Ulnar fractures with bisphosphonate therapy: a systematic review of published case reports.

SUMMARY: A systematic review of eight ulnar fractures in seven patients with bisphosphonate therapy was performed to describe the characteristics and predisposing factors. The proximal ulna is likely to be fractured, especially in the dominant limb of elderly female patients using walking aids after 7 to 15 years of bisphosphonate use. INTRODUCTION: Long-term bisphosphonate use has been suggested to result in decreased bone remodelling and increased risk of atypical fractures. While the relationship between bisphosphonate use and atypical femoral fractures has been extensively studied, there is relative rarity and unawareness of these fractures in the forearm. We conducted a systematic review of existing case reports to better describe the characteristics and predisposing factors for fractures occurring in patients with bisphosphonate therapy. METHODS: The systematic review was conducted according to PRISMA guidelines. All studies with ulnar fractures in individuals with history of bisphosphonate use were included, with data extracted and analysed in totality. RESULTS: Seven patients with eight fractures are included. Predisposing factors include elderly females requiring walking aids. There is a propensity for the proximal ulna to be fractured, especially in the dominant limb used for ambulation or transfer. All patients were on bisphosphonate for 7 to 15 years. All fractures were atraumatic, non-comminuted, transverse in configuration, had localised periosteal or endosteal thickening at the fracture site and generalised cortical thickening of the diaphysis. CONCLUSION: Ulnar fractures in patients with bisphosphonate therapy demonstrate features similar to those described for atypical femoral fractures, suggesting that these fractures could also possibly be due to bisphosphonate use. However, the ulna appears to be able to tolerate longer periods of alendronate use prior to fracture development. The mechanism and characteristics of these fractures additionally suggest the presence of repetitive stress that accumulates over time due to suppressed bone remodelling in patients on bisphosphonates, eventually resulting in these fractures.

Widely tunable LP11 cladding-mode resonance in a twisted mechanically induced long-period fiber grating.

A record tunability of 35 nm for the LP(11) cladding-mode resonance in a twisted mechanically induced long-period fiber grating using standard single-mode communication fiber is demonstrated. By forming the LP(11) resonance far away from its cut-off wavelength and modifying the grooves of the grating in the form of smooth semicircular humps, a high twist sensitivity of 8.75 nm/(rad/cm) and a controlled tunability of 35 nm is achieved. The fiber with its lacquer coating is not broken even at a severe twist rate of 5.44 rad/cm. The present design can be used as a novel variable optical selective wavelength attenuator since the bandwidth, rejection efficiency, and center wavelength can be controlled by changing the grating length, pressure over the grating, and fiber twist, respectively. Using the results, a cost-effective tunable variable optical attenuator for selective channel-blanking applications is also demonstrated. A fine tunability of 1.5 nm is achieved for a twist rate change of 0.1 rad/cm.

Paradoxical motion in L5-S1 adult spondylolytic spondylolisthesis.

INTRODUCTION: In patients with spondylolisthesis, it is assumed that flexion accentuates anterior displacement, whereas extension causes some reduction. Paradoxical movement-where flexion causes reduction of spondylolisthesis and extension increases the anterior translation, is rarely described. In this study, we investigate the prevalence of paradoxical motion in patients with L5-S1 spondylolytic spondylolisthesis and why this abnormal motion occurs. MATERIALS AND METHODS: Flexion and extension radiographs of 41 patients with grade I and II spondylolytic spondylolisthesis of the L5-S1 segment were analysed. Patients who had previous lumbar spine surgery, recent lumbar spine trauma, those more than 50 years of age and those with poor quality radiographs were excluded. RESULTS: There were 24 male and 17 female patients. The average age was 32.7 years. Of the 41 patients, 29 (70.7%) showed no significant instability. Six (15%) patients showed anterolisthesis, where flexion accentuated the forward displacement, while further six (15%) patients showed paradoxical motion. Statistical analyses found that patients with paradoxical motion had a significantly higher slip angle. CONCLUSION: In this study, we have demonstrated that: (1) paradoxical motion in spondylolytic spondylolisthesis is more common than previously thought. (2) Patients without anterolisthesis during flexion in dynamic radiographs may still have (paradoxical) instability. (3) Paradoxical motion may be more common in patients with a low sacral slope and increased lumbosacral lordosis.

