Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.

BACKGROUND: We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. METHODS: Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. RESULTS: Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens. CONCLUSION: Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.

Recombinant streptokinase suppositories in the treatment of acute haemorrhoidal disease. Multicentre randomized double-blind placebo-controlled trial (THERESA-2).

AIM: A four-arm multicentre randomized double-blind placebo-controlled trial was undertaken to assess the effect and safety of suppositories containing recombinant streptokinase (rSK) at two dose levels (100,000 IU and 200,000 IU) with sodium salicylate (SS) compared with placebo and SS for the treatment of acute haemorrhoidal disease. METHOD: Patients with acute symptoms of haemorrhoids were randomized to four treatment groups: (I) placebo, (II) SS, (III) SS + rSK 100,000 IU and (IV) SS + rSK 200,000 IU per suppository. Inpatient treatment was by four suppositories given every 6 h to discharge at 24 h. Evaluations were made at the time of discharge (24 h) and at 3, 5 and 20 days later. The main end-point was the degree of relief of pain, oedema and reduction in the size of the lesion by 90% on day 5. Adverse events and the occurrence of anti-SK antibodies were also determined. RESULTS: Eighty patients were included. Respective response rates in the four groups were 16%, 30%, 25% and 52%. In the last group there was a significant difference (36.8%) compared with control (95% CI 7.0-58.4%). The time to response was significantly shorter (median 5 days) in the 200,000 IU rSK group with respect to the others. There were no adverse events attributable to the treatment. No increase in anti-SK antibodies was detected 20 days after treatment. CONCLUSION: Suppositories with 200,000 IU rSK showed a significant improvement in symptoms of acute haemorrhoids, with an adequate safety profile.

[Prognosis of patients with COVID-19 presenting acute ischaemic stroke and receiving interventional treatment]. / Pronóstico de pacientes COVID-19 con ictus isquémico y tratamiento neurointervencionista.

Objetivo: Presentar nuestra experiencia y analizar el pronóstico de pacientes COVID-19 con ictus isquémico agudo por oclusión de grandes vasos tratados con neurointervencionismo (NIV) en la unidad de ictus. Material y métodos: Se incluyeron todos los pacientes consecutivos con ictus isquémico agudo debido a oclusión de grandes vasos tratados por NIV en nuestra institución entre marzo y abril de 2020, durante el brote de COVID-19. Se realizó una comparación entre pacientes con COVID-19 y pacientes sin infección por coronavirus. Se comunican los resultados clínicos iniciales y a corto plazo. Resultados: Del 1 de marzo al 30 de abril se realizaron 25 procedimientos de NIV por ictus isquémico agudo en nuestra institución. Ocho pacientes eran COVID-19 y 17 eran pacientes no COVID-19. La edad media de los pacientes con COVID-19 fue de 70,1 ± 12,23 años, y 7 fueron hombres (87,5%, p = 0,006). Mientras que todos los pacientes sin COVID procedían de urgencias, solo 5 pacientes con COVID-19 (62,5%) fueron atendidos desde urgencias por ictus (p = 0,01). Tres pacientes procedían de hospitalización. La tasa de mortalidad en pacientes sin COVID-19 fue del 5,8%, pero en pacientes con COVID-19 fue considerablemente alta (50%). Ningún parámetro analítico difirió entre ambos grupos. No se registraron hemorragias en esta serie.En comparación con el mismo período del año pasado, se observó una disminución de la actividad neurointervencionista del 39%. Conclusiones: La mejor terapia médica y de NIV desembocó en malos resultados y una mortalidad dramática. La pandemia de COVID-19 dificultó significativamente el funcionamiento normal de los servicios de urgencias y la atención de estos pacientes con ictus.

Treatment with type I interferons induces a regulatory T cell subset in peripheral blood mononuclear cells from multiple sclerosis patients.

