Hormonal therapy of cryptorchidism. A randomized, double-blind study comparing human chorionic gonadotropin and gonadotropin-releasing hormone

We conducted a randomized, double-blind study comparing intranasal gonadotropin-releasing hormone (1.2 mg per day for 28 days) with parenteral human chorionic gonadotropin (3300 IU per week for four weeks) in the treatment of cryptorchidism in 33 boys one to five years old (29 with unilateral and 4 with bilateral cryptorchidism). Testicular descent into the scrotum occurred in 3 of the 16 patients (19 percent) treated with gonadotropin-releasing hormone and in 1 of the 17 (6 percent) treated with human chorionic gonadotropin (P = 0.23). The mean luteinizing hormone and testosterone levels were similar in both groups before treatment. During treatment, the testosterone levels were significantly increased in both groups, but higher levels occurred in the group treated with human chorionic gonadotropin (P less than 0.05). In a parallel (but uncontrolled) study of five boys with retractile testes (defined as a nonscrotal testis that could be manipulated into the bottom of the scrotum) who were originally excluded from the main protocol but were treated with the same regimen of human chorionic gonadotropin, descent into the scrotum occurred in all patients. We conclude that hormonal therapy with either gonadotropin-releasing hormone or human chorionic gonadotropin is, in most cases, ineffective in promoting testicular descent of true cryptorchid testes. However, short-term treatment with human chorionic gonadotropin is very effective in producing descent of retractile testes. These results suggest that the wide discrepancies in apparent efficacy in previous trials of hormonal therapy of cryptorchidism may have been due to inclusion in those studies of various proportions of patients with retractile testes.     

Nodular mixed lymphoma: results of a randomized trial failing to confirm prolonged disease-free survival with COPP chemotherapy

Fifty-two patients with stage III or IV nodular mixed lymphocytic- histiocytic lymphoma (NM) were entered on a prospective randomized trial comparing cyclophosphamide-prednisone (CP) to either COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or BCVP (BCNU, cyclophosphamide, vincristine, prednisone). The COPP regimen utilized in this Eastern Cooperative Oncology Group (ECOG) trial was similar to the four-drug regimen C-MOPP reported by the National Cancer Institute to achieve prolonged relapse-free survival in this histology. No significant differences in complete response rates, response duration, or overall survival were noted among the three regimens. A pattern of continuous late relapse was observed for all three chemotherapy programs. Although 11 of the 18 (61%) COPP patients achieved a complete response, only 3/11 (27%) remain disease-free with a median follow-up of over 3 yr. However, two of these three long-term complete responders have died with no clinical evidence of recurrent disease. The COPP patients received 84% of the calculated ideal doses of cyclophosphamide and 78% of the ideal dosage of procarbazine. Grade 3-4 hematologic toxicity was noted in 22% of the COPP group, 36% with BCVP, and 0% for the CP patients. We were unable to confirm the ability of COPP to achieve durable complete remissions in NM lymphoma. The cyclophosphamide-prednisone combination was equally effective when compared with COPP and BCVP, but produced minimal toxicity.     

Surface antigens on malignant Sezary and T-CLL cells correspond to those of mature T cells

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T- cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sezary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T- chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.     

Studies on In Vitro DNA Synthesis Purification of dna C Gene Product Containing dna D Activity from Escherichia coli

The conversion of varphiX174 single-stranded DNA to duplex DNA by extracts of E. coli requires products of the E. coli DNA replication genes. By use of this complementation system, the dna C gene product has been purified from wild-type E. coli as well as from a dna C temperature-sensitive mutant. The latter preparations are temperature sensitive when compared to the wild-type gene product. The dna C and dna D gene products copurify, have similar characteristics, are both temperature sensitive in preparations from dna C temperature-sensitive cells, and are both undetectable in preparations from dna D temperature-sensitive cells.     

Mechanism of elongation of primed DNA by DNA polymerase delta, proliferating cell nuclear antigen, and activator 1.

