first-order absorption rate constant, the first-order elimination rate constant, and the time to maximum serum concentrations for the patients receiving DEC-C at 3 mg/kg plus NaHCO₃ at 75 mg/kg and those for the group receiving DEC-C at 6 mg/kg alone. There was no difference in frequency and severity of the side-reactions between patients receiving DEC-C at 6 mg/kg plus NaHCO₃ at 75 mg/kg, DEC-C at 3 mg/kg plus NaHCO₃ at 75 mg/kg, and DEC-C at 6 mg/kg alone. During the initial 5 days post-treatment, there was no significant difference in reduction of microfilarial density among these three groups. In the field, an attempt was made to examine the possibility of increased antifilarial effect using a combination of DEC-C and NaHCO₃. The patients were examined for microfilariae, given DEC-C at 6 mg/kg with or without NaHCO₃ at 75 mg/kg, and examined for microfilariae again 1 year later. Although the cure rate was the same among the groups, the percentage reduction in microfilarial density of the patients receiving DEC-C plus NaHCO₃ was significantly greater than those of patients receiving DEC-C alone. A combination of DEC-C with NaHCO₃ will be of practical value in a single dose of DEC-C for the mass-treatment of bancroftian filariasis.     

Abnormal ganglioside accumulation in cultured fibroblasts from patients with mucolipidosis IV.

Extracts of cultured skin fibroblasts derived from patients with mucolipidosis IV showed a marked increase and altered distribution of GM₃ and GD₃ gangliosides. GD₃ is elevated 1.5–2 times that of normal whereas GM₃ is elevated to a lesser extent. No abnormalities were found in the neutral glycolipids. These two gangliosides apparently comprise most of the accumulated lipid-like material observed on ultrastructural analysis in this disease.     

Vitamin B12 Status in Pregnancy among Immigrants to Britain

Haemoglobin, serum vitamin B₁₂, and serum and red cell folate levels have been measured in 322 pregnant immigrant women in London at their first booking and in a proportion at 34 weeks of gestation and postnatally. The Indian, East-African Indian, and Pakistani and Bangladeshi patients showed significantly lower initial mean serum vitamin B₁₂ levels than the European group, the levels being lower in Hindu and Sikh patients than in Moslems. The patients of West Indian, Indian, and East-African Indian origin showed significantly lower initial mean haemoglobin levels than the immigrants from European countries. Though there was no overall correlation between haemoglobin and serum vitamin B₁₂ level the incidence of hypersegmented polymorphs and macrocytosis in the peripheral blood was highest in the Indian and East-African Indian patients, and both these features were particularly frequent in patients with subnormal serum vitamin B₁₂ levels. Only one patient, however, had overt megaloblastic anaemia due to vitamin B₁₂ deficiency. The Indian patients whose red cell folate levels were less than 200 ng/ml also had a lower mean serum vitamin B₁₂ level than those with red cell folate levels greater than 200 ng/ml. The Indian patients had smaller babies than the Europeans but this was not related to the differences in vitamin B₁₂ status between the two groups. However, out of 39 babies of the Indian group 5 (13%) showed subnormal serum vitamin B₁₂ levels in the first 10 days of life, the lowest level being 120 pg/ml.Though there was an overall statistically significant fall in serum vitamin B₁₂ between first booking and 34 weeks of pregnancy there was no significant fall in serum vitamin B₁₂ in those who initially had subnormal levels. Thus many Indian women are vitamin B₁₂ deficient in pregnancy, and this is associated with morphological blood abnormalities in many cases, but megaloblastic anaemia due to this deficiency is relatively infrequent.     

Evaluation of the Double Agar Gel Immunodiffusion Test and of the Enzyme-Linked Immunosorbent Assay in the Diagnosis and Follow-Up of Patients with Chronic Pulmonary Aspergillosis

