Search PubMed⌕ Search

Biomedical subjects

W C Hop

Publications and source records attributed to W C Hop.

At least 181 records · Page 10Linked to original sources
PubMed1995

Accumulation of genetic abnormalities during neoplastic progression in Barrett's esophagus.

Sex chromosome status, ploidy, and proliferation rate were evaluated in archival material of 73 Barrett's esophagus patients (48 males and 25 females). Diagnosis in esophageal mucosa samples ranged from intestinal metaplasia with no dysplasia to invasive esophageal adenocarcinoma; also, four lymph node metastases were studied. Chromosomal and ploidy aberrations were determined by in situ hybridization with repetitive DNA probes specific for chromosomes Y, X, and 1. Proliferation index (Ki-67 protein expression) was assessed by immunohistochemistry. Proliferation rate was elevated in all stages of dysplasia and in the adenocarcinomas. Aneuploidy (hyperdiploidy) and loss of the Y chromosome correlated with the advancing stages toward neoplasia (P < 0.001) and reached high prevalences (70-100%) in high-grade dysplasia and adenocarcinoma. Abnormalities of the X chromosome were not seen. These data suggest that in Barrett's esophagus, genetic perturbations may be generated in relation to a high proliferation rate.

Adenocarcinoma↗
PubMed1995

Prostate specific antigen in a community-based sample of men without prostate cancer: correlations with prostate volume, age, body mass index, and symptoms of prostatism.

The correlation between both prostate specific antigen levels (PSA) and prostate specific antigen density (PSAD) and age, prostate volume parameters, body mass index, and the International Prostate Symptom Score (IPSS) were studied in a community-based population. A sample of 502 men aged 55 through 74 years was evaluated, excluding those with a serum PSA above 10 ng/ml, those with biopsy proven prostate cancer, and those who had previously undergone a prostate operation. PSA and PSAD did not correlate with the body mass index. Weak correlations were found between PSA and age (r = 0.25; P < 0.001), PSAD and age (r = 0.17; P < 0.001) and between PSA and the total prostate volume (r = 0.58; P < 0.001). PSA did not correlate independently with age after adjustment for volume (P = 0.22). The finding that PSAD correlates with age (r = 0.17; P < 0.001) is partly explained by the incomplete volume adjustment of PSAD which is proved by the positive correlation between PSAD and prostate volume (r = 0.26; P < 0.001). In the main target age-range for prostate cancer screening there is a poor basis for the use of age-specific reference values or volume adjustment for PSA levels in order to increase the clinical usefulness of this serum marker. Comparison of the results of the present study and studies conducted in others regions shows that there may be significant differences in PSA values per age stratum. Further studies are needed to clarify the reasons for these differences.

Aged↗
PubMed1995

Cervical metastasis from the unknown primary tumor.

A retrospective study was performed to examine the results of treatment for cervical lymph node metastases from an unknown primary between 1978 and 1988. We reviewed 66 patients treated with either surgery and/or radiotherapy (n = 41), radiation therapy and chemotherapy (n = 11), combined modality treatment with surgery (n = 8) or with management delayed to proven disease (n = 6). The male-to-female ratio was 5.6 to 1, and the median age was 64 years (range, 15-89 years). Intercurrent death-corrected 5-year survival was 50%. The most important prognostic factors were M category and involvement of supraclavicular nodes. Primary tumor was eventually discovered in 12 patients during follow-up, 6 of whom received treatment with curative intent. The most common site of primary tumor was found to be the lung (n = 5).

Adolescent↗
PubMed1995

Serum sodium levels and probability of recurrent febrile convulsions.

UNLABELLED: In a prospective study of 69 children with febrile convulsions, serum sodium levels were often lower than normal (52% had levels < 135 mmol/l). The mean level (134.4 +/- 0.4 mmol/l) was significantly lower as compared to a group of children without fever (140.6 +/- 0.4 mmol/l, n = 23) and as compared to a group with fever but without convulsions (137.6 +/- 0.6 mmol/l, n = 31). The probability of a repeat convulsion within the same febrile period appeared to be significantly related to the serum sodium level. CONCLUSION: Measurement of the serum sodium is a valuable investigation in the child with a febrile convulsion. The lower the serum sodium level, the higher the probability of a repeat convulsion. This knowledge may be of practical value in deciding whether to admit the child or allow it to return home and in advising parents or carers of the risk of a repeat convulsion.

