Nonoperative treatment of an interosseous ganglion cyst.

Ganglion cysts of the knee are being reported more frequently secondary to an increased rate of magnetic resonance imaging studies. Although knee pain is the impetus for imaging, ganglion cysts are often incidental findings. Nonoperative treatment is a successful therapeutic option. We report a patient with variable pain presentations over the course of her treatment. The pattern of complaints pointed to different primary etiologies about the knee, but all were common to an interosseous ganglion cyst. A stepwise assessment and expansion of the differential diagnosis allowed for appropriate utilization of modalities and limited morbidity with nonoperative therapy.

Scapular instability. The scapulothoracic joint.

Scapular instability may be the result of a variety of casues of which the clinician should be made aware. Work-up should include an initial radiographic evaluation and may require more in-depth investigation. Treatment should be prescribed dependent on the underlying diagnosis. In most cases, instability about the scapula can be treated with a careful plan of exercises to strengthen the involved musculature. It may take upwards of 12 to 18 months to achieve adequate results. Nonoperative failures may need to be treated with surgical techniques including nerve dissection and reconstruction with muscle flaps.

Therapeutic options in the treatment of clozapine-induced sialorrhea.

Clozapine is an effective atypical antipsychotic drug, but its use may be compromised by its side effects. Agranulocytosis may be fatal, but sialorrhea occurs more frequently and plays a major role in patients' noncompliance. A MEDLINE search from 1975-2000 revealed that treatment of clozapine-induced sialorrhea is predominantly based on case reports. Due to its elusive mechanism, physicians have attempted to treat this side effect with agents that counteract clozapine's adrenergic and muscarinic properties. We evaluated reported treatment options and other possible strategies from a pharmacologic standpoint. Antimuscarinic agents and alpha-receptor agonists are both viable options but must be administered and monitored cautiously in patients with psychiatric disorders. Although not yet available in the United States, pirenzepine, a selective muscarinic receptor antagonist, has the most promising mechanism. Other selective, peripherally acting agents must be investigated in controlled clinical trials to determine their efficacy as possible alternatives.

Therapeutic selective nerve root block in the nonsurgical treatment of atraumatic cervical spondylotic radicular pain: a retrospective analysis with independent clinical review.

OBJECTIVE: To investigate the outcomes resulting from the use of fluoroscopically guided therapeutic selective nerve root block (SNRB) in the nonsurgical treatment of atraumatic cervical spondylotic radicular pain. STUDY DESIGN: Retrospective study with independent clinical review. PARTICIPANTS: Twenty subjects (10 men, 10 women) with mean age 56.6 years. METHODS: Each patient met specific physical examination, radiographic, and electrodiagnostic criteria to confirm a level of cervical involvement. Those patients whose root level remained indeterminate were required to demonstrate a positive response to a fluoroscopically guided diagnostic SNRB prior to the initiation of treatment. Therapeutic injections were administered in conjunction with physical therapy. Data collection and analysis were performed by an independent clinical reviewer. MAIN OUTCOME MEASURES: Pain score, work status, medication usage, and patient satisfaction. RESULTS: Twenty patients with an average symptom duration of 5.8 months were included. An average of 2.2 therapeutic injections was administered. Follow-up data collection transpired at an average of 21.2 months following discharge from treatment. A significant reduction (p = .001) in pain score was observed at the time of follow-up. Medication usage was also significantly improved (p = .005) at the time of follow-up. An overall good or excellent result was observed in 60%. Thirty percent of patients required surgery. Younger patients were more likely (p = .0047) to report the highest patient satisfaction rating following treatment. CONCLUSIONS: This study suggests that fluoroscopically guided therapeutic SNRB is a clinically effective intervention in the treatment of atraumatic cervical spondylotic radicular pain.

Phospholipid transfer proteins and physiological functions.