The diagnosis of chronic pulmonary aspergillosis (CPA) depends on the radiologic image and the identification of specific antibodies. The present study aimed to evaluate accuracy parameters of enzyme-linked immunosorbent assay (ELISA) and of the determination of serum galactomannan level in the diagnosis of patients with CPA, comparing these results with the double agar gel immunodiffusion (DID) test. In addition, the prevalence of cross-reactivity and the serological progression after treatment were evaluated by comparing DID and ELISA. Six study groups were formed: G1: 22 patients with CPA, 17 of whom had Aspergillus fungus ball, one chronic cavitary pulmonary aspergillosis (CCPA) and four chronic fibrosing pulmonary aspergillosis (CFPA); G2: 28 patients with pulmonary tuberculosis (TB); G3: 23 patients with histoplasmosis (HST); G4: 50 patients with paracoccidioidomycosis (PCM); G5: 20 patients with cryptococcosis (CRC); and G6: 200 healthy controls. Serum antibodies were measured by DID and ELISA, with two antigen preparations—Aspergillus fumigatus (DID₁, ELISA₁) and a pool of A. fumigatus, A. flavus and A. niger antigens (DID₂, ELISA₂). The Platélia Aspergillus Enzyme Immunoassay (EIA) kit was used to measure galactomannan. The cut-off points of ELISA were determined for each antigen preparation and for the 95% and 99% confidence intervals. Despite the low sensitivity, DID was the technique of choice due to its specificity, positive and negative predictive values and positive likelihood ratio–especially with the antigen pool and due to the low frequency of cross-reactivity. ELISA₁ and a 0.090 cut-off showed high sensitivity, specificity and negative predictive value, but a high frequency of cross-reactivity with CRC. The best degree of agreement was observed between ELISA₁ and ELISA₂. The detection of serum galactomannan showed high sensitivity, comparable to ELISA₂. The immunodiffusion test showed an excellent relationship with the progression after treatment, which made it the reaction of choice for patient follow-up.     

Bronchial Hyperreactivity to Prostaglandin F2α and Histamine in Patients with Asthma

The influence on airway conductance of inhaled aerosols of prostaglandin F₂α (PGF₂α), histamine, and prostaglandin E₂ (PGE₂) was studied in 10 patients with spirometrically reversible bronchial asthma and in 10 healthy subjects with no history of lung disorder. Both groups responded with bronchoconstriction after inhalation of PGF₂α but the asthmatic patients were about 8,000 times more sensitive to the compound than were the healthy controls. In the patients, but not in the controls, PGF₂α often caused a long-standing decrease in airway conductance with symptoms resembling allergen-provoked asthmatic attacks. On the other hand, the patients showed less than a 10-fold increase in sensitivity to histamine, and the ratio of histamine: PGF₂α doses causing a 50% decrease of airway conductance was 2·6:1 and 2,400:1 in controls and patients respectively. Inhalation of PGE₂ while moderately but consistently increasing airway conductance in controls, had a variable—occasionally slight bronchoconstrictive—effect in patients. The decrease in airway conductance by a given dose of PGF₂α was little modified by the simultaneous inhalation of a 100-times higher PGE₂ dose. It is suggested that endogenous, locally formed PGF₂α may play an important part in the pathogenesis of bronchial asthma.     

Unsaturated free fatty acids: a potential biomarker panel for early detection of gastric cancer

Abstract

Changes in the levels of free fatty acids (FFAs) are closely associated with physiological status. Serum levels of C_16:1, C_18:3, C_18:2, C_18:1, C_20:4, and C_22:6 in 164 gastric cancer (GC) patients and 111 benign gastric disease (BGD) patients were significantly decreased compared with 252 healthy controls. Receiver operating characteristic analysis showed that the biomarker panel including C_16:1, C_18:3, C_18:2, C_20:4, and C_22:6 presents a high diagnostic ability to differentiate early-stage GC patients from healthy controls plus BGD patients, with a sensitivity of 80.6% and a specificity of 72.7%.     

Correlation between Long-acting Thyroid Stimulator Protector Level and Thyroid 131I Uptake in Thyrotoxicosis

Out of 50 consecutive untreated patients with diffuse toxic goitre 15 showed long-acting thyroid stimulator (LATS), 30 showed LATS protector only, and five showed neither. LATS protector was present in all the patients with LATS. Infiltrative ophthalmopathy was less common in patients with LATS protector only (40%) than in patients with LATS also (67%), but the difference was not significant. There was a correlation between LATS protector level and thyroid ¹³¹I uptake rate factor (k₁), the coefficient (r) being 0·68 (P < 0·001). LATS level showed no such correlation. The results support the hypothesis that LATS protector is a pathogenic thyroid stimulator in patients with diffuse toxic goitre.     