Case-Control Studies↗
PubMed1995

Ceftazidime pharmacokinetics in preterm infants: effects of renal function and gestational age.

OBJECTIVE: The objectives of this study were (1) to determine the effects of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtration rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life. METHODS: Multiple-dose pharmacokinetics of ceftazidime (administered twice daily in a 25 or 50 mg/kg body weight intravenous dose) were evaluated in 136 preterm infants on day 3 of life. Blood samples were collected from an arterial catheter 0, 1/2, 1, 2, 4, 8, and 12 hours after the intravenous dose. An HPLC method was used to determine ceftazidime concentrations in serum. The GFR was studied simultaneously by means of the 24-hour continuous inulin infusion technique. RESULTS: The total body clearance, volume of distribution, and elimination serum half-life of ceftazidime (mean +/- SD) were 55.7 +/- 34.4 ml/hr (37.3 +/- 11.9 ml/hr/kg), 496 +/- 228 ml (350 +/- 96 ml/kg), and 6.95 +/- 2.32 hours, respectively. The mean +/- SD peak and trough levels were 114.9 +/- 39.4 and 33.9 +/- 17.8 mg/L. All infants had a serum trough level above 5 mg/L. Clearance and volume of distribution of ceftazidime and GFR increased significantly with increasing gestational age, whereas serum trough levels and serum half-life of ceftazidime decreased significantly with increasing gestational age. Ceftazidime clearance increased significantly with increasing GFR. Prenatal exposure to indomethacin resulted in significantly lower GFR values and ceftazidime clearances. CONCLUSIONS: Dosage recommendations for ceftazidime administration in preterm infants during the first week of life should be based on gestational age and GFR. Additional adjustments in dosage are indicated in preterm infants who are exposed prenatally to indomethacin.

Ceftazidime↗
PubMed1995

Initial estradiol response predicts outcome of exogenous gonadotropins using a step-down dose regimen for induction of ovulation in polycystic ovary syndrome.

OBJECTIVE: To study ovarian stimulation and response patterns during a gonadotropin step-down dose regimen for induction of ovulation by applying a decremental dose regimen in polycystic ovary syndrome (PCOS) patients. DESIGN: The present prospective study involves 28 infertile clomiphene citrate-resistant PCOS patients during gonadotropin-induced cycles using a modified step-down dose regimen (and adjuvant GnRH agonist medication). Applied gonadotropin doses included initial daily doses of 150 IU IM followed by two reducing steps (37.5 IU each) based on sonographic criteria to a final daily dose of 75 IU IM. SETTING: Anovulatory infertile women in an academic referral center. INTERVENTION: Daily blood withdrawal and transvaginal pelvic ultrasound. MAIN OUTCOME MEASURES: Serum FSH and E2 concentration and follicle growth were investigated daily during gonadotropin administration. RESULTS: An initial 2.1-fold increase in serum FSH levels was observed followed by a subsequent decrease of 10% (median) per day for 4 days. Growth of ovarian follicles was sustained and ovulation achieved (midluteal P, 11.7 +/- 1.3 ng/mL; conversion factor to SI unit, 3.180; mean +/- SD) in 22 patients. Major variability in day 3 E2 increase (range, 67 to 866 pg/mL; conversion factor to SI unit, 3.671)--not related to differences in FSH serum concentrations and without changes in follicle number and size--suggests differences in ovarian sensitivity for FSH stimulation. A strong correlation (r = 0.82) was found between day 3 E2 increase and the chance of ovulation. Moreover, E2 levels on the day of gonadotropin dose reduction predict (r = 0.68) chances of late follicular phase E2 levels exceeding 871 pg/mL (conversion factor to SI value, 3.671). CONCLUSIONS: These findings provide the endocrine basis for the concept of gonadotropin induction of ovulation using a step-down dose regimen. Initial E2 increase (before initiation of follicle growth) represent differences in ovarian sensitivity to gonadotropins and predict treatment outcome.

