Anabolic Androgenic Steroids in the Treatment of Acquired Aplastic Anemia

The results of the oral administration of high doses of anabolic hormones(oxymetholone, metholone or dromostanolone and methenolone) in the treatment of 69 patients (14 children and 55 adults) with aplastic anemia arepresented. Remission rates were 48 per cent for the whole group and 70 percent for those treated for more than two months. Twenty-two cases havebeen in remission for 1 to 5 years without maintenance therapy. Eight othersrelapsed 2 to 4 months after stopping therapy, but responded to the reinstitutionof medication. However, four of them have had several relapses and appearto require permanent therapy. In the other four, the second remission hascontinued for 6 to 40 months. Clinical response was first noted after 0.6 to 6months of therapy and was characterized by a rise of hemoglobin to normallevels with a variable degree of improvement in the leukopenia and thrombocytopenia. The number of neutrophils and platelets rose to normal levelsin over a third of the cases which responded. Response to therapy was not relatedto age, sex, etiology, degree of pancytopenia or bone marrow cellularity. Thethree anabolic hormones seemed equally effective.

Nine patients became clinically jaundiced during therapy; four recoveredand five died. Abnormalities in liver function existed before treatment in threeof those who died. In four of these five cases, the liver lesion was due to anindependent cause: viral hepatitis in one, gram negative septicemia andnecrotic colitis in two and thiazide toxicity in the fourth. No autopsy was performed in the other case and the etiology of his liver damage could not bedetermined. Three of the fatal cases were taking a non-17-alkylated steroid.Other patients presented mild, subclinical and nonprogressive rises in serumdirect bilirubin and in BSP retention. The frequency of liver function changeswas greater (80 per cent) with oxymetholone than with the other twonon-17-alkylated steroids (26 per cent). The changes induced with the formerdrug regressed completely when metholone or methenolone was substituted.Other side effects were amenorrhea and mild virilization; no growth retardation or changes in bone maturation were observed.

Our results suggest that some anabolic adrogenic steroids may be moreuseful than testosterone in the treatment of aplastic anemia.

Submitted on October 2, 1968 Accepted on February 24, 1969     

Tetralogy of Fallot Repair with Minimal or No Ventriculotomy

Twenty-four consecutive patients with the tetralogy of Fallot underwent repair from March 25, 1985 to March 24, 1986. Correction was achieved without a ventriculotomy in 8 patients, necessitated a minimal ventriculotomy in 8, and a formal right ventriculotomy incision was required in the other 8. There were no early or late phase deaths-0% (70% C.L. 0%-7%). Post repair right ventricular to left ventricular pressure ratios were not significantly different between the three groups (p = 0.85). The 16 patients (66%) who underwent repair without a formal ventriculotomy were found to have severe hypertrophy of the infundibular septum as the primary etiology for right ventricular outflow tract obstruction. The other 8 patients (34%), who required a transventricular approach to the repair, were all found to have predominantly hypoplasia of the outflow tract and not hypertrophy. We conclude that repair of the tetralogy of Fallot can frequently be accomplished with no or a minimal ventriculotomy, and the results are satisfactory. Herein is described the operative approach to this procedure.     

Maxillary dental anomalies in children with cleft lip and palate: a controlled study

International Journal of Paediatric Dentistry 2010; 20: 442–450 Objective. To evaluate the prevalence of dental abnormalities of the primary and permanent maxillary dentitions in children affected by unilateral (UCLP) and bilateral (BCLP) cleft of the lip and palate. Methods. One hundred and fifty‐six Caucasian patients (64 females and 92 males) affected by non‐syndromic UCLP or BLCP were selected. A control sample of 1000 subjects (482 males and 518 females) without CLP was selected. All comparisons were carried out by means of z‐tests on proportions. Results. The prevalence rate for missing primary lateral incisors in UCLP subjects was 8.1% and it was 27.9% for the permanent lateral incisors. In BLCP subjects, the prevalence rates were 17% for the primary lateral incisors and 60% for the permanent lateral incisors. The second premolar was absent in 5.4% of UCLP subjects and in 8.8% in the BCLP sample. The statistical analysis revealed significant differences for the prevalence rates of all dental anomalies compared with the control group except for second premolar agenesis. Conclusions. In both UCLP and BCLP subjects the most prevalent missing teeth were the lateral incisors. The dental anomalies occurred predominantly in the cleft area, thus suggesting that the effect of the cleft disturbance is more local than general on the dentition.     

Multiple Shocks Affect Thoracic Electrical Impedance During External Cardioversion of Atrial Fibrillation

Background: Thoracic impedance (TI) influences the success of external cardioversion (ECV) or defibrillation because current intensity traversing the heart is inversely related to TI. Experimental data suggest that TI decreases after multiple shocks. We undertook a clinical study to determine changes of TI values in patients with atrial fibrillation or flutter requiring ECV. Methods: We enrolled 222 consecutive patients (age 73 ± 11 years; males 67%; body weight 75 ± 13 kg) who underwent ECV between January 2004 and February 2007. Biphasic shocks were delivered through adhesive pads placed in the anteroposterior position. The initial energy was set at 1 J/kg, with progressive increases up to a maximum of 180 J in case of failure. In the last 39 elective patients, plasma concentration of interleukin‐6 (IL‐6) and tumor necrosis factor (TNF)‐α were determined before and 6 hours after ECV. Results: Sinus rhythm was restored in 202 patients (91.0%). Of these, 155 (69.8%) required more than one shock (on average, 2.5 ± 1.5 shocks/patient). Final values of energy and peak current intensity were 136 ± 47 J and 50 ± 14 A, respectively. TI decreased significantly by 6.2% from baseline after ≥2 shocks (P < 0.001). The absolute reduction was correlated with baseline TI, number of delivered shocks, and hemoglobin oxygen saturation. IL‐6 and TNF‐α increased with ECV (P < 0.001 and P = 0.014, respectively). Conclusions: TI decreases significantly after multiple shocks, possibly by activation of acute inflammation.     

SYNTHETIC ENKEPHALINS Addicting Properties and Conformational Studies in Solution

The addicting properties of [Leu⁵]-enkephalin in mice are conserved in the l -Ser³ analogue and lost both in the l -Ser² analogue and in all the l -Cha⁴ derivatives of the above peptides. Fluorescence measurements in water show the presence of hydrogen-bonded tyrosyl OH groups in [Leu⁵] -enkephalin and in its l -Ser² analogue. The Phe⁴/Cha replacements do not influence these equilibria, but they affect the near u.v. dichroism of the hydrogen bonded tyrosyl residues. In the peptide absorption region in water solution, only [Leu⁵]-enkephalin and its cyclohexylalanyl derivative show a positive dichroism towards high frequencies, which is maintained in 8 M urea. No clear relation is found between conformations) in solution and biological activity. A II' β-turn, with residues in positions 2 and 3 at the corners, is suggested for the conformation of enkephalin bound to the receptors involved in the bioassay here used.