Issues of how cells generate and maintain unique lipid compositions in distinct intracellular membrane systems remain the subject of much study. A ubiquitous class of soluble proteins capable of transporting phospholipid monomers from membrane to membrane across an aqueous milieu has been thought to define part of the mechanism by which lipids are sorted in cells. Progress in the study of these phospholipid transfer proteins (PLTPs) raises questions regarding their physiological functions in cells and the mechanisms by which these proteins execute them. It is now clear that across the eukaryotic kingdom, members of this protein family exert essential roles in the regulation of phospholipid metabolism and central aspects of phospholipid-mediated signaling. Indeed, it is now known that dysfunction of specific PLTPs defines the basis of inherited diseases in mammals, and this list is expected to grow. Phospholipid transfer proteins, their biochemical properties, and the emerging clues regarding their physiological functions are reviewed.

An unusual extraspinal cause of bilateral leg pain.

Low back pain with pain radiating to the lower extremities is common in patients referred to a spine center. Lumbar spine pathology is commonly the etiology of such symptoms, but extraspinal causes of back and leg pain can manifest as a radicular disorder. Extraspinal etiologies must be considered in the workup of back and leg pain. This report describes an unusual case of spontaneously occurring bilateral femoral neck stress fractures presenting as low back pain with seemingly bilateral L4 radicular symptoms.

The lipid-free structure of apolipoprotein A-I: effects of amino-terminal deletions.

Deletion mutants of human apolipoprotein A-I (apo hA-I) have been produced from a bacterial expression system to explore the function of the specific domains comprising residues 1-43, 1-65, 88-98, and 187-243, respectively, in the lipid-free conformation and in the lipid-binding mechanism of apo hA-I. Initial studies on apo Delta(1-43)A-I and apo Delta(187-243)A-I have already been reported. To aid purification of these mutants, a histidine-containing N-terminal extension was incorporated (+his); in cases where comparison with the (-his) construct was possible, little effect on the physical properties due to the (+his) extension was found. All mutants have folded structures in their lipid-free state, however these structures differ widely in their relative thermodynamic stability and extent of secondary structure. The mutant with the fewest residues deleted, apo Delta(88-98)A-I(+his), has the least secondary structure (only 34% helix) and is also the least stable (DeltaG = 2.9 kcal/mol). Determined from sedimentation velocity measurements on the lipid-free proteins, all but apo Delta(1-65)A-I(+his) exhibited a range of conformers in solution, which fluctuated around a highly elongated species (dimensions equal to approximately (14-16) x approximately 2.3 nm). Apo Delta(1-65)A-I(+his) exhibited a discrete species which was less asymmetric (dimensions equal to 9 x 2.9 nm). Apo Delta(88-98)A-I(+his) showed extreme heterogeneity with no predominating conformer. Spectroscopic studies (ANS binding and circular dichroism) indicate that there is little difference in the lipid-free structure of the carboxy-terminal deletion mutant, apo Delta(187-243)A-I(+/-his) compared to wild-type (wt) apo wtA-I(+/-his), but substantial differences are observed between wt and the amino-terminal deletion mutants, apo Delta(1-43)A-I, apo Delta(1-65)A-I(+his), and apo Delta(88-98)A-I(+his). In contrast, the lipid-binding properties are impaired for apo Delta(187-243)A-I(+/-his), as measured by dimyristoyl phosphatidylcholine (DMPC) liposome turbidity clearance kinetics and palmitoyloleoyl phosphatidylcholine (POPC) equilibrium binding. Apo Delta(1-43)A-I, apo Delta(1-65)A-I(+his), and apo Delta(88-98)A-I(+his) show lipid affinities statistically similar to apo wtA-I(+his), but significantly defective DMPC clearance kinetics. Interestingly, lecithin:cholesterol acyltransferase (LCAT) activation results correlate qualitatively with the lipid-binding affinity for all mutants but apo Delta(88-98)A-I(+his), suggesting that this mutant has an altered and possibly noncooperative lipid-bound structure as well as an altered lipid-free structure. These results suggest helix 1 (residues 44-65) and helix 10 (residues 220-240) are both required for native lipid-binding properties, while the presence of internal residues, at least helix 3 (residues 88-98), is essential for proper folding of both the lipid-free and lipid-bound conformations. Importantly, studies on apo Delta(88-98)A-I(+his) provide the first experimental evidence that a native-like structure is not necessary for native-like lipid affinity, but apparently is necessary for both DMPC solubilization and LCAT activation. These results provide support for a hypothetical, multistep structure-based mechanism for apo hA-I lipid binding.