Increased production of tumor necrosis factor and prostaglandin E2 by monocytes in cancer patients and its unique modulation by their plasma

Summary We investigated the role of monocytes in the production of tumor necrosis factor (TNF) and prostaglandin E₂ (PGE₂) in 77 cancer patients with malignancies of the digestive tract, using 30 normal individuals and 18 noncancer patients as controls. Monocytes were incubated with lipopolysaccharide for 20 h, and TNF production and PGE₂ production were analyzed by bioassays. Elevated levels of TNF (>512 U/ml) and PGE₂ (>8 ng/ml) production were demonstrated in many cancer patients when these factors were induced in the medium with 10% fetal bovine serum. The elevated level of TNF was seen to be restricted for the most part to patients with malignancies. Thus, 51 out of 59 cancer patients (86%), consisting of 44 primary cancer patients and 15 recurrent cancer patients, showed an increased level of TNF. In contrast, almost all of 18 postoperative cancer patients showed TNF levels comparable to those of normal individuals. Furthermore, 16 primary cancer patients were also demonstrated to have reduced levels of TNF production by monocytes after curative operation. When 10% cancer-patient plasma was added to the induction culture, TNF production by monocytes was drastically suppressed in the cancer patients. Interestingly, the same addition of plasma induced a prominent enhancement of PGE₂ production in the cancer patients. The plasma of noncancer patients did not modulate production of these factors. No TNF activity was found in the plasma of cancer patients, but such plasma did contain an increased level of PGE₂ (100–300 pg/ml). Although PGE₂ (>2ng/ml) was able to suppress TNF production by monocytes, the addition of 10% plasma PGE₂ was not enough to induce suppression. An unknown factor(s) in the plasma of cancer patients may uniquely modulate the elevated TNF and PGE₂ production in these patients.     

Early defect of transforming growth factor β1 formation in Huntington’s disease

A defective expression or activity of neurotrophic factors, such as brain‐ and glial‐derived neurotrophic factors, contributes to neuronal damage in Huntington’s disease (HD). Here, we focused on transforming growth factor‐β (TGF‐β₁), a pleiotropic cytokine with an established role in mechanisms of neuroprotection. Asymptomatic HD patients showed a reduction in TGF‐β₁ levels in the peripheral blood, which was related to trinucleotide mutation length and glucose hypometabolism in the caudate nucleus. Immunohistochemical analysis in post‐mortem brain tissues showed that TGF‐β₁ was reduced in cortical neurons of asymptomatic and symptomatic HD patients. Both YAC128 and R6/2 HD mutant mice showed a reduced expression of TGF‐β₁ in the cerebral cortex, localized in neurons, but not in astrocytes. We examined the pharmacological regulation of TGF‐β₁ formation in asymptomatic R6/2 mice, where blood TGF‐β₁ levels were also reduced. In these R6/2 mice, both the mGlu2/3 metabotropic glutamate receptor agonist, LY379268, and riluzole failed to increase TGF‐β₁ formation in the cerebral cortex and corpus striatum, suggesting that a defect in the regulation of TGF‐β₁ production is associated with HD. Accordingly, reduced TGF‐β₁ mRNA and protein levels were found in cultured astrocytes transfected with mutated exon 1 of the human huntingtin gene, and in striatal knock‐in cell lines expressing full‐length huntingtin with an expanded glutamine repeat. Taken together, our data suggest that serum TGF‐β₁ levels are potential biomarkers of HD development during the asymptomatic phase of the disease, and raise the possibility that strategies aimed at rescuing TGF‐β₁ levels in the brain may influence the progression of HD.     

Gas Production by Intestinal Microflora of Lactose Maldigesters

To investigate whether the gas produced by faecal contents of lactose maldigesters is traceable to symptoms of intolerance we analysed by gas chromatography faecal extracts of frozen stool samples for their gas composition. The samples were taken from 21 patients with biopsy-proven hypolactasia, 10 with severe and 11 with mild symptoms (cumulative score), and were incubated in three different carbohydrate broths. After incubation, H₂, CO₂, air and methane contents were analysed in triplicate. Differences between patient groups with mild and severe symptom scores were found, but they did not reach statistical significance. Substantial intragroup variations in gas production among patients with severe (range of H₂in galactose: 0.9–8.3%, and range of CO₂: 5.9–15.9%) as well as with mild symptoms (H₂: 0–8.3%, and CO₂1.4–14.5%) were recorded. Two patients with severe and one with mild symptoms produced detectable amounts of methane. The individual symptoms, i.e. flatulence or abdominal pain, did not directly correlate with gas production, but abundant gas production had a tendency to associate with a greater difference in waistline measurements before and after lactose provocation. Preliminary comparisons between faecal H₂and CO₂production and bacterial groups isolated from the samples showed that high concentrations of Escherichia coli tended to be more often associated with high gas production. Numbers of lactobacilli and H₂concentrations showed a trend towards negative correlation.     

