Transgenic mice with chronically elevated luteinizing hormone are infertile due to anovulation, defects in uterine receptivity, and midgestation pregnancy failure.

Elevated levels of LH have been associated with infertility and miscarriage in women. Previously, we have reported generating a transgenic mouse model that hypersecretes LH. Female transgenics exhibit extensive pathology including enlarged, cystic, and hemorrhagic ovaries; elevated testosterone:estradiol ratios; and infertility primarily due to anovulation. Here we show that anovulation can be reversed in transgenics and that, despite development within a pathological ovary, oocytes from transgenics are remarkably healthy. Fertilized ova from transgenics are capable of normal development to term when transferred into nontransgenic pseudopregnant recipients. However, reciprocal transfers of nontransgenic embryos into transgenic recipients failed due to lack of uterine receptivity. In addition, while superovulated and mated transgenics appear to have normal early pregnancy, embryos are resorbed at midgestation due to maternal hormonal defects. Transgenic infertility can be rescued by ovariectomy with progesterone and estradiol replacement. These studies are particularly intriguing in light of data indicating an increased rate of miscarriage among women undergoing infertility treatments who are diagnosed with polycystic ovarian syndrome.

Expression of the AMP-activated protein kinase beta1 and beta2 subunits in skeletal muscle.

A heterotrimeric member of the AMP-activated protein kinase (AMPK) isoenzyme family was purified from rat skeletal muscle by immunoaffinity chromatography, consisting of an alpha2 catalytic and two non-catalytic subunits, beta2 and gamma1. The AMPK beta2 cDNA (271 amino acids (aa), molecular weight (MW)=30¿ omitted¿307, pI 6. 3) was cloned from skeletal muscle and found to share an overall identity of 70% with beta1 (270 aa, MW=30¿ omitted¿475, pI 6.0). In the liver AMPK beta1 subunit, Ser-182 is constitutively phosphorylated whereas in skeletal muscle beta2 isoform, we find that Ser-182 is only partially phosphorylated. In addition, the autophosphorylation sites Ser-24, Ser-25 found in the beta1 are replaced by Ala-Glu in the beta2 isoform. beta2 contains seven more Ser and one less Thr residues than beta1, raising the possibility of differential post-translational regulation. Immunoblot analysis further revealed that soleus muscle (slow twitch) contains exclusively beta1 associated with alpha2, whereas extensor digitorum longus muscle alpha2 (EDL, fast twitch) associates with beta2 as well as beta1. Sequence analysis revealed that glycogen synthase, a known AMPK substrate, co-immunoprecipitated with the AMPK alpha2beta2gamma1 complex.

Septic arthritis of the wrist.

Twenty-eight patients (two of them children) with septic arthritis of twenty-nine wrists were treated with early surgical drainage, parenteral antibiotics, and early motion after surgical decompression. The etiology was trauma in seventeen patients, and Staphylococcus aureus was the organism that was most commonly recovered on culture. In twenty-two patients (twenty-three wrists) who were followed for six months to nine years there were no recurrences. The results were evaluated in terms of range of motion, grip strength, and subjective complaints of discomfort and disability. Of the ten wrists with a good or excellent result, all had had the arthrotomy within ten hours after diagnosis, and of the thirteen with a fair or poor result, surgery had been delayed for sixteen hours or longer. The long-term results deteriorated in direct proportion to increasing time until treatment and the number of procedures performed.

Propeller injuries incurred in boating accidents.

Water skiing, boat racing, skin and scuba diving, as well as just pleasure cruising are increasing in popularity. As a result, the incidence of injuries secondary to motor propellers is becoming more frequent. In a 15-year period (1963 to 1978), the author has collected a total of 32 cases of propeller injuries. The some cases amputations were necessary and in other cases amputations occurred at the time of injury. Problems with bacterial flora (Pseudomonas sp.) occur in open sea water. Salt water enclosed near docks and fresh lake water may have many different organisms because of contamination with raw or treated sewage. Bacterial contamination was a problem in the majority of the cases. The initial handling of the wounds was important in the final outcome. Difficulties with prosthetic fitting and management have occurred. It is hoped that legislation requiring safety propellers and compulsory third-party presence in water ski boats will be forthcoming. A search of the orthopaedic literature both in English and foreign languages revealed sparse information referable to propeller injuries.

Women's perception of provider, social, and program support in an outpatient drug treatment program.

The purpose of this study was to explore perceptions of pregnant and parenting substance-abusing women in an outpatient drug treatment program regarding provider and social support. Also identified were aspects of the rehabilitation program perceived by the women as assisting them to maintain abstinence from substance use. Data were collected through a demographic questionnaire and a tool designed by the authors based on the Social Stress Model of Substance Abuse (Lindenberg et al., 1993) and the literature of social support. The majority of the women were satisfied with their social support from family and friends. Sixty-seven percent of the women felt the support received from medical providers were not adequate. Also, the majority of the women received no information on risks of drug use and pregnancy from their medical providers. The women felt the program helped maintain abstinence by providing education, coping mechanisms, resources, 12-step programs, and spiritual guidance.

Bilateral buccal flaps with double opposing Z-plasty for wider palatal clefts.

Described is a technique that has evolved from the challenges of closure of larger cleft palate defects and that we are now using in preference over other techniques to repair a wide variety of clefts. Soft-palate closure and muscular sling reconstruction are accomplished using a modified Furlow technique. An associated cleft of the hard palate and the gaps produced by posterior displacement of the reconstructed soft palate are closed by adding tissue, buccal flaps, rather than by closure under tension or leaving residual raw surfaces. Palate lengthening is achieved both by the Z-plasty effect and by the interposition of buccal flaps between the hard and soft palate. Seventy-six palates have been repaired using this procedure. There were three postoperative fistulas.