Neuroanatomical basis for the tarsal tunnel syndrome.

BACKGROUND: The results of surgical treatment for tarsal tunnel syndrome have been suboptimal, especially in the absence of space-occupying lesions. We attribute this to a poor understanding of the detailed anatomy of the `tarsal tunnel' and potential sites of nerve compression. METHODS: This study involved the dissection of 19 cadaveric feet. All findings and measurements were documented with digital photography and digital calipers. RESULTS: This study demonstrated three well-defined, tough fascial septae in the sole of the foot. In addition to the flexor retinaculum and the abductor hallucis, two of these septae represented potential sites of compression of the posterior tibial nerve and its branches. The medial plantar nerve may be entrapped under the medial septum. However, in 16 of 19 feet, the medial plantar nerve did not traverse beneath the septum. The lateral plantar nerve traversed beneath the medial septum in all specimens. The nerve to abductor digiti minimi may be trapped under the medial and intermediate septum. CONCLUSION: We detailed the anatomical relationship of the nerve branches relative to the fibrous septae and found that the medial plantar nerve did not traverse a septae in all specimens. CLINICAL RELEVANCE: We believe better understanding of the anatomical relationships of the tarsal tunnel and a clear communication system among anatomists, neuroradiologists and foot and ankle surgeons will facilitate accurate preoperative localization of the site of nerve compression possibly leading to better outcomes.

Percutaneous distal clavicle excision for acromioclavicular joint arthritis: our experience and early results of a novel surgical technique.

PURPOSE: Symptomatic acromioclavicular joint (ACJ) osteoarthritis causes pain and limitations in activities of daily living. Open and arthroscopic distal clavicle excision techniques have been described with good outcomes. However, both techniques have their own sets of advantages and disadvantages. This study describes a novel technique of percutaneous distal clavicle excision for symptomatic ACJ osteoarthritis and our two-year results. METHODS: Fifteen consecutive patients underwent percutaneous distal clavicle excision for ACJ arthritis. These patients had failed a trial of conservative treatment. The ACJ was confirmed as the pain generator with an intraarticular steroid/lignocaine injection, and shoulder MRI was used to exclude alternative pain generators in the shoulder. They had a minimum of two years of follow-up. RESULTS: At a mean of 26.8 months postoperatively, the mean VAS pain score was 0, and the mean Constant score for the shoulder was 87.3 points (range 50-94), which corresponded to 1 good, 1 very good and 13 excellent results. The mean SF-36 score was 94.9 points (range 65-100). There were statistically significant improvements in the VAS scores, Constant shoulder scores and SF-36 scores at one year and two years of follow-up (p < 0.05). Three unique complications, namely subcutaneous emphysema, "missing" of the distal clavicle and thermal skin injury, were encountered. Our surgical technique has since been modified to circumvent these complications. CONCLUSION: Our novel technique of percutaneous distal clavicle excision yields a 93.3% good-to-excellent results based on the Constant shoulder score and durable pain relief based on VAS at two years.

Plasma proteinase inhibitory activity in ectopic and molar pregnancy.

Antitryptic, antichymotryptic and alpha 2- macroglobulin activities were measured in sera of normal nonpregnant and normal pregnant women and women with tubal ectopic pregnancy and molar pregnancies in the first 5 to 7 weeks of pregnancy calculated from the last menstrual period. While alpha 2-macroglobulin decreased in early normal pregnancy compared to nonpregnant state (p<0.001), in ectopic and molar pregnancies there was an increase in alpha 2- macroglobulin activity (p < 0.001), as compared to nonpregnant and normal pregnant women. Antitryptic activity did not increase in normal and ectopic pregnancy, however was increased in molar pregnancy (p < 0.01). Antichymotryptic activities did not show a change either in normal pregnancy or in cases of ectopic and molar pregnancy. Drop in alpha 2- macroglobulin activity to near normal levels in ectopic, 6 weeks post surgery, correlated well with the decrease in ß-hCG. However, in molar pregnancy, alpha 2- macroglobulin remained elevated even when the ß-hCG levels in serum returned to zero 10 weeks after surgery. The studies suggest a major role for circulating proteinase inhibitors especially alpha 2-macroglobulin in regulating proteinase activity in normal, ectopic and molar pregnancy.