In the presence of a single-stranded-DNA-binding protein (SSB), the elongation of primed DNA templates by DNA polymerase delta (pol delta) is dependent on ATP and two protein factors, activator 1 (A1) and proliferating cell nuclear antigen (PCNA). We have examined the interaction of these proteins with (dA)4500.(dT)12-18 by measuring their ability to form stable complexes with this DNA. In the presence of ATP, A1, PCNA, and pol delta formed a stable complex with DNA that could be isolated by gel filtration. Incubation of the isolated complex with dTTP resulted in the synthesis of poly(dT). While ATP was required for the formation of this complex, it was not required for the subsequent elongation of DNA. The temporal requirements for complex formation were determined. A1 was found to bind first, followed by the ATP-dependent addition of PCNA to the A1.DNA complex, while pol delta was added last. Each of these complexes could be isolated by gel filtration, indicating that they possessed a high degree of stability. The binding of PCNA to the A1-SSB-coated primed DNA occurred with adenosine 5'-[gamma-thio]triphosphate as well as ATP. However, the binding of pol delta to the PCNA.A1-DNA complex was observed only when the latter complex was formed in the presence of ATP. The complete complex was formed after incubation at 37 degrees C for 2 min, whereas no complex was detected after incubation at 0 degree C. These results indicate that these proteins act in a manner analogous to the accessory proteins that play critical roles in the elongation reaction catalyzed by T4 phage DNA polymerase and Escherichia coli DNA polymerase III.     

Concomitant T-cell receptor alpha and delta gene rearrangements in individual T-cell precursors.

A debate has recently surfaced concerning the degree of precommitment attained by alpha beta and gamma delta T-cell precursors prior to T-cell receptor (TCR) gene rearrangement. It has been suggested that precursors may be precommitted to rearrange either alpha or delta genes, but not both, thus giving rise to alpha beta- and gamma delta-producing T cells, respectively. Alternatively, the precursors may be flexible with regard to potential TCR gene rearrangements. To address this controversy, the gene rearrangements among a group of T-cell hybridomas from fetal, newborn, and early postnatal mouse thymi were examined. Six probes spanning the delta and alpha loci were used in Southern blot analyses to characterize the rearrangements which occurred on homologous chromosomes in each cell. Although homologous chromosomes often rearranged in synchrony within the alpha locus, a number of hybridomas were found which had retained a delta rearrangement on one chromosome and an alpha rearrangement on the second. Results show that a precommitment by T cells to rearrange delta or alpha genes in a mutually exclusive manner is not an absolute feature of mouse thymocyte development.     

Postbariatric surgery breast reshaping: the spiral flap

INTRODUCTION: After massive weight loss, the breasts have poor shape, projection, and skin elasticity. Breast reshaping is recognized as difficult and may require excess nearby tissues. As the senior author's approach evolved over the past 4 years, breast reshaping with the spiral flap became integral to an upper body lift. MATERIALS AND METHODS: After the weight loss has stabilized, body contouring surgery has been performed on 53 patients over a 3-year period. Six patients had mastopexy and/or augmentation only. Eighteen patients had spiral flap breast reshaping as part of an upper body lift. This lift is a reverse abdominoplasty that ends along the inframammary fold incision of the Wise pattern mastopexy and continues laterally to along the back roll. Excess tissue from the epigastrium and lateral back roll is deepithelialized and used for augmentation. These flap extensions of the central breast pedicle are spiraled around the breast for augmentation, shaping, and suspension. When more tissue is needed, saline-filled silicone implants have been used, preferably during a second stage. RESULTS: Follow up of this initial group ranged from 4 to 28 months with a mean of 11 months. In this initial effort, 14 of the 18 were pleased. In 3 patients, subsequent bilateral saline implants further augmented the breasts. Tip fat necrosis was evident by firmness of the tissues in 3 patients and resolved in all but 1. That 1 patient had operative debridement of the distal 50% of the flaps followed by saline-filled silicone implants. One patient was disappointed with the back scar. Two patients dislike the shape and fill of their breast and have not returned for revision. CONCLUSION: During 3 years of focused clinical activity, we have evolved the spiral flap reshaping with upper body lift into a comprehensive, effective, satisfying, and safe esthetic contouring of the breast and upper torso after massive weight loss performed with an upper body lift.     

Evaluating the influence of prostate-specific antigen kinetics on metastasis in men with PSA recurrence after partial gland therapy

Purpose

Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir + 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy.