Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest.

BACKGROUND: Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA). METHODS: Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university center. Serum levels of GDF-15 were measured on admission. Neurologic status was evaluated according to the cerebral performance category (CPC) scale. The relationship between GDF-15 levels and poor neurologic outcome at 6 months was analyzed. RESULTS: Among 62 patients included, 32 (51.6%) presented poor outcome (CPC 3-5). Patients with CPC 3-5 exhibited significantly higher GDF-15 levels (median, 17.1 [IQR, 11.1-20.4] ng/mL) compared to those with CPC 1-2 (7.6 [IQR, 4.1-13.1] ng/mL; p = 0.004). Multivariable logistic regression analyses showed that age (OR, 1.09; 95% CI 1.01-1.17; p = 0.020), home setting arrest (OR, 8.07; 95% CI 1.61-40.42; p = 0.011), no bystander cardiopulmonary resuscitation (OR, 7.91; 95% CI 1.84-34.01; p = 0.005), and GDF-15 levels (OR, 3.74; 95% CI 1.32-10.60; p = 0.013) were independent predictors of poor outcome. The addition of GDF-15 in a dichotomous manner (≥ 10.8 vs. < 10.8 ng/mL) to the resulting clinical model improved discrimination; it increased the area under the curve from 0.867 to 0.917, and the associated continuous net reclassification improvement was 0.90 (95% CI 0.48-1.44), which allowed reclassification of 37.1% of patients. CONCLUSIONS: After an OHCA, increased GDF-15 levels were an independent, early predictor of poor neurologic outcome. Furthermore, when added to the most common clinical factors, GDF-15 improved discrimination and allowed patient reclassification.

Acute-phase dynamics and prognostic value of growth differentiation factor-15 in ST-elevation myocardial infarction.

Background Growth differentiation factor 15 (GDF-15) in ST-elevation myocardial infarction (STEMI) is prognostic in first-generation radioimmunoassays. We examined GDF-15 temporal dynamics in STEMI and its predictive value using a first fully automated GDF-15 electrochemiluminescence assay. Methods In this prospective study, circulating GDF-15 concentration was measured at admission (0 h), 12 h and 24 h in 1026 consecutive STEMI patients treated between February 2011 and May 2016 with primary percutaneous coronary intervention. GDF-15 dynamics (0 h, 12 h, 24 h) and predictive value (30 days and 3 years) were examined. Results Median GDF-15 concentration was 1443 pg/mL at 0 h, 1731 pg/mL at 12 h and 1510 pg/mL at 24 h (p<0.001). During follow-up, 94 patients died (9.2%) and 154 (15.0%) were hospitalized. GDF-15 was a strong predictor of 30-day mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI], 1.33-2.34 at 0 h; HR 2.99 [95% CI, 2.18-4.09] at 12 h, and HR 1.97 [95% CI, 1.47-2.63] at 24 h) in multivariable Cox proportional hazards models. GDF-15 improved discrimination and reclassification of a clinical risk model. GDF-15 was also associated with 3-year mortality (HR 1.31 [95% CI, 1.04-1.65] at 0 h, HR 1.42 [95% CI, 1.10-1.84] at 12 h, and HR 1.51 [95% CI, 1.16-1.96] at 24 h) and 3-year composite of mortality and cardiovascular hospitalization (HR 1.17 [95% CI, 1.01-1.37] at 0 h, HR 1.20 [95% CI, 1.02-1.42] at 12 h, and HR 1.27 [95% CI, 1.08-1.50] at 24 h). Conclusions GDF-15 peaked at 12 h and remained elevated at 24 h in STEMI. GDF-15 measurement during the first 24 h in STEMI is valuable for predicting especially short- but also long-term outcomes, and may be a useful addition to risk stratification.

Prognostic value of the Stanniocalcin-2/PAPP-A/IGFBP-4 axis in ST-segment elevation myocardial infarction.