Type I Interferon (IFN-alpha/beta) therapy has altered the natural course of multiple sclerosis. In this paper we evaluate the possible molecular mechanisms involved in the in vitro effects of IFN-alpha/beta on peripheral blood mononuclear cells from patients with clinically definite Relapsing-Remitting Multiple Sclerosis. The total RNA from IFN-alpha, IFN-beta treated cells and untreated cells was extracted and amplified for CD86, CD28, CTLA-4, TNF-alpha, IFN-gamma, CCL2, CCR5, IL-13, MMP-9, TIMP-1, CD25, TGF-beta, IL-10 and the transcriptional factor Foxp3 by Reverse Transcription-Polymerase Chain Reaction and the CD4+CD25high subset was evaluated using flow cytometry. In general, there were no significant differences concerning the modulation of the genes studied in the response to IFN-alpha and IFN-beta treatments, which suggest a similar mechanism of action for both interferons. However, we found a significant increment in IFN-gamma expression after IFN-alpha but not after IFN-beta treatments. The in vitro treatment of mononuclear cells from multiple sclerosis patients with both interferons significantly increased the CD25 mRNA. Furthermore, we observed a CD25/Foxp3 correlation and an increment of the CD4+CD25high subset, indicating that the induction of regulatory T cells could be a crucial mechanism involved in the type I interferon effects.

Endovascular treatment of intracranial aneurysms using the Pipeline Flex embolization device: a case series of 30 consecutive patients.

BACKGROUND: The Pipeline Flex embolization device has some peculiarities in comparison with the previous generation device. Despite recent reports of the modified delivery system, its safety is still unknown. OBJECTIVE: To illustrate the intraprocedural and periprocedural complication rate with this new device in 30 consecutive patients. MATERIAL AND METHODS: Clinical, procedural, and angiographic data, including aneurysm size and location, device or devices used, angiographic and clinical data were analyzed. RESULTS: 30 patients harboring 30 aneurysms were analyzed. 39 devices were placed properly. Multiple Pipeline embolization devices (PEDs) were used in 7 cases. In 28 devices the distal end opened fully from the beginning with a complete wall apposition. In the remaining 11 devices, distal-end opening of the devices was instant but partial, but fully opened easily after recapture. Among the 30 procedures, recapture and reposition of the Pipeline Flex was performed four times owing to proximal migration/malposition of the device during delivery. Four intraprocedural/periprocedural complications occurred, of which 2 resulted in major complications, with neurologic deficits persisting for longer than 7 days. The 30-day morbidity rate was 6.6%, with no deaths. No aneurysm rupture or parenchymal hemorrhage was seen. CONCLUSIONS: The Pipeline Flex embolization device allows more precise and controlled deployment than the first-generation device. The number of devices and the complication rate during the learning curve are lower than reported with the first-generation PED. The new delivery system and the resheathing maneuvers do not seem to increase the intraprocedural complication rate in comparison with the first-generation PED.

Analytical fractionation of cultured hepatoma cells (HTC cells).

Homogenates of HTC cells have been fractionated by differential centrifugation (in four particulate fractions: N, M, L, P, and a supernatant S) or isopycnic banding in linear sucrose gradients. On this basis, the following subcellular organelles may be characterized: (i) Mitochondria, detected by cytochrome oxidase and succinodehydrogenase, are collected in the M and L fractions, and equilibrate, as a narrow band, at a median buoyant density of 1.18 g/cm3. (ii) Lysosomes, detected by the latent hydrolases beta-glycerophosphatase and N-acetyl-beta-glucosaminidase, are largely sedimented in the M and L fractions, and display a broad density distribution pattern with a median value of 1.17 g/cm3. This density is decreased or increased after cultivation of the cells in presence of Triton WR-1339 or Dextran 500, respectively. The behavior of cathepsin D is somewhat at variance with that of the two other hydrolases. (iii) Plasma membrane is tentatively detected by alkaline phosphodiesterase I. Largely recovered in the P fraction, this enzyme equilibrates at a median density close to that of the lysosomal hydrolases; the bulk of cholesterol and about half of the leucyl-2-naphthylamidase are closely associated with alkaline phosphodiesterase I; HTC cells do not contain typical 5'-nucleotidase. (iv) Catalase-bearing particles, of high buoyant density (1.22 g/cm3) are present, but 30-40% of the catalase is also found readily soluble. NADPH- and NADH: cytochrome c reductase, and RNA show more complex distributions. It is suggested that the former enzyme is associated with the endoplasmic reticulum; as in liver, NADH reductase activity is shared between the endoplasmic reticulum and the mitochondria; half of the RNA is associated with free ribosomes of polysomes. True glucose-6-phosphatase could not be detected.

Analytical characterization and purification of plasma membrane from cultured hepatoma cells (HTC cells).