Buserelin↗
PubMed1995

Natural history of benign prostatic hyperplasia: appropriate case definition and estimation of its prevalence in the community.

There is no consensus about a case definition of benign prostatic hyperplasia (BPH). In the present study, BPH prevalence rates were determined using various case definitions based on a combination of clinical parameters used to describe the properties of BPH: symptoms of prostatism, prostate volume increase, and bladder outflow obstruction. The aim of this study--in a community-based population of 502 men (55-74 years of age) without prostate cancer--was to determine the relative impact on prevalence rates of the inclusion of these different parameters (and of different cutoff values for these parameters) in a case definition of BPH. There is agreement that age is the dominant determinant of BPH. However, of 28 different case definitions that were formulated, only eight gave a statistically significant increase in the prevalence of BPH with age. The highest overall prevalence of 19% (95% confidence interval [CI], 15-23%) occurred using the definition that combines a prostate volume > 30 cm3 and an International Prostate Symptom Score (IPSS) > 7. The lowest prevalence rate of 4.3% (95% CI, 2-6%) occurred using the definition that combines a prostate volume > 30 cm3, an IPSS > 7, a maximum flow rate < 10 mL/s, and the presence of a postvoid residual urine volume > 50 mL. Thus, prevalence rates depend very much on the parameters used in a case definition. Follow-up will establish which men will eventually request a workup and treatment for BPH and will help determine the best clinical definition of BPH.

Age Factors↗
PubMed1995

Directional atherectomy versus balloon angioplasty in segmental femoropopliteal artery disease: two-year follow-up with color-flow duplex scanning.

PURPOSE: Directional atherectomy is an endovascular interventional technique for excision and removal of obstructive arterial lesions. To evaluate whether atherectomy would provide better results than conventional balloon angioplasty (BA) in symptomatic femoropopliteal disease, a prospective randomized study comparing the early and late outcomes of these techniques was conducted. The rate of restenosis or occlusion was assessed by use of color-flow duplex scanning during the follow-up period. METHODS: Seventy-three patients were randomized between atherectomy (38 patients) and BA (35 patients). All patients had segmental lesions of the femoropopliteal arteries amenable to either technique. The median follow-up duration was 13 months (range 1 to 39). Follow-up comprised regular clinical and hemodynamic assessment and color-flow duplex examinations. Restenosis was defined on the basis of a peak systolic velocity ratio of 2.5 or greater, and occlusion of the treated segment was diagnosed if flow signals were absent, that is, loss of patency. RESULTS: Residual stenoses (> or = 30% diameter reduction) resulted in five patients (13%) undergoing atherectomy and three patients (9%) undergoing BA. At 1 month clinical and hemodynamic improvement by Society for Vascular Surgery/International Society for Cardiovascular Surgery criteria for lower limb ischemia was observed in 34 patients (89%) treated with atherectomy and in 34 (97%) treated with BA. By life-table analysis the cumulative rate of clinical and hemodynamic success at 2 years was 52% in patients treated with atherectomy and 87% in patients treated with BA (p = 0.06). The patency rate at 2 years of treated segments was 34% in the atherectomy group and 56% in patients treated with BA (p = 0.07). In patients with lesions greater than 2 cm, the 1-year patency rate of AT was significantly lower than BA (p = 0.03). CONCLUSIONS: Atherectomy does not result in an improved clinical and hemodynamic outcome. Furthermore atherectomy of segmental atherosclerotic femoropopliteal disease does not result in a better patency rate than BA, and, in lesions with greater length than 2 cm, the atherectomy results are significantly worse.

Aged↗
PubMed1995

Long-term prognosis of breast cancer: an analysis of 462 patients in a general hospital in south east Netherlands.

