Biosynthesis of polyketides in heterologous hosts.

Polyketide natural products show great promise as medicinal agents. Typically the products of microbial secondary biosynthesis, polyketides are synthesized by an evolutionarily related but architecturally diverse family of multifunctional enzymes called polyketide synthases. A principal limitation for fundamental biochemical studies of these modular megasynthases, as well as for their applications in biotechnology, is the challenge associated with manipulating the natural microorganism that produces a polyketide of interest.

Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli.

The macrocyclic core of the antibiotic erythromycin, 6-deoxyerythronolide B (6dEB), is a complex natural product synthesized by the soil bacterium Saccharopolyspora erythraea through the action of a multifunctional polyketide synthase (PKS). The engineering potential of modular PKSs is hampered by the limited capabilities for molecular biological manipulation of organisms (principally actinomycetes) in which complex polyketides have thus far been produced. To address this problem, a derivative of Escherichia coli has been genetically engineered.

Intraoperative computerized tomography scanning to assess the adequacy of decompression in anterior cervical spine surgery.

Object: The purpose of this study was to improve the accuracy of bone removal during anterior spinal surgery. Intraoperative computerized tomography (CT) scanning was used to assess the success of bone resection and permit immediate correction in the event of inadequate bone removal.

Methods: The Phillips Tomoscan M was used to obtain preoperative cervical scans before and after cervical bone resection was complete.

Single Price/Case Price Purchasing in orthopaedic surgery: experience at the Lahey Clinic.

Background: Hospital revenues for orthopaedic operations are not keeping pace with inflation or with rising hospital expenses. In an attempt to reduce the hospital cost of orthopaedic operations by reducing the cost of operating-room supplies, we developed a Single Price/Case Price Purchasing Program for implants used in total hip arthroplasty, total knee arthroplasty, and total shoulder arthroplasty as well as for arthroscopic shavers and burrs, interference screws, and bone-suture anchors.

Methods: The Lahey Clinic asked orthopaedic vendors to supply all instruments, implants, and disposable items related to these selected products for one single price per unit or case.

PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer.

Objective: To assess the effectiveness of PC-SPES, a dietary supplement containing eight herbal extracts, which is a popular alternative therapy among patients with hormone-refractory prostate cancer; anecdotal reports claim that this agent provides relief of metastatic pain, improvements in quality of life and reduction of prostatic specific antigen (PSA) level.

Patients And Methods: Sixteen men treated for advanced metastatic prostate cancer (stage D3) with either orchidectomy or a luteinizing-hormone releasing hormone agonist, with or without anti-androgen, were enrolled into a prospective clinical trial to evaluate the possible toxic and beneficial effects of PC-SPES. After hormone-ablative therapy had failed, and with established disease progression, all patients received supplemental treatment with PC-SPES (2.

A multi-center study of intrathecal neostigmine for analgesia following vaginal hysterectomy.

Background: Intrathecal neostigmine injection produces analgesia in volunteers and reduces hypotension from intrathecal bupivacaine in animals. Initial clinical trials with neostigmine studied doses of more than 100 microg, but animal studies suggest that smaller doses may be effective. In addition, all controlled clinical trials of neostigmine have come from one Brazilian university.

Impact of a clinical pathway and implant standardization on total hip arthroplasty: a clinical and economic study of short-term patient outcome.

This study evaluates the impact of a clinical pathway (CP) and a hip implant standardization program (HISP) on the quality and cost of total hip arthroplasty (THA). Two hundred six unilateral THA operations for osteoarthritis were evaluated: 89 operations were performed in 1991 without a CP or HISP (4-year follow-up period); 117 operations were performed in 1993 with a CP and HISP (2-year follow-up period). All patients had good clinical results and excellent outcomes with short-term follow-up evaluation.

Knee implant standardization: an implant selection and cost reduction program.

The largest single unit cost in the hospital cost for total knee arthroplasty (TKA) is the cost of knee implants. We developed a knee implant standardization program to provide guidelines for knee implant selection and to reduce the cost of knee implants for hospitals. Patients are assigned to demand categories based on five criteria: age, weight, expected activity, general health, and bone stock.

Clinical outcome and survivorship analysis of core decompression for early osteonecrosis of the femoral head.

Thirty-three hips in 23 patients (followed for 5.3 years) were treated with core decompression for early osteonecrosis of the femoral head (Ficat and Arlet I, IIA, IIB). When the clinical endpoint of severe pain was used for survivorship, 76% of hips survived 1 year, 52% survived 2 years, and 44% survived 5 years.

Advanced practice roles for nurses in tomorrow's healthcare systems.

Advanced practice nurses (APNs) have traditionally been a diverse group in terms of titles, education, credentials, and roles. The classification of APN usually encompasses the nurse practitioner (NP), certified nurse midwife (CNM), certified registered nurse anesthetist (CRNA), and clinical nurse specialist (CNS). NP, CRNA, and CNM roles have been more clearly delineated than the CNS roles.

Case report: radiation prevention of heterotopic ossification after bone and joint surgery in sites other than hips.

Five patients were given single dose irradiation in an attempt to prevent heterotopic ossification after bone and joint surgery in sites other than hips. All patients were at risk for the development of post-operative heterotopic ossification. Two patients were treated with 6 Gy and three patients were treated with 7 Gy the day after operation.