Dupuytren's contractures in a black patient.

We report a case of bilateral Dupuytren's contracture occurring in a black patient, apparently the sixth reported occurrence.

A model for the cleft lip nasal deformity.

The underlying pathology of the cleft lip nasal deformity has yet to be fully realized, and cleft lip rhinoplasty continues to challenge the reconstructive surgeon. A new model is proposed, which is composed of elements that represent known anatomical structures of the nose. These structures are considered elemental to the mechanism of the primary cleft lip nasal deformity. The lobule is reduced to four arches. Five points on the skull provide foundations for these arches, which react interdependently to extrinsic forces and positional change. When certain changes are imposed on the model, predictable alterations in the configuration of the model imitate the observed deformities in the spectrum of the cleft lip nasal deformity, unilateral and bilateral, mild through severe. The model is described with illustrations, anatomic dissection, physical models, and selected clinical cases. A better understanding of the mechanisms of the cleft nasal deformities can be obtained through analysis of the model.

Controlled tissue expansion of a groin flap for upper extremity reconstruction.

A large upper extremity defect in an 8-year-old girl was resurfaced with an expanded groin flap. Tissue expansion allowed complete coverage of the defect while minimizing the donor deformity. Pretransfer expansion of pedicled flaps offers an alternative to free-flap reconstruction of complex upper extremity defects. This is especially valuable in the pediatric patient, in whom donor-site morbidity can be significant.

The dorsal skin-flap model in the rat: factors influencing survival.

Several authors have postulated that the standard McFarlane-type dorsal rat flap model can survive as a graft. Therefore, in an effort to better understand the metabolic support governing the survival of this flap, five flap designs on the dorsal surface of the rat were studied. Each was manipulated to control progressively for the metabolic support to the flap by means of skin-graft and/or skin-flap physiology. The flap designs included (1) a standard McFarlane flap (n = 10), (2) a full-thickness "flap" graft (n = 10), (3) a McFarlane flap separated from the bed with plastic sheeting (n = 9), (4) a McFarlane flap separated from the bed by closing the wound beneath the flap (n = 29), and (5) flaps raised as in group 4 after a 2-week delay procedure (n = 9). Based on direct comparisons of both the pattern of necrosis and the surviving surface area in each group, we conclude that (1) the distal aspect of the dorsal rat flap can survive as a graft when in contact with the underlying bed, (2) the "take" of the flap as a graft is variable, and (3) to serve as a reasonable indicator of human flap behavior, the skin-graft effect must be controlled for by separating the flap from the underlying bed.

The personal experience of pregnancy for African-American women.

This study describes the personal experiences of pregnancy for African-American women. Data were obtained from two group interviews with four African-American nurse-midwives who had experienced pregnancy and had extensive professional experience in the provision of health care services to pregnant African Americans. Three major themes were constructed from the interview narratives. The first concerned the experience of pregnancy as a transition experience from childhood to adulthood and from womanhood to motherhood, involving heightened senses of maturity, self-esteem, and intimacy. The second identified stresses experienced by African-American women, including the lack of material resources and emotional support. The last theme concerned the provision of effective support in pregnancy. The significance of interpersonal relationships with the pregnant women's mothers, other significant women, and their partners was described. Implications for practice included suggestions for the provision of effective emotional support from health care professionals such as attentive listening and the elimination of environmental factors that communicate lowered personal value.

Clinical practice guidelines: implications for use.

The differences between standards and clinical practice guidelines are discussed. Implications for using guidelines in nursing practice in defining scope of practice, evaluating careless or negligent practice, practicing outside of clinical guidelines, and using clinical guidelines for cost containment are presented.

The major determinant of exendin-4/glucagon-like peptide 1 differential affinity at the rat glucagon-like peptide 1 receptor N-terminal domain is a hydrogen bond from SER-32 of exendin-4.

BACKGROUND AND PURPOSE: Exendin-4 (exenatide, Ex4) is a high-affinity peptide agonist at the glucagon-like peptide-1 receptor (GLP-1R), which has been approved as a treatment for type 2 diabetes. Part of the drug/hormone binding site was described in the crystal structures of both GLP-1 and Ex4 bound to the isolated N-terminal domain (NTD) of GLP-1R. However, these structures do not account for the large difference in affinity between GLP-1 and Ex4 at this isolated domain, or for the published role of the C-terminal extension of Ex4. Our aim was to clarify the pharmacology of GLP-1R in the context of these new structural data. EXPERIMENTAL APPROACH: The affinities of GLP-1, Ex4 and various analogues were measured at human and rat GLP-1R (hGLP-1R and rGLP-1R, respectively) and various receptor variants. Molecular dynamics coupled with in silico mutagenesis were used to model and interpret the data. KEY RESULTS: The membrane-tethered NTD of hGLP-1R displayed similar affinity for GLP-1 and Ex4 in sharp contrast to previous studies using the soluble isolated domain. The selectivity at rGLP-1R for Ex4(9-39) over Ex4(9-30) was due to Ser-32 in the ligand. While this selectivity was not observed at hGLP-1R, it was regained when Glu-68 of hGLP-1R was mutated to Asp. CONCLUSIONS AND IMPLICATIONS: GLP-1 and Ex4 bind to the NTD of hGLP-1R with similar affinity. A hydrogen bond between Ser32 of Ex4 and Asp-68 of rGLP-1R, which is not formed with Glu-68 of hGLP-1R, is responsible for the improved affinity of Ex4 at the rat receptor.