Comparison of serologic and protective responses induced by two Pasteurella vaccines.

Vaccine development for the prevention of pneumonic pasteurellosis remains a critical issue for the feedlot industry. Most currently available Pasteurella vaccines are formulated to stimulate immunity by either providing an adequate antigenic mass in the administered dose, or by relying on subsequent production of antigens by in vivo growth of live organisms. The ability of these different types of vaccines to stimulate rapid and high titres to key antigens is a key factor that will influence subsequent resistance to disease. The serologic and protective responses to a streptomycin-dependent, modified-live vaccine and a killed (bacterin-toxoid) vaccine against experimental pneumonic pasteurellosis were compared. Calves were vaccinated with a single injection of either a test vaccine or phosphate-buffered saline, challenged 14 d later by transthoracic injection with Pasteurella haemolytica, and euthanized 3 d post-challenge to evaluate the severity of pneumonia. On days 0, 7, and 14, serologic responses to various P. haemolytica antigens, including cell-associated and soluble antigens, were determined by enzyme-linked immunosorbent assays, and anti-leukotoxin antibody levels were determined by leukotoxin neutralization. The bacterin-toxoid elicited significantly greater serologic responses compared to controls for all antigens. The modified-live vaccine elicited a significantly greater response compared to controls for a whole-cell antigen preparation. Lesion scores were significantly smaller (greater protection) in calves that received the bacterin-toxoid, but not the modified-live vaccine, compared to controls.

Structural analysis of apolipoprotein A-I: effects of amino- and carboxy-terminal deletions on the lipid-free structure.

An amino-terminal deletion mutant (residues 1-43) and a carboxy-terminal deletion mutant (residues 187-243) of human apoliprotein A-I (apo hA-I) have been produced from a bacterial expression system to explore the importance of the missing residues for the conformation of apo hA-I. Our focus has been to study the lipid-free structure of apo hA-I to understand how discrete domains influence the conformational plasticity of the protein and, by inference, the mechanism of lipid binding. All spectral and physical measurements indicate that both apo delta(1-43)A-I and apo delta(187-243)A-I have folded, tertiary structures. These structures differ in the specific arrangement of helical domains based, in part, on their relative thermodynamic stability, near- and far-UV CD, limited proteolysis, and the accessibility of tryptophans to fluorescence quenchers. In addition, all data indicate that the folded domains of apo hA-I and apo delta(187-243)A-I are very similar. Results from analytical ultracentrifugation suggest that lipid-free apo hA-I and the deletion mutants each exist in a dynamic equilibrium between a loosely folded, helical bundle and an elongated monomeric helical hairpin. The conformational heterogeneity is consistent with significant ANS binding exhibited by all three proteins and could help to explain the facile lipid binding properties of apo hA-I.

Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation.

The structure of truncated human apolipoprotein A-I (apo A-I), the major protein component of high density lipoprotein, has been determined at 4-A resolution. The crystals comprise residues 44-243 (exon 4) of apo A-I, a fragment that binds to lipid similarly to intact apo A-I and that retains the lipid-bound conformation even in the absence of lipid. The molecule consists almost entirely of a pseudo-continuous, amphipathic alpha-helix that is punctuated by kinks at regularly spaced proline residues; it adopts a shape similar to a horseshoe of dimensions 125 x 80 x 40 A. Four molecules in the asymmetric unit associate via their hydrophobic faces to form an antiparallel four-helix bundle with an elliptical ring shape. Based on this structure, we propose a model for the structure of apo A-I bound to high density lipoprotein.

Truncation of the amino terminus of human apolipoprotein A-I substantially alters only the lipid-free conformation.

An amino-terminal deletion mutant (residues 1-43) of human apolipoprotein A-I (apo hA-I) has been produced from a bacterial expression system to explore the structural and functional role of these amino acids, encoded by exon 3, in apo hA-I. Lipid binding of apo delta (1-43)A-I and lipid binding of apo hA-I are very similar as assessed by surface activity, lipid association with palmitoyloleoylphosphatidylcholine (POPC) vesicles, and lipid association with plasma lipoproteins. Preliminary kinetic measurements appear to show that the reactivity of lecithin:cholesterol acyltransferase (LCAT) with the mutant is slightly decreased compared to wild-type apo hA-I. Collectively, these results indicate that the N-terminal region is not necessary for lipid binding or activation of LCAT. In contrast, there are significant structural differences between lipid-free apo delta (1-43)A-I and apo hA-I, as judged by denaturant-induced unfolding, binding of the fluorescent probe 1-anilinonaphthalene-8-sulfonate, surface balance measurements, and far- and near-ultraviolet circular dichroic spectroscopy. All spectral and physical measurements indicate apo delta (1-43)A-I has a folded, tertiary structure, although it is significantly less stable than that of apo hA-I. It is concluded that the N-terminal 43 residues are an important structural element of the lipid-free conformational state of apo hA-I, the absence of which induces a fundamentally different fold for the remaining carboxy-terminal residues, compared to those in native apo hA-I.

Comparative evaluation of two surgical scrub preparations in cattle.

One hundred seventeen cattle that had undergone surgery were assigned randomly to two preoperative skin preparation protocols. Group 1 (60 animals) skin preparation was with povidoneiodine soap and isopropyl alcohol, whereas group 2 (57 animals) had skin preparation with chlorhexidine gluconate and isopropyl alcohol. Quantitative microbial culture plates were used to estimate the number of colony forming units (CFUs) before skin preparation (prescrub), after skin preparation (postscrub), after surgery (postoperative), and in room air (environment). A significant decrease in CFU occurred postscrub for both skin preparations (P < .05). Chlorhexidine and alcohol preparation resulted in significantly fewer CFUs (LSMean +/- SE = 2.79 CFU +/- 1.74) and a greater percentage reduction in CFUs (98.64% +/- 2.01) postscrub than providone and alcohol (LSMean +/- SE = 10.27 CFUs +/- 1.51, 93.29% +/- 1.85); (P < .005). Group 2 had a significantly higher frequency of negative cultures postscrub (49.1%) compared with group 1 (18.3%) (P < .001). The number of postoperative CFUs were not significantly different between the two treatment groups. Wound infection frequency for clean surgical procedures was not significantly different between the two skin preparation protocols (group 1 = 9.8%, group 2 = 10.7%), however, infection frequency was significantly higher for surgical procedures with a ventral abdominal approach (5 of 14, 35.7%,) compared with a flank approach (1 of 41, 2.4%) or other approaches (orthopedic procedures) (1 of 16, 6.3%) (P < .05). Both skin preparation protocols were effective and safe in decreasing the skin microflora population of cattle before surgery and although preparation with chlorhexidine gluconate and alcohol resulted in less CFUs immediately postscrub, the frequency of surgical wound infection was similar for both protocols.

Conjunctival microbial flora of clinically normal pigs.

Conjunctival swab specimens from healthy pigs were cultured to determine normal microbial population. Four commercial swine operations were selected for study. Pigs of 4 age groups were tested: nursing pigs, nursery pigs, feeder pigs, and sows. Swab specimens were taken from the conjunctival sac of each pig. Bacterial, fungal, and mycoplasmal growth was determined separately. Chlamydia sp was detected by use of an ELISA. Bacteria were recovered from 98% of specimens evaluated. alpha-Streptococcus sp (89%) was the most commonly recovered organism, followed by Staphylococcus epidermidis (39%) and Staphylococcus sp (39%). Mycoplasma sp was not detected in any of the specimens. Chlamydia sp was identified in 28% of all specimens evaluated. These results are similar to reports of normal conjunctival flora in other domestic animals.