The plasma membrane of the hepatoma cell line, HTC cells, has been characterized and purified by cell fractionation techniques. In the absence of true 5'-nucleotidase in HTC cells, alkaline phosphodiesterase I has been used as a marker enzyme, following conclusions gained from differential and isopycnic centrifugation studies (Lopez-Saura, P., Trouet, A. and Tulkens, P. (1978) Biochim. Biophys. Acta 543, 430-449). To confirm this localization, HTC cells were exposed to anti-plasma membrane IgG at 4 degrees C and fractionated. Alkaline phosphodiesterase I and IgG showed superimposable distribution patterns in linear sucrose gradients. Alkaline phosphodiesterase I is, however, only poorly resolved from enzyme markers of other organelles, especially NADPH-cytochrome c reductase (endoplasmic reticulum) and galactosyltransferase (Golgi complex). Maximal purification from the homogenate is only 13-fold, on a protein basis, even when using a microsomal fraction (67 and 13% of alkaline phosphodiesterase I and protein, respectively) as the starting material. Improved resolution can be obtained after the addition of small quantities of digitonin (equimolar with respect to the cholesterol content). Digitonin increases the buoyant density of alkaline phosphodiesterase I by approx. 0.05 g/cm3, whereas the buoyant densities of galactosyltransferase and NADPH-cytochrome c reductase are increased only by 0.03 and 0.015 g/cm3, respectively. Accordingly, a procedure has been designed which yields a fraction containing 22.8% of alkaline phosphodiesterase I with a purification of 21-fold on a protein basis. The content of NADPH-cytochrome c reductase and galactosyltransferase is 1.2 and 2.1%, respectively. Electron microscopy shows smooth surface membrane elements and vesicles, with only occasional other recognizable elements.

Multicenter study of the multiple organ dysfunction syndrome in intensive care units: the usefulness of Sequential Organ Failure Assessment scores in decision making.

OBJECTIVE: This study examined the incidence and mortality of multiple organ dysfunction syndrome (MODS) in intensive care units, evaluated the limitation of life support in these patients, and determined whether daily measurement of the Sequential Organ Failure Assessment (SOFA) is useful for decision making. DESIGN AND SETTING: Prospective, observational study in 79 intensive care units. PATIENTS AND PARTICIPANTS: Of the 7,615 patients admitted during a 2-month period we found 1,340 patients to have MODS. MEASUREMENTS AND RESULTS: We recorded mortality and length of stay in the intensive care unit and the hospital and the maximum and minimum total SOFA scores during MODS. Limitation of life support in MODS patients was also evaluated. Stepwise logistic regression was used to determine the factors predicting mortality. The in-hospital mortality rate in patients with MODS was 44.6%, and some type of limitation of life support was applied in 70.6% of the patients who died. The predictive model maximizing specificity included the following variables: maximum SOFA score, minimum SOFA score, trend of the SOFA for 5 consecutive days, and age over 60 years. The model diagnostic yield was: specificity 100%, sensitivity 7.2%, positive predictive value 100%, and negative predictive value 57.3%; the area under the receiver operating characteristic curve was 0.807. CONCLUSIONS: This model showed that in our population with MODS those older than 60 years and with SOFA score higher than 9 for at least 5 days were unlikely to survive.

Regression of infancy hemangiomas with recombinant IFN-alpha 2b.

Interferon-alpha (IFN-alpha) has antitumor and antiangiogenic effects. The purpose of this work was to evaluate its efficacy and safety in the treatment of infancy hemangioma and to monitor the appearance of anti-IFN antibodies in these patients. Thirty-nine children (29 girls) aged 1.5-158 months, with 19 younger than 1 year and 9 older than 5, were treated with 3 x 10(6) IU/m(2) IFN-alpha 2b, subcutaneously (s.c.) daily. Inclusion criteria were life-threatening or life-limiting hemangioma and parents' informed consent. Regression was considered if tumor size diminished by 50% or more. Of the 38 patients who completed 6 months of treatment, 27 (71.1%) had regression and 11 (28.9%) had stable disease. No patient experienced progression. Regression was more frequent (100%) among patients between 1 and 5 years old, but it was particularly important (68%) among those under 1 year old, when spontaneous regression is rare. The main side effects were the IFN-related flulike syndrome (79%), increase in serum alanine aminotransferase (ALT) (28%), anorexia (19%), and mild inflammation at the injection site (19%). There was no effect on psychomotor or physical development. On the contrary, 1 patient with neurologic symptoms improved remarkably, including seizure disappearance. Eight patients developed anti-IFN-alpha 2 neutralizing antibodies, and 7 of them responded to IFN treatment. IFN-alpha 2b is a safe and efficacious treatment of infancy hemangioma. Further work should look for other treatment schedules and ways of administration and carefully monitor anti-IFN neutralizing antibodies, which does not seem to interfere with response.