Management of the floating shoulder: Does the glenopolar angle influence outcomes? A systematic review.

INTRODUCTION: Currently there is no consensus on the optimal treatment of the "floating shoulder". We aim to perform a systematic review to determine outcomes in the management of this condition. MATERIALS AND METHODS: Studies related to the management of the "floating shoulder" were identified by a review of medline using platform Pubmed/Ovid, Scopus and Cochrane library data bases. Studies were included if they: (1) are published in the English language and (2) reported outcomes of at least 2 or more cases of floating shoulder injuries using at least one objective shoulder scoring system. Exclusion criteria were (1) non-human and biomechanical studies and (2) studies with a clear selection bias. Three treatment groups were identified. Group 1-non-operative, Group 2-fixation of clavicle only, and Group 3-fixation of clavicle and scapula neck. RESULTS: Thirteen studies gave a population of 244 subjects of which 104 had non-operative treatment, 98 had internal fixation of the clavicle only and 42 had fixation of both the clavicle and the scapula. There were no differences in the outcome scores among the 3 treatment arms as the patients with undisplaced or minimally displaced fractures had conservative treatment and those with displaced fractures were surgically stabilised. There was a positive correlation between the final glenopolar angle and the Constant score. CONCLUSIONS: The review was unable to show a difference in outcomes among the 3 treatment groups. Any treatment modality that restores the glenopolar angle is likely to result in a good outcome. LEVEL OF EVIDENCE: Therapeutic level IV.

Upper Extremity Innervation Patterns and Clinical Implications for Nerve and Tendon Transfer.

BACKGROUND: The authors previously studied the intramuscular innervation of 150 upper limb muscles and demonstrated that certain patterns of intramuscular innervation allowed muscles to be split into compartments with independent function. This study aims to determine the location, extramuscular course, and number of motor nerve branches of upper limb peripheral nerves. The authors want to combine this information with their previous work to create a blueprint of upper limb neuromuscular anatomy that would be useful in reconstructive surgery. METHODS: Ten fresh frozen cadaveric upper limbs were dissected. The origin of branches from the peripheral nerve trunk, their course, and the number of motor nerves per muscle were determined. The authors reviewed all the images of the Sihler-stained muscles from their earlier study. RESULTS: Motor nerve branches arise at the intersection of nerve trunk and muscle belly and are clustered near the origin of muscle groups. Two patterns of extramuscular innervation were noted, with one group having a single motor nerve and another group with consistently more than one motor nerve. A modified classification of muscles was proposed based on the orientation of muscle fibers to the long axis of the limb, the number of muscle compartments, and the number of heads of origin or the tendons of insertion. CONCLUSIONS: Motor nerve clusters can be located based on fixed anatomical landmarks. Muscles with multiple motor nerves have morphology that allows them to be split into individual compartments. The authors created a muscle and nerve blueprint that helps in planning nerve and split muscle transfers.

The course of the inferior gluteal nerve in the posterior approach to the hip.

We investigated the relationship of the inferior gluteal nerve to gluteus maximus by dissecting the muscle in 12 fresh-frozen and formalin-treated cadavers. The anatomy was recorded using still digital photography. The course of the inferior gluteal nerve was carefully traced and was noted to enter the deep surface of gluteus maximus approximately 5 cm from the tip of the greater trochanter of the femur. The susceptibility of the nerve to injury during a posterior approach to the hip may be explained by its close relationship to the deep surface of gluteus maximus. It is easily damaged before it has been seen if the muscle is split and parted more than 5 cm from the tip of the greater trochanter of the femur. We suggest that a modified posterior approach be used to expose the hip to avoid damage to this nerve.

Deep branch of the radial nerve in lateral surgical approaches to the radial head - A cadaveric study.