Implant standardization for total hip arthroplasty. An implant selection and a cost reduction program.

Total hip arthroplasty (THA) has been targeted by the United States federal government for cost control because of its high cost and rising incidence in the aging population. The hospital cost for THA during the 1980s was controlled by utilization review and a reduction in the volume of services delivered for each THA. The single largest increase in the cost of THA during the 1980s was the cost of hip implants.

Single-dose irradiation for the prevention of heterotopic ossification after total hip arthroplasty. A comparison of doses of five hundred and fifty and seven hundred centigray.

One hundred and seven hips (ninety-four patients) that had risk factors associated with the development of heterotopic ossification after total hip arthroplasty were treated with a single dose of radiation after the operation in an attempt to prevent the formation of heterotopic bone. A study was conducted to compare the efficacy of a single dose of 550 centigray (nineteen hips) with that of a single dose of 700 centigray (eighty-eight hips). Heterotopic ossification developed in twelve (63 per cent) of the nineteen hips that were treated with 550 centigray; grades 1, 2, and 3, according to the classification of Brooker et al.

Repair of injured vertebral artery in anterior cervical procedures.

Study Design: A case report of treatment of injury to the vertebral artery in anterior cervical procedures is presented with a review of the literature.

Objectives: The feasibility of direct surgical repair is suggested.

Summary Of Background Data: Currently, ligation or tamponade is accepted as the treatment of injury to the vertebral artery in anterior cervical surgery.

Repair of failed transpedicle screw fixation. A biomechanical study comparing polymethylmethacrylate, milled bone, and matchstick bone reconstruction.

In a random, controlled laboratory study, pedicle screws placed in human cadaveric vertebrae were axially loaded to failure. Three repair methods were tested. Use of low pressure polymethylmethacrylate yielded 149% of the original pullout strength, milled bone yielded 70% of the initial pullout strength, and matchstick bone yielded 56% of the initial pullout strength.

Evaluation of autologous shed blood for autotransfusion after orthopaedic surgery.

Autologous shed blood for autotransfusion was evaluated at four medical centers in a prospective randomized study. One hundred twenty-eight patients were studied after hip replacement, knee replacement, or spine fusion. The efficacy of autologous shed blood in reducing homologous transfusion was evaluated.

Cold compressive dressing after total knee arthroplasty.

The efficacy of a cold compressive dressing after total knee arthroplasty (TKA) was prospectively studied in 105 knees in 76 patients. All components were cemented. All patients were placed in continuous passive motion machines after operation.

Burst fractures of the fifth lumbar vertebra.

Eleven patients with burst fractures of the fifth lumbar vertebra were reviewed. The results of nonoperative treatment were compared with that of immediate surgery and stabilization with pedicle screw fixation. Five patients were treated nonoperatively and six patients underwent pedicle screw instrumentation and spinal fusion.

Methylmethacrylate monomer and fat content in shed blood after total joint arthroplasty.

Twenty-five patients were prospectively evaluated to quantify levels of methylmethacrylate monomer and fat in systemic blood and in shed blood after total joint arthroplasty. Levels of methylmethacrylate monomer in systemic blood were measured at intervals after insertion of the prosthesis. Levels of methylmethacrylate monomer in shed blood were measured at intervals after insertion of the drain.

Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog.

The continuous spinal administration of baclofen has been shown to have therapeutic benefit in the management of spasticity in humans with neuraxial injuries. The present study systematically investigated the potential spinal neurotoxicity of continuous intrathecally-infused baclofen in dogs. Male beagle dogs were prepared with chronic lumbar intrathecal catheters connected to subcutaneously implanted infusion pumps.

Is a serotonergic mechanism involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced appetite suppression in the Sprague-Dawley rat?

The major cause of TCDD-induced death in rats is a progressive voluntary feed refusal which has been correlated with reduced gluconeogenesis. Since centrally administered TCDD does not cause death or decreased feed intake in rats, the ability of TCDD to suppress appetite via peripheral mechanisms acting on the central nervous system was examined in two experimental models. First, it was found that the feed intake of rats on scheduled feeding cycles was not decreased by blood transfused from rats with TCDD-induced appetite suppression (8 days after a lethal dose of TCDD, i.

Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty.

Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis.

[Methodology and diagnostic possibilities of macro-EMG. II. Diagnostic possibilities].

The macro-EMG can be recorded with a modified single fiber or concentric needle. The two needles attain different results with smaller potentials values for the concentric needle type. For the single fiber type normal data are given for the EDC and tibialis anterior muscle.

Relationship between electrical and mechanical properties of motor units.

In six healthy volunteers, the size of the motor unit action potential (MUAP) was related to its contractile behaviour. Electrical activity was determined by measuring amplitude and area of the potential, using the macro electromyography (EMG) technique. The mechanical response was characterised by contraction time, twitch force and relaxation time, recorded with the spike triggered averaging technique.

[Methodology and diagnostic potentialities of macro-EMG. I. Methodology].

Macro-EMG records electrical activity from the whole motor unit (MU) as a parameter of its size. The main component of the recording device is a modified single fiber or concentric needle electrode. Different sized uptake areas allow to record with different selectivities from the MU.