Relationship between expired capnogram and respiratory system resistance in critically ill patients during total ventilatory support.

To examine the relationship of expired capnograms and respiratory system resistance (Rrs) in intubated critically ill patients, we consecutively studied 41 mechanically ventilated patients to (1) analyze the association between expired CO2 slope and auto-positive end-expiratory pressure (auto-PEEP), between Rrs and auto-PEEP, between Rrs and expired CO2 slope, and between Rrs and arterial minus end-tidal PCO2 gradient (PaCO2-PETCO2 gradient) and (2) to investigate the capacity of the expired CO2 slope and PaCO2-PETCO2 gradient to predict Rrs during mechanical ventilation. Regression analysis found a close correlation between Rrs and expired CO2 slope (r = 0.86; p < 0.001), between Rrs and auto-PEEP (r = 0.75; p < 0.001), and between auto-PEEP and expired CO2 slope (r = 0.74; p < 0.001). Weak correlation was found between Rrs and PaCO2-PETCO2 gradient (r = 0.48; p < 0.01). Prediction interval limits at 95 percent confidence level for Rrs are approximately +/- 7.39 cm H2O/L/s from the predicted value obtained by the regression equation, where Rrs = 11.42 + 2.28 expired CO2 slope. These observations suggest that CO2 elimination in critically ill patients is strongly modulated by lung, airway, endotracheal tube, and ventilator equipment resistances. Although continuous capnogram waveform monitoring at the bedside might be useful to assess Rrs, very accurate predictions could be done only in determinate patients.

Effect of sucralfate on gastric intramucosal pH in critically ill patients.

OBJECTIVE: To determine whether sucralfate administration affects the tonometric measurement of gastric intramucosal pH (pHi). DESIGN: Non-randomized observational study. SETTING: General intensive care unit of a teaching hospital. PATIENTS: Twenty critically ill, mechanically ventilated, consecutively admitted patients requiring an arterial catheter and nasogastric tube. INTERVENTIONS: Tonometer placement and sucralfate administration. MEASUREMENTS AND MAIN RESULTS: We simultaneously determined tonometer saline PCO2 (PCO2i), arterial blood gases, pH of gastric juice and pHi. These parameters were evaluated immediately before sucralfate administration, and 2 h and 4 h after. We did not detect any change in either PCO2i or pHi after sucralfate administration (PCO2i: basal 6.4 +/- 1.7, 2 h 6.3 +/- 1.7, 4 h 6.3 +/- 1.7; pHi: basal 7.35 +/- 0.13, 2 h 7.36 +/- 0.12, 4 h 7.36 +/- 0.12). CONCLUSIONS: Sucralfate does not affect the tonometric measurement of PCO2i and pHi.

Use of capnography to detect hypercapnic episodes during weaning from mechanical ventilation.

OBJECTIVE: To evaluate the relationship between PaCO2 and end-tidal CO2 tension (PetCO2) before weaning and during a weaning trial and to determine the ability of PetCO2 to identify clinically relevant episodes of hypercapnia. DESIGN: Open, prospective study. SETTING: General intensive care unit. PATIENTS: 30 critically ill patients (mean age 63 +/- 2 years; Acute Physiology And Chronic Health Evaluation (APACHE) II of 18.4 +/- 3) who underwent a weaning trial during the recovery phase of acute respiratory failure requiring mechanical ventilation (MV) (8.9 +/- 1 days on MV). INTERVENTIONS: Weaning trial consisted of 2 h breathing on 5 cmH2O of Continuous Positive Airway Pressure (CPAP). MEASUREMENTS AND RESULTS: Arterial blood gas values, PetCO2 register and pulse oximetry determinations were recorded in assist/control ventilation before CPAP, after 1 h on CPAP and after 2 h on CPAP (immediately before extubation) or immediately before returning to assist/control mode in patients who failed the weaning trial. Clinically relevant hypercapnic episodes were described as: (1) an increment in PaCO2 > 42 mm Hg in previously normocapnic patients and (2) an increment of > 8 mm Hg from previous PaCO2 in previously hypercapnic patients. Changes in PaCO2 and changes in PetCO2 between MV and the first and second hour of CPAP showed a significant correlation (r = 0.74; p < 0.01). Clinically relevant hypercapnic episodes were detected by increments of > 3 mm Hg in PetCO2 with a sensitivity of 82%, a specificity of 76% and a negative predictive value of 94%. The area under the receiver operating characteristic curve for increments in PetCO2 was 0.90. CONCLUSIONS: Capnography provided good assessment of hypercapnic episodes during weaning, although the high number of false positives may result in arterial blood sampling in patients who do not present with ventilation failure.