INTRODUCTION: The traditional Kocher approach for lateral radial head exposure may be complicated by injury to the deep branch of the radial nerve (DBRN) and the radial collateral ligament. Kaplan approach is less commonly used, due to its known proximity to the DBRN. Extensor Digitorum Communis (EDC) splitting approach allows possible wide surgical exposure and low risk of radial collateral ligament injury. The comparison of the proximity of the DBRN to the surgical dissection at the level of radial head among approaches to the radial head has not previously been evaluated. We aimed to determine the anatomical proximity of the DBRN in these 3 common radial head approaches and to define a safe zone of dissection for the surgical exposure. METHODS: Cadaveric dissections of 9 pairs of fresh frozen upper extremities were performed using EDC splitting, Kaplan and Kocher approach to the radial head sequentially in a randomized order. A mark was made on the radial head upon initial exposure during dissection. Measurements from the marked point of the radial head to the DBRN were made at the level of radial head. RESULTS: The distance of DBRN to the radial head was 20 (17-22) mm in EDC splitting approach, 7 (3-11) mm in Kaplan approach and 29 (25-33) mm in Kocher approach. The EDC splitting approach was associated with a significantly lower chance of encountering the DBRN at the level of radial head as compared to the Kaplan approach (P<0.001). In all cases, lateral ligamentous complex was not exposed in Kaplan and EDC approaches, but were encountered in Kocher approach, risking injury to the radial collateral ligament. CONCLUSIONS: The EDC splitting approach provides adequate exposure without the need to elevate or retract the EDC and ECU muscle mass that could risk injuring the DBRN. The Kaplan approach should be done by experienced surgeons who are familiar with the anatomy in this region, with extreme caution due to proximity of the DBRN to the surgical dissection at the level of the radial head. Caution of the DBRN should be taken during anterior elevation and retraction of the muscle mass in Kocher approach. LEVEL OF EVIDENCE: IV.

Cloning of the triosephosphate isomerase gene of Plasmodium falciparum and expression in Escherichia coli.

A major supply of energy in the rapidly multiplying intraerythrocytic Plasmodium falciparum is from the glycolytic pathway. We have isolated the cDNA and genomic clones of the glycolytic enzyme, triosephosphate isomerase (TPI) by polymerase chain reaction (PCR). Degenerate oligonucleotides obtained by reverse translation of conserved polypeptide sequences derived from TPIs of other organisms, were used to prime PCR on P. falciparum DNA. The P. falciparum TPI gene is interrupted by a single intron which divides the coding region into two exons. The coding region encodes a protein of 248 amino acids which is of the same size as TPIs from other organisms and shares 42-45% homology with other known eukaryotic TPIs. On comparison with human TPI the catalytic domain was found to be highly conserved, while significant variations occurred at the other regions in the protein sequence. The P. falciparum TPI gene was cloned into the expression vector pTrc99A and hyperexpressed as an unfused protein in Escherichia coli. The 28-kDa protein was shown to be catalytically active.

Cardiac glycoside-like structure and function of 5 beta,14 beta-pregnanes.

5 beta-Reduction and 14 beta-substitution convert the planar progesterone molecule to the cardiac glycoside configuration--A and D rings of the steroid moiety are bent toward the alpha-face relative to the B and C rings. Potency of the 5 beta,14 beta-derivative in a [3H]ouabain binding assay or its ability to inhibit the sodium pump in red blood cells is enhanced by 3 beta-hydroxylation, 20 beta-hydroxylation, and 3 beta-glycosidation. Synthesis of 14,20 beta-dihydroxy-3 beta-(beta-D-glucopyranosyloxy)- 5 beta,14 beta-pregnane from digitoxin is described. The glucoside is 1/20 as potent as ouabain and elicits prominent, sustained, positive inotropy in isolated cardiac muscle.

Progesterone derivatives that bind to the digitalis receptor: synthesis of 14 beta-hydroxyprogesterone. A novel steroid with positive inotropic activity.

The synthesis of 14-hydroxy-14 beta-pregn-4-ene-3,20-dione (14 beta-hydroxyprogesterone) is described. This novel steroid is about 10 times more potent than progesterone and one-tenth as potent as ouabagenin in an [3H]ouabain radioligand binding assay and is the first in a series of progesterone congeners that interact at the cardiac glycoside receptor both to possess the C/D cis ring junction and to enhance contractility of isolated cardiac tissue.

Pregnanes that bind to the digitalis receptor: synthesis of 14-hydroxy-5 beta,14 beta-pregnane glycosides from digitoxin and digitoxigenin.

The preparation of the mono-, bis-, and trisdigitoxosides of 14-hydroxy-5 beta,14 beta-pregnan-20-one and 14,20 beta-dihydroxy-5 beta,14 beta-pregnane by two routes, based on the conversion of the alpha,beta-unsaturated gamma-lactone in digitoxin to the 20-ketone and 20 beta-alcohol by ozonolysis and zinc-acetic acid treatment followed by lithium tri-tert-butoxyaluminum hydride reduction, are described. Synthesis of the alpha-L-rhamnoside derivatives is described also. Structures were confirmed by 1H and 13C NMR spectra. These derivatives show strong interaction with the cardiac glycoside receptor of heart muscle in an [3H]ouabain radioligand binding assay. Structure-activity relationships which are reported for glycosides and genins show that the alpha-L-rhamnoside derivatives are more potent than the beta-D-digitoxoside or the beta-D-glucoside and that the beta-D-glucosides are more potent than the mono-, bis-, and trisdigitoxosides. Potency is not increased by the addition of the second and third digitoxose units.

14 beta-Hydroxyprogesterone binds to the digitalis receptor, inhibits the sodium pump and enhances cardiac contractility.

1. Certain derivatives of progesterone are potent inhibitors of high affinity, specific binding of 3H-cardiac glycosides. The steroids interact at the cardiac glycoside site on Na,K-ATPase and inhibit the enzyme (the sodium pump) in cardiac and other tissues. However, the active congeners identified previously have been, unlike the cardiac glycosides, predominantly cardiodepressant. 2. Because a 14 beta-hydroxy substituent is an important determinant of activity of the cardiotonic cardiac glycosides, we synthesized 14 beta-hydroxyprogesterone. This derivative has about one-tenth the potency of the aglycone, ouabagenin, in a [3H]-ouabain binding assay. 3. Like ouabagenin, but in contrast to the cardiodepressant congeners of progesterone, 14 beta-hydroxyprogesterone consistently elicited positive inotropy in isolated cardiac muscle and enhanced both the magnitude and frequency of fluctuations in scattered light (an index of oscillatory intracellular release of calcium). 4. Thus, at least one hydroxylated derivative (and putative endogenous metabolite) of progesterone, mimics the cardiac effects of cardiac glycosides including enhanced contractility.

Synthesis and structure-activity relationships of 14 beta-hydroxy-5 alpha-pregnanes: pregnanes that bind to the cardiac glycoside receptor.

5 alpha-pregnane-3 beta,14 beta,20 beta-triol 3-alpha-L-rhamnopyranoside (8) and 3 beta-(alpha-L-rhamnopyranosyloxy)-5 alpha-pregn-14-en-20-one (14) were prepared from uzarigenin by ozonolysis followed by zinc and acetic acid reduction and glycosidation. During the glycosidation reaction leading to (8) the corresponding ortho ester (9) was also obtained. Uzarigenin alpha-L-rhamnopyranoside (15) also was prepared. Synthesis of 5 alpha-pregnane-3 beta,14 beta,20 beta-triol (20) is described. Structures were established by analysis of their NMR spectra. The binding affinity of 5 alpha and 5 beta cardenolide and pregnane derivatives as measured in a radioligand binding assay was determined and their structure-activity relationships compared. The receptor binding affinity of the 5 alpha derivatives is less than that of the corresponding 5 beta derivatives.

Structure-activity relationships of progesterone derivatives that bind to the digitalis receptor: modifications in A and B rings.

A number of progesterone derivatives, having a 17 alpha-acetoxy group and various functions at C-3 and C-6, interact at the cardiac glycoside (CG) binding site, using [3H]ouabain in a radioligand binding assay (RBA) with membranes from dog myocardium. We now report on results of structure-activity studies concerned with modification of the A and B rings as they influence potency in the RBA. Some progesterone derivatives with 5 alpha- or 5 beta-stereochemistry show weak receptor competing activity. Among the congeners highest potency is associated with the presence of C-4 or C-4,6 unsaturation and a C-6 substituent (CH3, Cl, Br) whose importance appears to reside in its steric rather than electronic character. The C-3 function may be carbonyl, 3 beta-hydroxy or 3 beta-acetoxy when associated with C-4 or C-4,6 unsaturation. In compounds with other substituents that promote activity, C-6 alpha substitution with -CH3, -Cl, or -Br strongly enhances activity; -F, -OCH3, carbonyl, or the unsubstituted compound promotes weak binding; and -OC2H5, -OAc, -OCOOCH3, or -OH eliminates binding activity. Receptor interaction with the double bond at C-4, but not C-5, appears to be particularly important for binding. The most potent analog identified thus far is chlormadinone acetate (17 alpha-acetoxy-6-chloropregna-4,6-diene-3,20-dione), which has 1/20 the potency of ouabain in the RBA. Studies to determine optimal structural requirements for CG-receptor binding by these hormonal steroid congeners, in conjunction with appropriate biological assays, may provide insight into the nature of a putative endogenous counterpart, lead to a better understanding of the mode of action of the CG and yield CG-like compounds with superior therapeutic properties.

Stereoselective reduction of C-2 substituted steroid C-3 ketones with lithium tris-(R,S-1,2-dimethylpropyl)-borohydride and sodium borohydride.

The effect of C-2 substitution on the stereoselective reduction of steroid C-3 ketones with lithium tris-(R,S-1,2-dimethylpropyl)-borohydride and sodium borohydride was investigated. The C-2 mono- and di-substituted chloro and methyl derivatives were predominantly reduced to one of the epimeric alcohols. The 2 alpha-chloro and 2 alpha-methyl derivatives of 17 beta-acetoxy-5 alpha-androstan-3-one undergo stereoselective reduction with lithium tris-(R,S-1,2-dimethylpropyl)-borohydride to the axial (3 alpha) alcohol as observed in the unsubstituted compound, whereas sodium borohydride gives predominantly the equatorial (3 beta) alcohol. The 2 beta-chloro, 2 beta-methyl, 2,2-dichloro, and 2,2-dimethyl derivatives are reduced predominantly to the equatorial (3 beta) alcohol by both reagents.

Stress fractures around the knee in elderly patients. A cause of acute pain in the knee.

A review of the cases of sixteen elderly patients who had eighteen stress fractures around the knee revealed that thirteen fractures had been misdiagnosed, which led to inappropriate management of six. The most frequent factor contributing to misdiagnosis was the presence of other abnormalities of the knee for which the patient had previously consulted the physician. Conservative treatment with rest, walking aids, and, for some patients, splinting of the extremity resulted in relief of pain and healing of the fracture. A careful clinical assessment that includes new radiographs and, if necessary, bone scans is essential for early diagnosis in patients who have acute, incapacitating pain in the knee.

High risk HPV types in southern Iranian patients with cervical cancer.

This study was undertaken to assess the rate of HPV infection in cervical carcinoma among southern Iranian patients. 101 archival cervical carcinoma tissue samples of a 10 year period were studied for the presence of HPV DNA in southern Iran by a polymerase chain reaction method. In addition, the presence of high risk HPV-16 and HPV-18 genotypes was investigated. In total, 88 (87.1%) of the samples were HPV DNA positive, of which 83 were squamous cell carcinomas and 5 were adenocarcinomas. HPV-16 genotype was detected in 26.7% of HPV positive cervical carcinomas; however, none of the samples were positive for the existence of HPV-18 genotype. Collectively, these results suggest that HPV-16 and HPV-18 are not the frequent high risk HPV types in our patients and circulating HPV types in southern Iranian population are different from many other populations.