Risk factors for above-knee amputations in diabetes mellitus

BACKGROUND: Above-knee amputation (AKA) is a common complication in diabetics, mostly after one or more lower level amputations (LEAs) have been done. The aim of this study was to identify risk factors for AKAs among diabetics. METHODS: We abstracted 1,800 medical records of hospitalizations for LEA. Kaplan's comorbidity classification was used to rank disease severity. We used both univariate and multivariate models to identify risk factors for AKA. RESULTS: Of the 1,043 diabetic amputees in this study, 22% had AKA. Variables associated with AKA were locomotor impairment, severe anemia, history of lower extremity bypass surgery, body mass index (BMI) < 20 kg/m2, female sex, cerebrovascular disease, cardiovascular disease, and SGOT > 40 U/L. CONCLUSIONS: Most of these risk factors represent end-stage processes and do not have good treatment alternatives. Perhaps one of the practical applications of these data is not to describe risk of proximal amputations but instead to look more closely at candidates who should be considered for distal procedures.     

Recent advances in infertility treatment

Infertility is defined as the inability to conceive after one year of regular coitus without contraception. Approximately 10% to 20% of childbearing-age couples are infertile in the United States. The demand for infertility investigations has increased dramatically in recent decades. The number of women using infertility services rose from 600,000 in 1968 to 1.35 million in 1988, an increase due, in part, to improved technology and increased publicity that began in the early 1980s. By 1995, the numbers were about 2.7 million. Recent advances in assisted reproductive technologies (ART) have provided greater possibilities for successful infertility treatment. Examples of new technologies include intracytoplasmic sperm injection, oocyte donation, and embryo cryopreservation.     

Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol

The effects of dietary cholesterol on brain amyloid precursor protein (APP) processing were examined using an APP gene-targeted mouse, genetically humanized in the amyloid beta-peptide (Abeta) domain and expressing the Swedish familial Alzheimer's disease mutations. These mice express endogenous levels of APP holoprotein and abundant human Abeta. Increased dietary cholesterol led to significant reductions in brain levels of secreted APP derivatives, including sAPPalpha, sAPPbeta, Abeta1-40, and Abeta1-42, while having little to no effect on cell-associated species, including full-length APP and the COOH-terminal APP processing derivatives. The changes in levels of sAPP and Abeta in brain all were negatively correlated with serum cholesterol levels and levels of serum and brain apoE. These results demonstrate that secreted APP processing derivatives and Abeta can be modulated in the brain of an animal by diet and provide evidence that cholesterol plays a role in the modulation of APP processing in vivo. APP gene-targeted mice lacking apoE, also have high serum cholesterol levels but do not show alterations in APP processing, suggesting that effects of cholesterol on APP processing require the presence of apoE.     

A biomechanical comparison of open and thoracoscopic anterior spinal release in a goat model

STUDY DESIGN: A biomechanical assessment of anterior release and discectomy in the thoracic spine was performed on an animal model using thoracoscopic and open thoracotomy techniques. OBJECTIVES: To compare the relative efficacy of these two techniques of release in achieving increased spinal mobility. BACKGROUND DATA: The clinical use of video-assisted thoracoscopy in the correction of spinal deformity is increasing. The effectiveness of thoracoscopic anterior spinal release with discectomy has not been evaluated biomechanically. METHODS: Anterior release with discectomy was performed on six midthoracic motion segments in five mature goats. The thoracoscopic technique was used for three levels on one side, and an open thoracotomy was used for the alternating three levels of the contralateral side. The duration of surgery for disc excision and the amount of blood loss for each technique were recorded. The intact cranial and caudal motion segments served as controls. The motion segments were individually subjected to nondestructive biomechanical testing. Torsional, sagittal, and coronal bending torques were applied, and the resulting angular displacement was measured. RESULTS: The duration of surgery to remove a disc thoracoscopically decreased as experience was gained by the surgeon. The amount of intraoperative blood loss was comparable using the two methods. There was significantly increased flexibility in the released segments with both techniques, compared with the flexibility in the intact levels for all three loading directions. There was no difference in the motion obtained after release between the two techniques. CONCLUSION: Open and thoracoscopic anterior release and discectomy have been demonstrated, through biomechanical in vitro testing, to increase the flexibility of the spine to a similar extent.     

Structural investigation of C4b-binding protein by molecular modeling: localization of putative binding sites

C4b-binding protein (C4BP) contributes to the regulation of the classical pathway of the complement system and plays an important role in blood coagulation. The main human C4BP isoform is composed of one beta-chain and seven alpha-chains essentially built from three and eight complement control protein (CCP) modules, respectively, followed by a nonrepeat carboxy-terminal region involved in polymerization of the chains. C4BP is known to interact with heparin, C4b, complement factor I, serum amyloid P component, streptococcal Arp and Sir proteins, and factor VIII/VIIIa via its alpha-chains and with protein S through its beta-chain. The principal aim of the present study was to localize regions of C4BP involved in the interaction with C4b, Arp, and heparin. For this purpose, a computer model of the 8 CCP modules of C4BP alpha-chain was constructed, taking into account data from previous electron microscopy (EM) studies. This structure was investigated in the context of known and/or new experimental data. Analysis of the alpha-chain model, together with monoclonal antibody studies and heparin binding experiments, suggests that a patch of positively charged residues, at the interface between the first and second CCP modules, plays an important role in the interaction between C4BP and C4b/Arp/Sir/heparin. Putative binding sites, secondary-structure prediction for the central core, and an overall reevaluation of the size of the C4BP molecule are also presented. An understanding of these intermolecular interactions should contribute to the rational design of potential therapeutic agents aiming at interfering specifically some of these protein-protein interactions.     