OBJECTIVE: The aim of the present study was to evaluate the prognostic value of the Stanniocalcin-2/PAPP-A/IGFBP-4 axis in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Observational cohort study performed in 1085 consecutive STEMI patients treated with early reperfusion between February 2011 and August 2014. Stanniocalcin-2, PAPP-A, and IGFBP-4 were measured using state-of-the art immunoassays. The primary outcome was the composite endpoint of all-cause mortality and readmission due to heart failure (HF). RESULTS: Median follow-up was 3.3 years (IQR 1.0-3.7), during which 176 patients (16.2%) presented a composite endpoint. Multivariable cox regression analysis revealed that Stanniocalcin-2 (HR 2.06; 95% CI 1.13-3.75; p = 0.018), IGFBP-4 (HR 1.73; 95% CI 1.14-2.64; p = 0.010), Killip-Kimball class III-IV (HR 1.40; 95% CI 1.13-1.74; p = 0.002), NT-ProBNP (HR 1.21; 95% CI 1.07-1.37; p = 0.002), age (HR 1.06; 95% CI 1.04-1.08; p < 0.001) and left ventricular ejection fraction (HR 0.97; 95% CI 0.95-0.98; p < 0.001) were independent predictors of the composite endpoint. A model containing Stanniocalcin-2 and IGFBP-4 on top of clinical variables significantly improved C-index discrimination (p = 0.036). Stanniocalcin-2 was also identified as independent predictor of all-cause mortality (HR 2.23; 95% CI 1.16-4.29; p = 0.017) and readmission due to HF (HR 3.42; 95% CI 1.22-9.60; p = 0.020). CONCLUSIONS: In STEMI patients, Stanniocalcin-2 and IGFBP-4 emerged as independent predictors of all-cause death and readmission due to HF. The Stanniocalcin-2/PAPP-A/IGFBP-4 axis exhibits a significant role in STEMI risk stratification.

Stroop Color-Word Interference Test: Normative data for Spanish-speaking pediatric population.

OBJECTIVE: To generate normative data for the Stroop Word-Color Interference test in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the Stroop Word-Color Interference test as part of a larger neuropsychological battery. The Stroop Word, Stroop Color, Stroop Word-Color, and Stroop Interference scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on all scores, except on Stroop Interference for Guatemala, such that scores increased linearly as a function of age. Age2 affected Stroop Word scores for all countries, Stroop Color scores for Ecuador, Mexico, Peru, and Spain; Stroop Word-Color scores for Ecuador, Mexico, and Paraguay; and Stroop Interference scores for Cuba, Guatemala, and Spain. MLPE affected Stroop Word scores for Chile, Mexico, and Puerto Rico; Stroop Color scores for Mexico, Puerto Rico, and Spain; Stroop Word-Color scores for Ecuador, Guatemala, Mexico, Puerto Rico and Spain; and Stroop-Interference scores for Ecuador, Mexico, and Spain. Sex affected Stroop Word scores for Spain, Stroop Color scores for Mexico, and Stroop Interference for Honduras. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the Stroop Word-Color Interference test in pediatric populations.

Rey-Osterrieth Complex Figure - copy and immediate recall (3 minutes): Normative data for Spanish-speaking pediatric populations.

OBJECTIVE: To generate normative data for the Rey-Osterrieth Complex Figure (ROCF) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the ROCF as part of a larger neuropsychological battery. The ROCF copy and immediate recall (3 minutes) scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effect for age on copy and immediate recall scores, such that scores increased linearly as a function of age. Age2 affected ROCF copy score for all countries, except Puerto Rico; and ROCF immediate recall scores for all countries, except Chile, Guatemala, Honduras, Paraguay, and Puerto Rico. Models indicated that children whose parent(s) had a MLPE >12 years obtained higher scores compared to children whose parent(s) had a MLPE≤12 years for Chile, Puerto Rico, and Spain in the ROCF copy, and Paraguay and Spain for the ROCF immediate recall. Sex affected ROCF copy and immediate recall score for Chile and Puerto Rico with girls scoring higher than boys. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the ROCF Test in pediatric populations.

