Family medicine month in a university-based program: establishing a family medicine identity

"Family Medicine Month," a rotation forfirst-year residents, was developed to clarifyfirst-year residents'new roles as family physicians. The rotation explored the meaning and history of the specialty, as well as teaching core family medicine clinical and behavioral skills. Twenty residents who participated in the rotation in 1999 and 2000 indicated satisfaction with the rotation and endorsed its usefulness. They also reported greater self efficacy in performing family practice skills after the rotation, compared with before the rotation. Results suggest that a curriculum based on the context of family medicine as a specialty enhances resident satisfaction and self efficacy.     

Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 16: bone graft extenders and substitutes

Despite the large volume of animal data regarding the use of synthetic bone graft substitutes or extenders, there are very few data regarding the use of these substances for fusion in lumbar degenerative disease. The best available data indicate that rhBMP-2 is a viable alternative to autograft bone for interbody fusion procedures. This same substance may also be a viable alternative to autograft for PLF; however, definitive medical evidence is not yet available. There is little, if any, medical evidence to support the use of other biological agents at the present time. As promising new compounds are brought to market, well-designed cohort studies and randomized trials will be required to determine the actual usefulness of these compounds in clinical practice. It is important not to generalize the results obtained with one preparation or application to different preparations or applications. The use of synthetic calcium phosphate ceramics as graft extenders appears to be reasonable in certain situations. The medical evidence available regarding their use is limited and of poor quality. Further study will be required to establish their utility for use in spinal fusion.     

Hydroxyurea exerts a cytostatic but not immunosuppressive effect on T lymphocytes

OBJECTIVE: To demonstrate that, despite a dose-dependent cytostatic effect, hydroxyurea (HU) does not have immunosuppressive effects. METHODS: The effects of HU on T lymphocyte proliferation parameters, activation phenotype and cytokine production were examined in vitro after exposure to clinically relevant concentrations of HU (10, 50, and 100 micromol/l). The effects of HU in vivo on CD4 T cell counts, viral load, activation phenotype and virus-specific response were examined in 17 Rhesus macaques infected with SIV(mac251) and randomized into three groups: untreated controls; treated with (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) and didanosine (ddI) only; and treated with PMPA, didanosine, and HU. RESULTS: The in vitro inhibition of T lymphocyte proliferation confirmed the cytostatic effect of HU, with a linear dose-dependent effect; however, no relevant differences were found in the expression of activation markers between treated and untreated controls. Both T helper type 1 and type 2 cytokine production were enhanced by HU. Consistent with the in vitro results, a blunted increase of peripheral CD4 T cells was observed in vivo in the HU group, without relevant effects on the expression of activation markers, and SIV-specific T cell responses were not affected by HU. CONCLUSIONS: Hyper-proliferation of T-lymphocytes is a major factor contributing to HIV pathogenesis. HU exerts a cytostatic effect on T lymphocytes, without altering their activation and apparently without having an immunosuppressive effect. The increase in cytokine production at the single cell level might compensate for the decrease in the percentage of activated CD4 T lymphocytes, without overall impairment of HIV-specific immune responses.     

The evolution of senescence in natural populations of guppies (Poecilia reticulata): a comparative approach

Model organisms like Drosophila melanogaster or Caenorhabditis elegans have revealed genes that influence senescence and the evolvability of senescence. We are interested instead in evaluating why and how senescence evolves in natural populations. To do so, we are taking the ecological geneticist's perspective of comparing natural populations that differ in factors that are predicted to influence the evolution of senescence and are evaluating whether senescence has evolved in the predicted fashion. We are also manipulating the environment to evaluate more directly the evolution of senescence. Guppies (Poecilia reticulata) are found in streams throughout the Northern Range mountains of Trinidad. Natural populations experience large differences in mortality rate as a consequence of the predators with which they co-occur. We have already shown, both with comparative studies and manipulations of the distribution of guppies and their predators, that the early life history evolves very rapidly in response to these differences in mortality. For example, high adult mortality rates select for individuals that develop more rapidly, produce their first litter of young at an earlier age, and devote more of their available resources to reproduction for the remainder of their lives. These changes were predicted by independently derived theory. Aspects of this same theory also predict how the late life history and senescence should evolve. Specifically, theory predicts that the populations that experience low mortality rates should also experience delayed senescence and longer life spans relative to those that experience high mortality rates. We are currently evaluating these predictions with representatives from two high-predation and two low-predation environments. Our presentation will focus on our pilot study, which evaluated life span, lifetime reproduction, and the patterns of aging in our laboratory populations. We will also report on the progress in our ongoing comparative studies of senescence in natural populations.     