Clinical consequences of the implementation of a weaning protocol.

OBJECTIVE: To analyze the clinical and economic consequences of the implementation of a weaning protocol in patients mechanically ventilated (MV) for more than 48 h. DESIGN: Comparative study. SETTING: General intensive care unit (ICU) in a county hospital covering 360000 inhabitants. PATIENTS: 51 patients weaned by a fixed protocol were studied prospectively and compared with 50 retrospective controls. MEASUREMENTS: The following variables were assessed: Acute Physiology and Chronic Health Evaluation (APACHE) II score, age, cause of respiratory failure, type of extubation (direct extubation or extubation using a weaning technique), number of days on MV before the weaning trial, weaning time, total duration of MV, complications (reintubations and tracheostomies), length of ICU stay, and mortality. RESULTS: The groups were comparable in terms of age, APACHE II score, and main cause of acute respiratory failure. Number of days on MV up to the weaning trial were similar in the two groups (8.4 +/- 7.7 in the protocol group vs 7.5 +/- 5.5 in the control group, NS). Most of the patients (80%) in the protocol group were directly extubated without a weaning technique, unlike the control group (10%) (p < 0.01). When a weaning technique was used, the weaning time was similar in both groups (3.5 +/- 3.9 days vs 3.6 +/- 2.2 days in the control group). Duration of MV was shorter in the protocol group (10.4 +/- 11.6 days) than in the control group (14.4 +/- 10.3 days) (p < 0.05). As a result, the ICU stay was reduced by using the weaning protocol (16.7 +/- 16.5 days vs 20.3 +/- 13.2 days in the control group, p < 0.05). We found no differences in reintubation rate (17 vs 14% in the control group) and need for tracheostomies (2 vs 8% in the control group). CONCLUSION: The implementation of a weaning protocol decreased the duration of MV and ICU stay by increasing the number of safe, direct extubations.

Effect of ranitidine on gastric intramucosal pH in critically ill patients.

OBJECTIVE: To determine whether ranitidine a) increases the values of gastric intramucosal pH (pHi) in critically ill patients, as determined by tonometry; b) reduces the variability of these measurements. DESIGN: Prospective, double blind, randomized, placebo-controlled study. SETTING: General Intensive Care Unit of a teaching hospital. PATIENTS: Twenty-five critically ill, mechanically ventilated patients requiring arterial catheter and nasogastric tube. INTERVENTIONS: Tonometer placement; blind, random administration of intravenous ranitidine (50 mg) or placebo. MEASUREMENTS AND MAIN RESULTS: Tonometer saline PCO2 (PCO2i), arterial blood gases, gastric juice pH and pHi were determined immediately before, and 2, 4, 6 and 8 h after, ranitidine (12 patients) or placebo (13 patients). Ranitidine significantly increased gastric juice pH, but did not affect PCO2i or pHi; pHi was 7.34 +/- 0.14 before ranitidine, and 7.30 +/- 0.12, 7.31 +/- 0.11, 7.31 +/- 0.14 and 7.31 +/- 0.12-2, 4, 6 and 8 h, respectively, after ranitidine administration (p = 0.55). Ranitidine did not modify the coefficients of variation of PCO2i or pHi, either. No significant changes in gastric juice pH, PCO2i or pHi were observed in the placebo group. CONCLUSIONS: In critically ill patients, ranitidine has no effect on pHi values, and does not increase the reproducibility of pHi measurements.

In vitro interferon gamma regulation of CCR-3 mRNA expression in peripheral blood leukocytes from atopic asthmatics.