Contaminación de antígeno específico-prostático a largo plazo en la rama española del Estudio Aleatorizado Europeo de Screeningdel Cáncer de Próstata (ERSPC) / Long-term prostate-specific antigen contamination in the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC)

Objetivos: Recientemente, el Estudio Aleatorizado Europeo de Screening del Cáncer de Próstata consiguió una reducción de la mortalidad por cáncer de próstata mediante la determinación sérica de antígeno específico-prostático (PSA). Estos resultados no fueron reproducidos en la rama española del Estudio Aleatorizado Europeo de Screening del Cáncer de Próstata. La contaminación de PSA (determinación oportunista fuera del estudio) podría disminuir el poder de contraste del estudio si se lleva a cabo en el brazo control. Hemos calculado la tasa de contaminación de PSA a largo plazo, y su efecto en la realización de biopsia prostática y en la detección de cáncer. Material y métodos: Se aleatorizaron 4.276 varones (2.415 brazo screening, 1.861 brazo control) en la sección española del Estudio Aleatorizado Europeo de Screening del Cáncer de Próstata. No se programó la determinación de PSA en el brazo control. Se indicó biopsia prostática sextante si PSA ≥ 3 ng/ml. Toda determinación de PSA realizada fuera del estudio fue etiquetada como «contaminación de PSA». Se calcularon las tasas de contaminación de PSA, realización de biopsia y detección de cáncer. Resultados: Las medianas de edad y tiempo de seguimiento fueron de 57 y 15,1 años respectivamente. Un total de 2.511 varones se realizó al menos una determinación de PSA fuera del estudio. La contaminación de PSA a los 5, 10 y 15 años fue del 22; 47,1 y 66,3% en el brazo screening, y del 20,8; 43,2 y 58,6 en el brazo control, respectivamente (p < 0,0001). La tasa de biopsia a los 5, 10 y 15 años fue del 19,3; 22,6 y 24,1% (screening) y del 1; 3,6 y 7,1% (control), respectivamente (p < 0,0001). La detección de cáncer de próstata fue del 6,7% (screening) y del 4,3% (control, p = 0,0006). Conclusiones: Aunque la contaminación acumulada de PSA fue notable en los 2 brazos del estudio, la realización de biopsia prostática fue escasa en el brazo control. Por ello, creemos que el impacto de la contaminación de PSA sobre el poder estadístico del estudio debe ser limitado

Objectives: Recently, the European Randomized Study of Screening for Prostate Cancer achieved a reduction in prostate cancer mortality by measuring serum prostate-specific antigen (PSA) levels. These results were not reproduced in the Spanish arm of European Randomized Study of Screening for Prostate Cancer. PSA contamination (opportunistic measurements outside the study) could decrease the study's contrasting power if performed in the control arm. We have calculated the long-term rate of PSA contamination and its effect on performing prostate biopsy and detecting cancer. Material and methods: A total of 4,276 men were randomised (2,415 to the screening arm, 1,861 to the control arm) in the Spanish section of the European Randomized Study of Screening for Prostate Cancer. PSA measurements were not scheduled in the control arm. Sextant prostate biopsy was indicated if PSA levels were ≥ 3 ng/mL. All PSA readings performed outside the study were labelled as "PSA contamination". We calculated the rates of PSA contamination, biopsy implementation and cancer detection. Results: The median age and follow-up time were 57 and 15.1 years, respectively. A total of 2,511 men underwent at least one PSA reading outside the study. PSA contamination at 5, 10 and 15 years was 22.0%, 47.1% and 66.3% in the screening arm, respectively, and 20.8%, 43.2% and 58.6% in the control arm, respectively (P < .0001). The biopsy rate at 5, 10 and 15 years was 19.3%, 22.6% and 24.1% (screening), respectively, and 1.0%, 3.6% and 7.1% (control), respectively (P < .0001). The PC detection rate was 6.7% (screening) and 4.3% (control; P = .0006). Conclusions: Although the cumulative PSA contamination was pronounced in the 2 study arms, the rate of prostate biopsies was low in the control arm. We therefore believe that the effect of PSA contamination on the study's statistical power should be limited

Long-term prostate-specific antigen contamination in the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