In this study the long-term prognosis was analysed of all 462 consecutive female breast cancer patients who were diagnosed and carefully staged between 1970 and 1980 in a 600-bed community hospital in Eindhoven, south east Netherlands. Follow-up of recurrence and causes of death was obtained until 1 January 1993. Observed survival rates at 5, 10 and 20 years were 66%, 45% and 32%, respectively, and the corresponding breast cancer-specific survival rates were 71%, 54% and 44%. The yearly risk for a recurrence of breast cancer after treatment steadily decreased from 10% the first year to 1% after 10 years. In a multivariate survival analysis both tumour size and nodal status appeared to be equally important prognostic factors in the first 5 years after diagnosis. After 5 years only tumour size had independent prognostic value, which was not significant any more after 10 years. In patients with a tumour size < or = 2 cm and without lymph node involvement at diagnosis, the risk for a recurrence was found to be negligible after 10 years. Those patients may be considered cured, although a search for early diagnosis of a second primary breast cancer in this group is still advisable.

Adult↗
PubMed1995

Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis.

OBJECTIVE: A randomized, controlled, multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality. SUMMARY BACKGROUND DATA: Secondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis. Controlled clinical trials to study the effect of selective decontamination in such patients are not available. METHODS: Between April 22, 1990 and April 19, 1993, 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals. Patients were entered into the study if severe acute pancreatitis was indicated, on admission, by multiple laboratory criteria (Imrie score > or = 3) and/or computed tomography criteria (Balthazar grade D or E). Patients were randomly assigned to receive standard treatment (control group) or standard treatment plus selective decontamination (norfloxacin, colistin, amphotericin; selective decontamination group). All patients received full supportive treatment, and surveillance cultures were taken in both groups. RESULTS: Fifty patients were assigned to the selective decontamination group and 52 were assigned to the control group. There were 18 deaths in the control group (35%), compared with 11 deaths (22%) in the selective decontamination group (adjusted for Imrie score and Balthazar grade: p = 0.048). This difference was mainly caused by a reduction of late mortality (> 2 weeks) due to significant reduction of gram-negative pancreatic infection (p = 0.003). The average number of laparotomies per patient was reduced in patients treated with selective decontamination (p < 0.05). Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients (6%) and transient gram-negative pancreatic infection was seen in one (2%). In both groups of patients, all gram-negative aerobic pancreatic infection was preceded by colonization of the digestive tract by the same bacteria. CONCLUSION: Reduction of gram-negative colonization of the digestive tract, preventing subsequent pancreatic infection by means of selective decontamination, significantly reduces morbidity and mortality in patients with severe acute necrotizing pancreatitis.

Acute Disease↗
PubMed1995

The International Prostate Symptom Score in a community-based sample of men between 55 and 74 years of age: prevalence and correlation of symptoms with age, prostate volume, flow rate and residual urine volume.

OBJECTIVES: To study the prevalence of symptoms of prostatism in the community and the correlation between these symptoms and age, prostate volume, flow rate and residual urine volume. SUBJECTS AND METHODS: The International Prostate Symptom Score (IPSS) was administered to a community-based population of 502 men aged between 55 and 74 years with no prostate cancer and no history of a prostate operation. Prostate volume parameters, flow rate variables and post-void residual urine volume were measured. RESULTS: Overall, 6 and 24% of the men were severely and moderately symptomatic, respectively. The results of a detailed questionnaire such as the IPSS (only 12% of the men scored 0) contrast with the men's global perception of their voiding function (82% claimed to have 'no voiding complaints'). A good correlation was found between the total symptom score and the single disease-specific quality of life question that is included in the IPSS (r = 0.74, P = 0.001). There was a weak correlation between the IPSS and total prostate volume (r = 0.19, P < 0.001), and between the IPSS and physiological measures such as peak flow rate (r = -0.18, P < 0.001) and post-void residual urine volume (r = 0.25, P < 0.001). There was a very weak correlation between the IPSS and age (r = 0.09, P = 0.04). CONCLUSIONS: The parameters used to characterize benign prostatic hyperplasia (BPH) should be considered independently because no predictions about the value of a certain parameter can be made by knowing one of the other parameter values. Symptom scores should therefore not be used as a pre-selection criterion in the determination of the prevalence of clinical BPH without taking other measures into account. The interpretation of the parameter values in a clinical setting should take the lack of correlation and the variability of the parameter values into account.

Aged↗
PubMed1995

Eliminating the need for per-operative frozen section analysis of pelvic lymph nodes during radical prostatectomy.

OBJECTIVE: To eliminate the need for per-operative frozen section analysis by using pre-operative serum prostate-specific antigen (PSA), clinical stage and Anderson biopsy grade to predict lymph node metastasis. PATIENTS AND METHODS: Between 1988 and 1994, 214 patients underwent bilateral pelvic lymphadenectomy before an intended retropubic radical prostatectomy for clinically confined prostate carcinoma. Preoperative serum PSA, clinical stage and Anderson biopsy grade were analysed to investigate whether they were able to predict the results of per-operative frozen sections of pelvic lymph nodes. RESULTS: Serum PSA level was the best predictor of a frozen section which was positive for lymph node metastasis, followed by biopsy grade. Clinical T-category combined with PSA level predicted lymph node status less well than did biopsy grade and had no additional value when combined with biopsy grade and PSA. Pre-operative serum PSA combined with biopsy grade predicted a negative frozen section result of bilateral pelvic lymphadenectomy with 95% certainty in at least 17% of patients undergoing radical prostatectomy for clinically confined prostate cancer. Frozen section analysis had a false negative rate of 4.7% when compared with histological staging. Therefore, combining those patients with an estimated 95% chance of a negative frozen section with the group of false negatives, 11 in 214 patients (5.1%) would have undergone radical prostatectomy while having micrometastases. CONCLUSIONS: Selecting men for whom the per-operative frozen section analysis could be omitted may save operating time and allow more efficient use of facilities.

Biomarkers, Tumor↗
PubMed1995

Cartilaginous airway dimensions and airflow obstruction in human lungs.

Airway wall remodeling in asthma and chronic obstructive pulmonary disease (COPD) can have a profound effect on the function of the airways. We tested the hypothesis that airflow obstruction and estimates of peripheral airway inflammation correlate with airway wall thickness and the amount of bronchial smooth muscle in cartilaginous airways. In addition, we estimated the theoretical relation between airway dimensions and airway resistance with a computational model. Lung tissue was obtained from 72 patients with different degrees of COPD who were operated on for a solitary peripheral lung lesion. In 341 transversely cut cartilaginous airway sections we measured airway size and airway wall dimensions. Inflammatory changes from the same lungs were scored in noncartilaginous airways. Preoperatively measured maximum expiratory flows and the response to a bronchodilator were correlated with airway wall dimensions. Maximum expiratory flow, the reversibility of airflow obstruction, and peripheral airway inflammation were significantly related to the airway wall area but not to the smooth muscle area. We conclude that airflow obstruction and its reversibility in COPD is in part caused by thickening of the cartilaginous airway wall and is related to inflammatory changes.

Airway Resistance↗
PubMed1995

Simple prognostic model to predict survival in patients with undifferentiated carcinoma of unknown primary site.

PURPOSE: We performed this study to identify prognostic factors in a subgroup of patients with carcinoma of unknown primary site treated with cisplatin combination chemotherapy. PATIENTS AND METHODS: Seventy-nine patients with poorly differentiated adenocarcinoma or undifferentiated carcinoma of unknown primary site were treated on two consecutive phase II chemotherapy protocols. The first protocol consisted of treatment with 3-week courses of cisplatin, etoposide, and bleomycin (BEP). In the second protocol, cisplatin was administered weekly combined with oral administration of etoposide (DDP/VP). To identify prognostic factors, univariate and multivariate analyses were conducted. RESULTS: In the univariate analysis, performance status, histology, liver or bone metastases, and serum levels of alkaline phosphatase and AST were significant variables to predict survival. In the multivariate analysis, performance status and alkaline phosphatase were the most important prognostic factors. CONCLUSION: Good-prognosis patients had a performance score of 0 (World Health Organization [WHO]) and an alkaline phosphatase serum level less than 1.25 times the upper limit of normal (N). These patients had a median survival duration greater than 4 years. Intermediate-prognosis patients were characterized by either a WHO performance status < or = 1 or an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of 10 months and a 4-year survival rate of only 15%. The poor-prognosis group had both a WHO performance status > or = 1 and an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of only 4 months and none survived beyond 14 months. Treatment strategies for these three groups are discussed. It is suggested that this prognostic model be validated in other patients series.