Biomarkers of Alzheimer′s Disease in the Cerebrospinal Fluid of Spanish Patients With Mild Cognitive Impairment

The study of biomarkers in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) is a technique used with increasing frequency in the early diagnosis of Alzheimers disease (AD). Our objectiv was to gain an own experience while evaluating the reliability, sensitivity, and reproducibility of this technique in Spanish patients. Thirty-seven patients with MCI and twenty-four control subjects were studied by means of AD biomarker analysis in CSF. xMAP Luminex and INNO-BIA Alzbio3 reagents of Innogenetics were used. The study variables assessed were levels of Aβ_1–42, T-tau and P-tau_181p proteins as well as the ratios of T-tau/Aβ_1–42 and P-tau_181p/Aβ_1–42. Samples from nineteen patients were examined twice. Intra-class correlation coefficients for the three biomarkers used showed values higher than 0.95. We observed significant differences between the control group and the MCI groups. In the 6 months following lumbar puncture (LP), eleven (29%) patients with MCI developed AD. These patients showed significant lower levels in Aβ_1–42 protein (276.35 ± 78 vs. 367.13 ± 123.49, P < 0.03) and higher ratios (T-tau/Aβ_1–42 [0.38 ± 0.2 vs. 0.22 ± 0.14, P < 0.01] and P-tau_181p/Aβ_1–42 [0.27 ± 0.13 vs. 0.16 ± 0.1, P < 0.008]) to those in the same group who remained stable. We obtained similar results to those in the most recent reliable literature with our ROC curves, especially with our P-tau_181p values and T-tau/Aβ_1–42 ratio in order to differentiate between control and AD groups. Our experience showed that the analysis of CSF-AD biomarkers in patients with MCI is reliable, sensitive and reproducible. In our knowledge, this is the first experience in Spanish patients.     

PETER PHAN: An MRI phantom for the optimisation of radiomic studies of the female pelvis

PurposeTo develop a phantom for methodological radiomic investigation on Magnetic Resonance (MR) images of female patients affected by pelvic cancer.MethodsA pelvis-shaped container was filled with a MnCl₂ solution reproducing the relaxation times (T₁, T₂) of muscle surrounding pelvic malignancies. Inserts simulating multi-textured lesions were embedded in the phantom. The relaxation times of muscle and tumour were measured on an MR scanner on healthy volunteers and patients; T₁ and T₂ of MnCl₂ solutions were evaluated with a relaxometer to find the concentrations providing a match to in vivo relaxation times. Radiomic features were extracted from the phantom inserts and the patients’ lesions. Their repeatability was assessed by multiple measurements.ResultsMuscle T₁ and T₂ were 1128 (806–1378) and 51 (40–65) ms, respectively. The phantom reproduced in vivo values within 13% (T₁) and 12% (T₂). T₁ and T₂ of tumour tissue were 1637 (1396–2121) and 94 (79–101) ms, respectively. The phantom insert best mimicking the tumour agreed within 7% (T₁) and 24% (T₂) with in vivo values. Out of 1034 features, 75% (95%) had interclass correlation coefficient greater than 0.9 on T₁ (T₂)-weighted images, reducing to 33% (25%) if the phantom was repositioned. The most repeatable features on phantom showed values in agreement with the features extracted from patients’ lesions.ConclusionsWe developed an MR phantom with inserts mimicking both relaxation times and texture of pelvic tumours. As exemplified with repeatability assessment, such phantom is useful to investigate features robustness and optimise the radiomic workflow on pelvic MR images.     

The effects of breathing pattern training on ventilatory function in patients with COPD

The purpose of this study was to assess the effects of a particular breathing pattern training (BPT) on forced expiratory volume during the first second (FEV₁) and forced vital capacity (FVC) in patients with chronic obstructive pulmonary disease (COPD). The subjects adjusted each breath to a target breath displayed on a video screen, by using visual feedback. This target was chosen in an individual sample recorded at rest. We used a randomized, controlled group design. Twenty patients with stable COPD, FEV₁ less than 1.5 liters, undergoing a traditional rehabilitation program were randomly assigned to the BPT group or to the control group. Each BPT subject underwent 30–35 training sessions spread out over four weeks, in addition to the traditional program. FEV₁ and FVC were performed before and after this program. ANOVAs showed that FEV₁ and FVC significantly improved in BPT subjects, with a mean percent increase of 22% and 19%, respectively. Corresponding changes in controls were not significant. This study showed short-term increases in FEV₁ and FVC in COPD patients practicing BPT in addition to respiratory rehabilitation, in comparison with controls. Further studies should incorporate outcome data to clarify the mechanisms and the duration of this effect.The authors express their gratitude to Philippe Carrias, Elizabeth Maclet, Françoise Tulane, and Bernard Cossalter for their contribution to this study, as well as to Michèle Delaire for her technical assistance.     