Catheter-free endoscopic laser ablation of the prostate using a 1-size prostatic stent

PURPOSE: Endoscopic laser ablation of the prostate is a safe alternative to transurethral prostatic resection. Recognized disadvantages include prolonged catheterization, postoperative discomfort and delayed symptomatic improvement. We assessed the role of a 1-size temporary prostatic stent in men undergoing endoscopic laser ablation of the prostate. MATERIALS AND METHODS: A total of 55 men a mean of 73 years old with outflow obstruction, including 9 who presented in urinary retention, underwent endoscopic laser ablation of the prostate and temporary stenting. Urinary flow rate, residual urine volume, symptom score and prostate specific antigen were measured preoperatively, and 6 weeks (with the stent in situ), 3 months (after stent removal) and 12 months postoperatively. Duration of hospital stay and complications were also recorded. RESULTS: Of the 55 men 37 (67%) voided immediately with the stent in situ, including 7 of the 9 in retention. At 6 weeks with the stent in place mean maximum urine flow was 17.3 ml. per second (preoperatively 8.7). Dysuria was reported by 3 patients. Stent related complications were rare. One stent migrated early, resulting in urinary retention, while 2 that migrated late were asymptomatic. No patient had acute urinary retention after stent removal. Maximum urinary flow rate measured at 6 weeks with the stent in situ was similar to that 1 year after endoscopic laser ablation of the prostate. CONCLUSIONS: The use of a 1-size, inexpensive plastic prostatic stent enabled catheter-free endoscopic laser ablation of the prostate in 67% of our patients. Early improvements in the urinary flow rate and a lower incidence of dysuria were additional benefits. The result of endoscopic laser ablation of the prostate at 1 year was comparable to that of transurethral prostatic resection.     

Dorsal capsulodesis using suture anchors

Scapholunate instability can be treated by stabilizing the scaphoid with the dorsal wrist capsule, which acts as a tether to control palmar rotation. We began using suture anchors instead of pull-out wires to secure the dorsal capsule to the scaphoid. Thirty-eight patients were treated with this method, and 35 were followed an average of 24 months. Sixteen were pain free, 12 had pain with activity, and 7 required additional surgical treatment. Patients regained 85% of expected grip strength, with 25 of the 35 returning to their preinjury job. The scapholunate gap, reduced at the time of surgery, recurred in 31 of the 35 patients, but this alone did not correlate with symptoms. This procedure improves symptoms in a majority of patients, but like other procedures described for scapholunate instability, it does not completely cure the problem.     

How to recognize and treat specific low back pain?

A wide variety of mechanical and non-mechanical disorders are associated with the clinical symptom of low back pain. Mechanical disorders are the cause of the vast majority of low back pain. Despite this frequency, the specific cause of mechanical low back pain can not be elucidated in spite of extensive diagnostic evaluation in a majority of individuals. Specific causes of low back pain are associated with less frequently occurring systemic illnesses including rheumatic, infectious, neoplastic, gynaecological and vascular disorders. The diagnostic process is more successful in identifying systemic disorders as the specific cause of low back pain. Non-surgical management is effective therapy with most patients with mechanical disorders of any form. Systemic illnesses require interventions directed specifically at healing the affected organ system.     

Analysis of the process of localization of fertilin to the sperm posterior head plasma membrane domain during sperm maturation in the epididymis

Fertilin is a heterodimeric (subunits alpha and beta) sperm plasma membrane protein. Both subunits belong to the ADAM protein family of surface proteins that contain a disintegrin and a metalloprotease domain. Fertilin functions in sperm-egg fusion by binding the sperm to the egg plasma membrane via a binding site in the disintegrin domain of fertilin beta. On testicular sperm of guinea pig, fertilin is distributed on the plasma membrane over the entire sperm head, but is found only on the posterior head once sperm have passed through the epididymis. This redistribution of fertilin to the posterior head can be partially mimicked in vitro if testicular sperm are briefly treated with trypsin. In this study we used immunofluorescence and digital image analysis to analyze how fertilin becomes restricted to the posterior head. We found that fertilin became restricted to the posterior head by migration of anterior head fertilin molecules into the posterior head domain. Comparison of immunofluorescence patterns and immunoblots of fertilin from seven regions of the epididymis showed a temporal correlation between the beginning of fertilin's migration to the posterior head and the proteolytic processing of the full-length fertilin beta precursor (the 85-kDa pro-beta form) to a 75-kDa intermediate, pro-beta*. Completion of the migration coincided with the further cleavage of pro-beta* to the 25- to 28-kDa mature form. Our data suggest that the cleavage of fertilin pro-beta to pro-beta* may initiate fertilin's migration into the posterior head domain and, after localization to that membrane domain, pro-beta* is cleaved to mature beta. We also report evidence that a common mechanism may be used to change the localization pattern of other sperm surface molecules. Other surface proteins were shown to become localized to either the posterior or the anterior head membrane domains on sperm at the same time fertilin became localized to the posterior head. These restrictions of surface protein localizations were also shown to immediately precede the development of the sperm's ability to swim and undergo the acrosome reaction, and thus redistribution of surface proteins may be necessary before sperm become functional.     

DARPP-32: regulator of the efficacy of dopaminergic neurotransmission

Dopaminergic neurons exert a major modulatory effect on the forebrain. Dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein (32 kilodaltons) (DARPP-32), which is enriched in all neurons that receive a dopaminergic input, is converted in response to dopamine into a potent protein phosphatase inhibitor. Mice generated to contain a targeted disruption of the DARPP-32 gene showed profound deficits in their molecular, electrophysiological, and behavioral responses to dopamine, drugs of abuse, and antipsychotic medication. The results show that DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission.