Localization of IGF-I and IGF-I Receptor mRNA inSparus aurataLarvae

Studies of the ontogeny of IGF-I mRNA during embryonic and larval development of the gilthead sea breamSparus auratashowed its expression during these early developmental stages. The present study appliesin situhybridization to localize IGF-I and IGF receptor mRNAs in 16-day larvae ofS. aurata.Paraffin sections were hybridized with homologous RNA probes labeled by [³⁵S]UTP. IGF-I mRNA expression was found mainly in chondrocytes, in both the gill arches and cranial cartilage, in skeletal muscle, in the brain, in the pancreas, in the retina, and in the epithelial cells surrounding the lens. A strong positive reaction for IGF receptor mRNA was found in skeletal muscle, in the pancreas, and in the lymphoid tissue found in the intertubular tissue of the kidney. Signals were less intense in brain and chondrocytes. It is suggested that in teleosts, as in higher vertebrates, IGF-I may be involved in the regulation of tissue growth and differentiation in an autocrine/paracrine manner.     

Sarcoidosis presenting with prolonged fever in a patient with sickle cell anemia.

Although the leading causes of fever and pulmonary infiltrates in sickle cell patients are acute bacterial pneumonia and the acute chest syndrome, the former is usually responsive to antibiotics and not protracted, and the clinical course of the latter is short and self-limited. A patient with sickle cell anemia presented with fever and pulmonary infiltrates of several weeks duration that were unresponsive to antibiotics. Gross endobronchial abnormalities were noted on bronchoscopy, and the biopsies were consistent with sarcoidosis. The diagnosis of sarcoidosis can be difficult to establish in a patient with sickle cell anemia and protracted fever since both disorders are associated with chronic interstitial changes on the chest radiograph as well as restrictive physiology.     

Heat probe thermocoagulation as a substitute for surgical intervention to arrest massive peptic ulcer hemorrhage: an experience in 153 cases

In a period of 2 years 7 months, we performed heat probe (HP) thermocoagulation in 153 cases of massive peptic ulcer hemorrhage. The male/female sex ratio was 125/28. The average age was 57.6 +/- 1.3 years (mean +/- SEM; range, 17 to 88). There were 69 cases (45.1%) of spurting hemorrhage, 50 cases (32.7%) of oozing hemorrhage, and 34 cases (22.2%) of nonbleeding visible vessels. Seventy-seven patients (50.3%) were in shock before therapy. After therapy we obtained initial success in 147 cases (96.1%). Rebleeding episodes occurred in 23 patients (15.6%) within 1 month after therapy. Nineteen patients received a second therapy, and treatment in 15 of these cases (78.9%) was ultimately successful. Finally, treatment in 142 cases (92.8%) was ultimately successful. The duration of hospitalization was 6.3 +/- 0.4 days (mean +/- SEM). After discharge all patients were followed at the outpatient department for at least 1 month. Sixty-seven patients were followed endoscopically for at least 2 to 3 months after therapy. Fifty-six patients (83.6%) had a healed scar at the previous bleeding site 2 months after therapy, and 62 patients (92.5%) had a healed scar 3 months after therapy. We conclude that HP thermocoagulation is an ideal and reliable modality of therapeutic endoscopy in arrest of massive peptic ulcer hemorrhage. HP thermocoagulation may become the first choice of therapy for massive peptic ulcer bleeding in the near future.     

Laparoscopic appendicectomy — A successful operation in adults and children

Laparoscopic appendicectomy has been the subject of several encouraging reports, but has not as yet gained widespread acceptance. We present a series of 159 consecutive laparoscopic appendicectomies performed, over a 4 yr period, in both adults and children. We find the procedure as safe as its open counterpart, with patients fit to leave hospital within the same time period. Perforated appendices were amenable to this procedure, and the location of the appendix did not alter the outcome. Children responded as well as adults post-operatively. Obesity may be an indication for this form of treatment. Removal of displaced faecoliths associated with perforated appendicitis is a difficult technical problem in less than 5 per cent of patients.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Stimulation of protein phosphatase activity by insulin and growth factors in 3T3 cells.

Incubation of Swiss mouse 3T3-D1 cells with physiological concentrations of insulin resulted in a rapid and transient activation of protein phosphatase activity as measured by using [32P]phosphorylase a as substrate. Activation reached a maximum level (140% of control value) within 5 min of addition and returned to control levels within 20 min. The effect of insulin was dose-dependent with half-maximal activation occurring at approximately 5 nM insulin. This activity could be completely inhibited by addition of the heat-stable protein inhibitor 2, which suggests the presence of an activated type-1 phosphatase. Similar effects on phosphatase activity were seen when epidermal growth factor and platelet-derived growth factor were tested. These results suggest that some of the intracellular effects caused by insulin and growth factors are mediated through the activation of a protein phosphatase.     

Phase I and pharmacologie study of liposomal daunorubicin (DaunoXome)

Summary We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial doseescalation steps from 10 to 60 mg/m². At 80 mg/m², two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m². Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m² in previously treated and 120 mg/m² of DaunoXome in previously untreated patients with solid tumors.EDW is supported in part by ACS award 92-14-1     

Inhibition of bronchoconstriction by pituitary adenylate cyclase activating polypeptide (PACAP 1-27) in guinea-pigs in vivo.

1. We studied the inhibitory effect of pituitary adenylate cyclase activating polypeptide (PACAP 1-27) on the increase in total pulmonary resistance (RL) caused either by allergen or histamine in anaesthetized, ventilated guinea-pigs. 2. PACAP 1-27 given via i.v. infusion (0.045-4.5 nmol kg-1 min-1) dose-dependently reduced the increase in RL caused by inhaled ovalbumin and histamine. At the highest dose, PACAP 1-27 prevented the increase in RL caused by ovalbumin and histamine completely. Infusion of PACAP 1-27 and the beta 2-adrenoceptor agonist, salbutamol (0.045-4.5 nmol kg-1 min-1) inhibited the increase in RL similarly, but salbutamol increased the heart rate more than PACAP 1-27. 3. PACAP 1-27 and salbutamol given via inhaled aerosol (0.1 mM, 20 breaths) significantly reduced the increase in RL caused by histamine infused i.v., whereas aerosolised sterile saline did not. Both PACAP 1-27 and salbutamol caused bronchodilator effects within 1 min of drug inhalation and these effects remained throughout the 20 min of study. 4. Because PACAP 1-27 produced significant bronchodilatation and rapid onset of sustained action in vivo and without pronounced cardiovascular side effects, we conclude that this peptide may have therapeutic potential as a bronchodilator.