Pharmacotherapeutics of prostaglandin E2 and 15 (S) 15-methyl prostaglandin F2α in chronic schistosomal bladder ulcer: A clinico-endoscopic study

The pharmacotherapeutic effects of prostaglandin E₂ (PGE₂) and 15 (S) 15-methyl PGF_2α given by different routes of administration, were studied in 20 normal persons and 100 patients with chronic schistosomal bladder ulcer in comparison to normal saline and antimony dimercaptosuccinate drug. Prostaglandins produced a rapid significant amelioration in the ulcer symptom complex with a good percentage of ulcer disappearance on cystoscopy, while the antimony dimercaptosuccinate treated group showed a less early response which improved with follow up. This was in contrast to prostaglandins which showed relapse in the symptom-complex in some cases after a follow up period of 2 months. The combined use of schistosomicidal drugs together with, or followed by, prostaglandins might give better results.     

AIMS65评分联合血清GAS、PGE2、BAR对急性非静脉曲张性上消化道出血患者预后的评估价值

摘要 目的：探讨AIMS65评分联合血清胃泌素（GAS）、前列腺素E₂（PGE₂）、血尿素氮/白蛋白比值（BAR）对急性非静脉曲张性上消化道出血（ANVUGIB）患者内镜下止血治疗后预后的评估价值。方法：选取2020年5月～2022年5月北京市和平里医院消化内科收治的108例的ANVUGIB患者,根据患者住院28 d内的预后分为预后不良组和预后良好组。收集患者临床资料,检测血清GAS、PGE₂水平和计算AIMS65评分、BAR。采用单因素和多因素Logistic回归分析ANVUGIB患者内镜下止血治疗后预后不良的影响因素,受试者工作特征（ROC）曲线分析AIMS65评分、GAS、PGE₂和BAR对ANVUGIB患者内镜下止血治疗后预后不良的评估价值。结果：108例ANVUGIB患者预后不良发生率为37.96％（41/108）。单因素分析显示,预后不良组年龄大于预后良好组,心率、休克指数、AIMS65评分、GAS、BAR高于预后良好组,PGE₂水平低于预后良好组（P均＜0.05）。多因素Logistic回归分析显示,年龄增加和休克指数、AIMS65评分、GAS、BAR升高为ANVUGIB患者内镜下止血治疗后预后不良的独立危险因素,PGE₂升高为其独立保护因素（P均＜0.05）。ROC曲线分析显示,AIMS65评分联合GAS、PGE₂和BAR评估ANVUGIB患者内镜下止血治疗后预后不良的曲线下面积大于AIMS65评分、GAS、PGE₂和BAR单独评估。结论：预后不良的ANVUGIB患者AIMS65评分、GAS、BAR均高于预后良好的患者,AIMS65评分联合GAS、PGE₂和BAR评估ANVUGIB患者内镜下止血治疗后预后的价值较高。     

The clinical significance of HAMA in patients treated with mouse monoclonal antibodies

Twenty-four patients were analyzed for the development of HAMA (human antimouse antibodies) after being treated with repeated doses (200–500 mg) of the mouse monoclonal antibody (MAb) 17-1A. All patients developed anti-17-1A IgG antibodies, and most of them also developed IgM antibodies. In only two patients could immune complexes be demonstrated. Allergic reactions were rare (1.9%). In an extended study, a further 19 patient were analyzed for an idiotypic response. Forty-one out of 43 patients developed antiidiotypic antibodies (ab₂), and 20 of these also antianti-idiotypic antibodies (ab₃). Ab₃ ⁺ patients responded significantly better (p=0.01) and survived longer (p<0.001) compared to ab₃ ⁻ patients. In this study, we showed that MAb 17-1A could be repeatedly given on a safe basis. The development of high titers of HAMA did not cause significant clinical problems when further repeated infusions of MAb 17-1A were given. The development of an idiotypic response also indicate that the induction of HAMA might be beneficial and not harmful to the patient.