Adenocarcinoma↗
PubMed1995

The effect of asphyxia on the pharmacokinetics of ceftazidime in the term newborn.

The multiple-dose pharmacokinetics of ceftazidime (CAZ) (administered twice daily in a 50 mg/kg of body weight i.v. dose) were studied in 10 severely asphyxiated term infants with suspected septicemia on d 3 of life. Nine term infants with suspected septicemia but without asphyxia served as controls. Blood samples were collected from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an i.v. bolus injection. A high performance liquid chromatography method was used to determine CAZ concentrations from serum. CAZ pharmacokinetics followed a one-compartment open model. The GFRs of all infants were simultaneously studied by means of the 24-h continuous inulin infusion technique. Elimination serum half-life (5.86 +/- 1.13 h versus 3.85 +/- 0.40 h) and serum trough concentrations (46 +/- 14 mg/L versus 23 +/- 7 mg/L) of CAZ were significantly (p < 0.001) increased in the asphyxiated newborn, whereas total body clearance of CAZ (128.4 +/- 25.1 mL/h versus 205.7 +/- 55.4 mL/h), CAZ clearance per kg (40.9 +/- 6.1 mL/h/kg versus 60.8 +/- 8.3 mL/h/kg), and the GFR expressed in mL/min (3.14 +/- 0.43 versus 4.73 +/- 0.89) were significantly (p < 0.001) decreased in the asphyxiated newborn. We conclude that twice daily administration of 50 mg/kg of body weight CAZ given to asphyxiated term newborns in the first days of life results in significantly higher serum trough levels in comparison with control infants. The impaired CAZ clearance is a result of a significantly decreased GFR.

Asphyxia Neonatorum↗
PubMed1995

Use of APACHE II classification to evaluate outcome and response to therapy in acute renal failure patients in a surgical intensive care unit.

The study objective was to determine the applicability of the acute physiology and chronic health evaluation (APACHE) II score in surgical patients with acute renal failure (ARF) requiring dialytic support, and to assess its utility in evaluating data from this specific disease group. This was a retrospective, partly prospective follow-up study of patients who developed ARF during their course of stay on the surgical intensive care unit (ICU) of a Dutch university hospital from January 1, 1986, to January 31, 1994. A total of 111 patients were identified, of whom 104 patients were considered eligible for this study. Data for the individual APACHE II scores were calculated from the most deranged values during the initial 24 h of ICU admission (APACHE II1) and on the day dialytic support was instituted (APACHE II2). The ratio between the two APACHE II scores was also calculated for each patient (AP2/AP1 ratio). Receiver operating characteristic curves (ROC) were constructed. Other variables evaluated included age, sex, serum creatinine, diagnostic category, time from ICU admission to start of dialytic support, and the type of dialytic support. Of these 104 patients (median age 64; range 23-85 years), 51 (50%) survived to leave the ICU, of whom 47 (46%) survived to leave hospital. The APACHE II2 score (27.0 +/- 4.4 vs. 22.4 +/- 3.5; p < 0.001) and AP2/AP1 ratio (1.12 +/- 0.09 vs. 0.97 +/- 0.06; p < 0.001) were significantly higher for nonsurvivors as compared to survivors. The ROC curve was most discriminative for the AP2/AP1 ratio (area under the curve 0.92) and to a lesser extent for the APACHE II2 score (area under the curve 0.78). Estimated risk of death with the APACHE II equation did not improve predictive power. Multivariate analysis of various variables revealed the AP2/AP1 ratio as the single most important factor predicting death (odds ratio 13.8, p < 0.001). Adjusting for the AP2/AP1 ratio, no impact on outcome was observed for age, diagnostic category, time from ICU admission to start of dialytic support, and the type of dialytic support. Above a value of 1.0 of the AP2/AP1 ratio, logistic regression revealed a sharp increase in death probability with increasing AP2/AP1 ratio. APACHE II, when used at the time of initiation of dialytic support, proved to be a valid way in our surgical ICU to stratify ARF patients by the severity of their illness. Moreover, use of the AP2/AP1 ratio further improved the usefulness of this severity index and may help to identify patients who have little chance of survival. Predicting death with the APACHE II equation did not improve predictive power.

APACHE↗