Interferon gamma (IFN-gamma) exerts major pro-inflammatory, regulatory, and anti-inflammatory actions in immune defense responses. In asthma the infiltration of eosinophils, neutrophils, and lymphocytes is a critical event. Chemokines stimulate the migration of the susceptible subset of inflammatory cells. The chemokine receptors CCR-3 are mainly expressed in eosinophils, basophils, and Th2 cells. More recently it has been demonstrated that the IFN-gamma downregulates the expression of some chemokine receptors. IgE determinations were performed using an ELISA for total IgE Peripheral blood leukocytes from patients and controls were isolated by Ficoll-Hypaque gradient. The cells were incubated in the absence or presence of 500 IU/ml of recombinant human IFN-gamma for different times. After incubation the cells were washed and lyzed for reverse transcription-polymerase chain reaction (RT-PCR) analysis. RT-PCR was performed using a Perkin-Elmer kit. The amplified bands were run in 2% agarose gels and quantified. The basal levels of CCR-3 in asthmatic patients with IgE > 150 IU/ml tend to be higher than in controls. IFN-gamma down-regulates the expression of CCR-3 in peripheral blood leukocytes from asthmatics with IgE >150 IU/ml, when compared with the basal levels of expression. In conclusions, through the modification of the expression of CCR-3 in peripheral blood leukocytes from atopic asthmatics, IFN-gamma could exert a beneficial effect in patients with asthma, regulating the migration of some inflammatory cells involved in the pathogenesis of the disease.

[Selective pulmonary vasodilator effect of inhaled nitric oxide in a patient with pulmonary thromboembolism]. / Efecto vasodilatador pulmonar selectivo del óxido nítrico inhalado en un paciente con tromboembolismo pulmonar.

The increase in pulmonary vascular resistences in acute pulmonary thromboembolism (APT) is the consequence of anatomical obstruction and pulmonary artery constriction. The administration of inhaled nitric oxide (NO) may be therapeutically useful in acute pulmonary hypertension by APT given its limited vasodilator effect on pulmonary circulation. A patient with APT in whom this selective vasodilator effect was observed is presented. The authors suggest that the administration of inhaled NO may be a potentially beneficial coadjuvant therapy in acute pulmonary hypertension induced by APT.

Oral human recombinant epidermal growth factor in the treatment of patients with duodenal ulcer.

The epidermal growth factor has been shown to be mucoprotective and to accelerate healing of gastroduodenal ulcers in animals. A prospective, positively controlled clinical trial was conducted. Seventy five patients with duodenal ulcer were randomly distributed in three groups to receive oral human recombinant epidermal growth factor in 1% carboxymethyl cellulose at two different doses (450 mg or 600 mg/day), or cimetidine. Treatment was administered up to a maximum of 6 weeks. The most important assessment criteria was the proportion of patients healed after 2, 4 and 6 weeks of treatment determined by endoscopy. Treatment with both doses of epidermal growth factor showed a long-term healing effect in 76.5% at 6 weeks vs 92.5% with cimetidine (p = N.S.). The evolution of the clinical symptoms was similar in the three groups. Adverse reactions were not detected in any of the patients included in this study. To our knowledge, this is the first report on the oral use of epidermal growth factor in humans.

[Alpha interferon and Alzheimer's disease]. / Interferón alfa y enfermedad de Alzheimer.

INTRODUCTION: Alzheimer's disease (AD) is the commonest cause of dementia; its aetiology is unknown and there is non-specific treatment to detain the course of the disease. The interferons (IFN) are proteins which have antiviral, antiproliferative and immuno-modulating effects, and in the central nervous system these effects are mediated through the opiate receptors and the dopaminergic system. There is evidence that AD may be related to certain prion diseases and certain viruses, and that the IFN system has become deteriorated in this condition. OBJECTIVE: We present a review of patients with AD treated with alpha interferon. DEVELOPMENT: The first known case in the literature was that of a 69 year old man with definite AD (NINCDS-ADRDA) who was given alpha leucocytic IFN intrathecally and who initially was suspected of having Creutzfeldt-Jakob disease; after his treatment with IFN-alpha, his neurological signs were observed to have stabilized. Subsequently, the results of a controlled, randomized, clinical trial were analyzed for 16 patients with probable EA (NINCDS-ADRDA) treated with recombinant IFN-alpha 2b intramuscularly, in whom no changes in clinical and neurophysiological assessment were observed after a year of treatment. However, there was a significant improvement in one of the variables used to measure quality of life, together with a certain reduction in mortality in the patients treated with IFN-alpha. CONCLUSION: These results should be investigated in future studies in the light of current findings concerning the fact that, in the neurophysiological changes in AD, the pro-inflammatory cytokines, of which some of their numerous actions are blocked by IFN-alpha, may produce a deleterious effect on the course of AD.