Pelvic neoplasms in children

The pelvis of the infant and child has different anatomic relationships than the adolescent or adult pelvis, and the knowledge of congenital anomalies of the rectum and bladder can assist in treating the primary neoplasms of the pelvis. The most common neoplasms are rhabdomyosarcomas of the bladder, prostate, and vagina; sacrococcygeal teratoma; and the germ cell tumors, including teratomas, endodermal sinus tumors, and the choriocarcinomas. Rapidly improving chemotherapy for all of these lesions has resulted in a changed role for the surgeon. Less radical resection of these tumors is being performed whereas it is necessary to have more precise histologic and genetic identification of the tumor and the specific anatomic location and extent of the tumor in the pelvis. Survival for all types of childhood pelvic neoplasms has improved dramatically under the influence of the combined children's cancer study groups, which have been functioning for the last 20 years. Because of the complexities of diagnosis and treatment of these pelvic neoplasms in childhood and because the survival rates have dramatically improved with the most current therapy, these children should be cared for in a children's center that is part of the major children's cancer study groups.     

Isolatin and characterization of a viable deletion mutant of adenovirus type 3

The effects of amber mutations in the 25 known genes of phage T1 on phage DNA replication were examined by sedimentation analysis of pulse-labelled DNA extracted from infected nonpermissive cells. Five groups of mutants were identified according to their DNA phenotype. Group I comprises am20 (gene 1) and am5 (gene 2) which are totally defective in DNA synthesis as previously shown by D. Figurski and J. R. Christensen (1974, Virology59, 397–407). Group IIA also consists of two mutants, am201 (gene 3.5) and am23 (gene 4), both of which fail to make concatemeric DNA. Group II includes am41(gene 3), am15 (gene 5), am18 (gene 6), am35 (gene 7), am32 (gene 8), am13 (gene 9), am19 (gene 10), am29 (gene 11), am304 (gene 11.5), and am37 (gene 12). This group, represented predominantly by genes controlling tail formation, exhibits a wild-type pattern in which concatemerie DNA is synthesized and then processed to unit-length molecules. Group III mutants are all defective in head formation and accumulate concatemeric DNA molecules. This group contains am10 (gene 13), am216 (gene 13.7), am45 (gene 14), am246 (gene 14.5), am11 (gene 15), am4 (gene 16), am7 (gene 17), and am30 (gene 18). Group IV is represented by a single mutant, am283 (gene 13.3), with a sedimentation pattern intermediate between that of Group II and Group III mutants. It is not known if am283 is defective in concatemer formation or concatemer processing.     

Short insertion in a hemoglobin chain: Hb Esch,an unstable alpha1 variant with duplication of the sequence Ala65-Leu-Thr-Asn68

Hemoglobin (Hb) Esch, is an alpha1 variant, expressed at less than 5%, resulting from the duplication of the 12 nucleotides corresponding to CD65 through 68. The effect of this insertion is the repetition of the sequence Ala-Leu-Thr-Asn, which corresponds to the last turn of helix E. In this variant the presence of a one-turn elongated helix E causes instability and increased ligand affinity. Hb Esch was characterized by DNA sequencing and confirmed by electrospray mass spectrometry. Functional studies were performed by flash photolysis measurements on a fraction isolated by flatbed isoelectric focusing, which was enriched in the abnormal hemoglobin. Similar to other alpha chain variants due to short insertion (or deletion), Hb Esch probably results from a slipped mispairing mechanism. The stability of such modified proteins depends upon the region which is added or deleted and usually is more stable when involving a flexible loop or complete helix turn(s) near by.     

Hysterosalpingography in the preoperative evaluation of tubal anastomosis candidates

The value of the hysterosalpingogram (HSG) in the investigation of women requesting reversal of tubal sterilization has never been established. Accordingly, we reviewed the preoperative HSGs performed on 54 women and the surgical findings of these and 27 additional patients who underwent laparoscopy and/or laparotomy for tubal anastomosis. The observation of interstitial, isthmic, and ampullary obstruction by HSG correctly correlated with surgical findings in 12%, 94%, and 69% of cases, respectively. The decision to perform an anastomosis was made in 14 of 17 (82.4%) tubes with interstitial obstruction, 45 of 51 (88.2%) tubes with isthmic occlusion, and 26 of 36 (72.2%) tubes with ampullary occlusion. When distal tubal occlusion was demonstrated by HSG (36/104 tubes, 34.6%), 10 had no repairable ampullary segments. The site of tubal occlusion on HSG was not predictive of a repairable tube. We conclude that the routine HSG is not warranted in the preoperative evaluation of candidates for tubal anastomosis.