OBJECTIVES: Recently, the European Randomized Study of Screening for Prostate Cancer achieved a reduction in prostate cancer mortality by measuring serum prostate-specific antigen (PSA) levels. These results were not reproduced in the Spanish arm of European Randomized Study of Screening for Prostate Cancer. PSA contamination (opportunistic measurements outside the study) could decrease the study's contrasting power if performed in the control arm. We have calculated the long-term rate of PSA contamination and its effect on performing prostate biopsy and detecting cancer. MATERIAL AND METHODS: A total of 4,276 men were randomised (2,415 to the screening arm, 1,861 to the control arm) in the Spanish section of the European Randomized Study of Screening for Prostate Cancer. PSA measurements were not scheduled in the control arm. Sextant prostate biopsy was indicated if PSA levels were ≥3 ng/mL. All PSA readings performed outside the study were labelled as "PSA contamination". We calculated the rates of PSA contamination, biopsy implementation and cancer detection. RESULTS: The median age and follow-up time were 57 and 15.1 years, respectively. A total of 2,511 men underwent at least one PSA reading outside the study. PSA contamination at 5, 10 and 15 years was 22.0%, 47.1% and 66.3% in the screening arm, respectively, and 20.8%, 43.2% and 58.6% in the control arm, respectively (P<.0001). The biopsy rate at 5, 10 and 15 years was 19.3%, 22.6% and 24.1% (screening), respectively, and 1.0%, 3.6% and 7.1% (control), respectively (P<.0001). The PC detection rate was 6.7% (screening) and 4.3% (control; P=.0006). CONCLUSIONS: Although the cumulative PSA contamination was pronounced in the 2 study arms, the rate of prostate biopsies was low in the control arm. We therefore believe that the effect of PSA contamination on the study's statistical power should be limited.

Prostate cancer incidence and mortality in the Spanish section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

BACKGROUND: To present the long-term results of a prostate cancer (PC) screening trial conducted in a Mediterranean setting. METHODS: A total of 4276 men aged 45-70 years were randomized to screening arm (PSA test performed) and control arm (no tests). Transrectal ultrasonography-guided sextant prostate biopsy was conducted when PSA > or = 3 ng ml(-1). Date and cause of death were retrieved from death certificates. PC incidence, and disease-specific and overall mortality curves were plotted and comparison between arms was made. Analysis of causes of death was also performed. RESULTS: Median age at randomization was 57.0 years. Median follow-up time was 15.2 years. A total of 241 men were diagnosed with PC, 161 (6.7%) in the screening arm and 80 (4.3%) in the control arm (P<0.01). Eventually, 554 men (13%) died. No difference in all-cause mortality was found between arms (P=0.34). Only 10 men (10/4276, 0.23%) died from PC, no differences between arms (P=0.67). Overall, the main causes of death were malignancy (54.2%), cardiovascular (17.9%) and respiratory (9.2%) diseases. Main cancer causes of death were lung and bronchus cancer (37.2%), colorectum (15.0%) and stomach (9.0%) cancer. PC only accounted for 3.0% of all malignant causes of death (ranked 10th). CONCLUSIONS: Our study failed to demonstrate benefits of PC screening in terms of all-cause and PC-specific mortality after a median follow-up of 15 years. The limited sample size and the low long-term PC mortality observed in our setting were probably the most important factors to explain these results.

[Retrorectal cystic hamartoma (tailgut cyst): radiologic and pathologic findings]. / Hamartoma quístico retrorrectal: hallazgos radiopatológicos.

Cystic hamartoma is a rare congenital lesion that presents as a presacral mass. It arises from remnants of the embryonic postanal gut. It is more common in women and usually presents in middle age. It is usually asymptomatic. It is difficult to distinguish the imaging appearance of cystic hamartoma from that of many other presacral cysts; therefore, histologic analysis is essential for the definitive diagnosis. Complete surgical excision is indicated to establish the diagnosis and avoid complications (infection and malignant transformation).

Hamartoma quístico retrorrectal: hallazgos radiopatológicos / Retrorectal cystic hamartoma (tailgut cyst): Radiologic and pathologic findings

El hamartoma quístico retrorrectal es una rara lesión congénita que suele presentarse como una masa presacra. Se origina a partir de restos del intestino caudal embrionario. Es más frecuente en mujeres y generalmente se diagnostica en la edad media. Suele ser asintomático. Radiológicamente puede ser indistinguible de otras lesiones quísticas que también pueden presentarse en la región presacra, por lo que el examen histológico de la pieza resulta imprescindible para su diagnóstico definitivo. El tratamiento quirúrgico es fundamental para establecer el diagnóstico y para evitar complicaciones (infección y degeneración maligna) (AU)

Cystic hamartoma is a rare congenital lesion that presents as a presacral mass. It arises from remnants of the embryonic postanal gut. It is more common in women and usually presents in middle age. It is usually asymptomatic. It is difficult to distinguish the imaging appearance of cystic hamartoma from that of many other presacral cysts; therefore, histologic analysis is essential for the definitive diagnosis. Complete surgical excision is indicated to establish the diagnosis and avoid complications (infection and malignant transformation) (AU)

Malignant melanomas of the nasolacrimal duct.

Two patients with a history of epistaxis who were both found to have a nasolacrimal duct melanoma are presented. A literature review revealed that no previous cases of primary nasolacrimal duct melanoma have been reported. Current therapeutic modalities are discussed.

Long-term reversal of hypocholesterolaemia in patients with chronic hepatitis C is related to sustained viral response and viral genotype.

BACKGROUND: Genotype-3 of hepatitis C virus (HCV) has been associated with serum lipid changes (reversible with sustained viral response) and liver steatosis. AIM: To characterize the relationships among hepatic steatosis, cholesterol and sustained viral response in these patients. METHODS: Patients (n = 215) with chronic hepatitis C (157 with genotype-1 of HCV) had age, body mass index, gender, alcohol intake, glycaemia, serum lipids, transaminases, grade and stage (METAVIR and Scheuer), degree of liver steatosis, sustained viral response, insulinaemia, leptinaemia, beta-hydroxybutyrate and glycerol measured, and were compared with 32 hepatitis B virus (HBV)-infected subjects. RESULTS: Genotype-3 of HCV patients had age-adjusted hypocholesterolaemia and more frequent hepatic steatosis (P < 0.001). Steatosis was inversely correlated with serum cholesterol (P < 0.01) and directly with viral load (P < 0.03). In patients with genotype-3 of HCV and sustained viral response, serum cholesterol increased from 138 (95% CI: 120-151) to 180 mg/dL (95% CI: 171-199) 12 months after treatment conclusion (P < 0.0001). By contrast, cholesterol values were unchanged in genotype-3 of HCV non-responders and in patients with genotype-1 of HCV regardless of response. Rising cholesterol in sustained viral response did not parallel the changes in beta-hydroxybutyrate. CONCLUSIONS: Besides causing hepatic steatosis, genotype-3 specifically decreases serum cholesterol. This interference with the metabolic lipid pathway is related to viral load, is reversed with sustained viral response, and seems unrelated to mitochondrial dysfunction.

Síndrome metabólico y progresión de la lesión hepática en la infección por el virus de la hepatitis C y el hígado graso no alcohólico / No disponible

No disponible

Collagenous gastrobulbitis and collagenous colitis. Case report and review of the literature.

A case is reported of collagenous gastrobulbitis on collagenous colitis in a 57-year-old woman with a 6-month history of watery diarrhea. Low serum levels of total proteins and albumin and increased fecal elimination of alpha1-antitrypsin were the only abnormal laboratory test results. Biopsy specimens from the colon, rectum, antrum, fundus, and duodenal bulb showed a thick subepithelial band composed of ultrastructurally normal collagen immunohistochemically negative for collagen IV and laminin. The diarrhea resolved with prednisone and responded to this treatment after a relapse 6 months later. One year later the patient developed severe alimentary intolerance and secondary weight loss. This symptom also responded to the same treatment. However, the collagen deposition did not disappear in the second biopsy samples of colonic and gastric mucosa. Only six cases have been previously reported with gastric and/or duodenal subepithelial collagenous deposition. Four were associated with collagenous colitis. One of these presented a subepithelial collagenous band in the terminal ileum. All these features suggest that this collagen deposition may affect the entire digestive tract with variable intensity, extension, and symptoms.

Immunological detection and quantification of oxidized proteins by labelling with digoxigenin.

An immunological assay, based on the digoxigenin/anti-digoxigenin system, was developed to detect and quantify carbonyl moieties that result from oxidative damage to proteins. Bovine serum albumin (BSA) was oxidized by a hydroxyl radical-generating system consisting of ascorbate/Fe(III)/O2. The resulting albumin-derived carbonyls were labelled with digoxigenin-hydrazide and detected by dot blotting with an anti-digoxigenin antibody conjugated to alkaline phosphatase. Quantification was carried out by a densitometric analysis. This system allows the detection of a pmole-amount of carbonyl groups on blots. The assay covers a range of sensitivity from 1.26 to 126 pmoles. Another feature of this method is its application to a complex protein mixture (homogenate) to analyze the oxidative status of individual proteins, as are shown for intestinal brush border membrane homogenate of a rat.

Fine needle aspiration diagnosis of carcinoma arising in an ectopic breast. A case report.

BACKGROUND: Ectopic breast tissue has been found at many anatomic locations. Neoplastic and hyperplastic lesions similar to those that develop in the normal breast can occur in supernumerary ones. CASE: A 45-year-old female presented with a 30-cm, firm, subcutaneous mass in the left side of the chest wall that was clinically considered an ectopic breast. Fine needle aspiration biopsy showed irregular clusters and single epithelial cells with marked atypia, pleomorphism and occasional magenta bodies. CONCLUSION: This case illustrates that fine needle aspiration biopsy is a rapid and highly specific technique that can be used as the first diagnostic step in cases of carcinoma arising in an ectopic breast.

Histological diagnosis of cytomegalovirus hepatitis in liver allografts.

AIMS--To determine the incidence of histologically documented cytomegalovirus (CMV) hepatitis following orthotopic liver transplantation (OLT) and to assess the effectiveness of immunohistochemistry and in situ hybridisation (ISH) in detecting CMV. To describe the histological pattern most frequently associated with CMV hepatitis in order to select the biopsy group in which these modern techniques are most effective. METHODS--A prospective histological study was carried out on 853 biopsy specimens, obtained from 191 liver allografts (160 patients). Specimens were stained with haematoxylin and eosin and immunohistochemically (avidin-biotin complex) using monoclonal antibodies directed against early and late CMV antigens. A retrospective selection was made of 23 specimens with viral inclusion bodies in cytomegalic cells (group A) to characterise the most frequently associated histological pattern, and of 34 other specimens without viral inclusion bodies (group B) but with the same microscopic features as group A. Re-cuts from both specimen groups were studied using immunohistochemistry and ISH with a CMV specific complementary DNA probe. RESULTS--CMV infection was confirmed in 35 specimens (29 by immunohistochemistry, 23 by presence of inclusion bodies in haematoxylin and eosin stained sections, 16 by ISH) from 27 patients (incidence 16.9%). CMV hepatitis was diagnosed within 46 +/- 19 (range 21-114) days posttransplant. Twenty on (91.3%) of the 23 biopsy specimens with inclusion bodies (group A) displayed heterogeneous inflammatory foci disseminated throughout the hepatic lobule. Nineteen specimens (82.6%) were positive by immunohistochemistry and 14 (60.9%) by ISH. In eight (23.5%) of the 34 group B specimens CMV infection was confirmed by immunohistochemistry (n = 6) or ISH (n = 2). Another 12 (35.3%) of the group B specimens negative on staining with haematoxylin and eosin, immunohistochemistry and ISH came from allografts in which previous or subsequent biopsy specimens were CMV positive. CONCLUSIONS--Demonstration of cytomegalic inclusion bodies in haematoxylin and eosin sections is sufficient for a diagnosis of CMV hepatitis. The routine use of immunohistochemistry in all allograft biopsy specimens in more sensitive than demonstration of inclusion bodies by staining with haematoxylin and eosin but may yield false negative results because of the focal distribution of positive cells. ISH was less sensitive than staining with haematoxylin and eosin and/or immunohistochemistry. A histological picture of "disseminated focal hepatitis" without viral inclusion bodies selects a group of allograft biopsy specimens in which immunohistochemistry and/or ISH may improve detection of CMV.

Synthesis of 21-hydroxy-11,19-oxidopregn-4-ene-3,20-dione and 21-hydroxy-6,19-oxidopregn-4-ene-3,20-dione.

The 21-hydroxy analogues of 11,19-oxidoprogesterone and 6,19-oxidoprogesterone have been synthesized from readily available materials. Hydroxylation at C-21 was effected with iodosobenzene (from phenyliodosodiacetate and methanolic potassium hydroxide) on a 20-ketopregnane. For the 11,19-oxido derivative, the hydroxylation was carried out on a precursor containing the oxido-bridge. This approach was not adequate for the 6,19-oxido steroid due to the very low yields encountered; hence in the latter case the order of introduction of the C-21 functionality and the oxido-bridge was reversed.