Limited bedding and nesting increases ethanol drinking in female rats.

Prenatal opioid exposure (POE) and postnatal adverse experiences are early life adversities (ELA) that often co-occur and increase problematic alcohol (EtOH) drinking during adolescence. We investigated the relationship between POE, postnatal adversity, and adolescent EtOH drinking in rats. We also sought to determine whether ELAs affect alpha-adrenoceptor density in the brain because the noradrenergic system is involved in problematic alcohol drinking and its treatment. We hypothesized that the combination of POE and postnatal adversity will increase alcohol drinking in rats compared to rats with exposure to either adversity alone or to control. We also predicted that POE and postnatal adversity would increase α1-adrenoceptor density and decrease α2-adrenoceptor density in brain to confer a stress-responsive phenotype. Pregnant rats received morphine (15 mg/kg/day) or saline via subcutaneous minipumps from gestational day 9 until birth. Limited bedding and nesting (LBN) procedures were introduced from postnatal day (PD) 3-11 to mimic early life adversity-scarcity. Offspring rats (PD 31-33) were given opportunities to drink EtOH (20 %, v/v) using intermittent-access, two-bottle choice (with water) procedures. Rats given access to EtOH were assigned into sub-groups that were injected with either yohimbine (1 mg/kg, ip) or vehicle (2 % DMSO, ip) 30 min prior to each EtOH access session to determine the effects of α2-adrenoceptor inhibition on alcohol drinking. We harvested cortices, brainstems, and hypothalami from EtOH-naïve littermates on either PD 30 or PD 70 and conducted radioligand receptor binding assays to quantify α1- and α2-adrenoceptor densities. Contrary to our hypothesis, only LBN alone increased EtOH intake in female adolescent rats compared to female rats with POE. Neither POE nor LBN affected α1- or α2-adrenoceptor densities in the cortex, brainstem, or hypothalamus of early- or late-aged adolescent rats. These results suggest a complex interaction between ELA type and sex on alcohol drinking.

Decipher correlation patterns post prostatectomy: initial experience from 2 342 prospective patients.

BACKGROUND: Currently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we examined the correlation patterns of Decipher assay to understand the relationship between the Decipher and patient tumor characteristics. METHODS: De-identified Decipher test results (including Decipher risk scores and clinicopathologic data) from 2 342 consecutive radical prostatectomy (RP) patients tested between January and September 2015 were analyzed. For clinical testing, tumor specimen from the highest Gleason grade was sampled using a 1.5 mm tissue punch. Decipher scores were calculated based on a previously locked model. Correlations between Decipher score and clinicopathologic variables were computed using Spearman's rank correlation. Mixed-effect linear models were used to study the association of practice type and Decipher score. The significance level was 0.05 for all tests. RESULTS: Decipher score had a positive correlation with pathologic Gleason score (PGS; r=0.37, 95% confidence interval (CI) 0.34-0.41), pathologic T-stage (r=0.31, 95% CI 0.28-0.35), CAPRA-S (r=0.32, 95% CI 0.28-0.37) and patient age (r=0.09, 95% CI 0.05-0.13). Decipher reclassified 52%, 76% and 40% of patients in CAPRA-S low-, intermediate- and high-risk groups, respectively. We detected a 28% incidence of high-risk disease through the Decipher score in pT2 patients and 7% low risk in pT3b/pT4, PGS 8-10 patients. There was no significant difference in the Decipher score between patients from community centers and those from academic centers (P=0.82). CONCLUSIONS: Although Decipher correlated with baseline tumor characteristics for over 2 000 patients, there was significant reclassification of tumor aggressiveness as compared to clinical parameters alone. Utilization of the Decipher genomic classifier can have major implications in assessment of postoperative risk that may impact physician-patient decision making and ultimately patient management.

A knotless bidirectional-barbed tendon repair is inferior to conventional 4-strand repairs in cyclic loading.

UNLABELLED: We divided 21 flexor digitorum profundus tendons in the index, middle and ring fingers in seven cadaver hands into three groups. The tendons were cut in zone 2 and repaired using a 4-strand cruciate core suture repair with one of the following three materials in each group: (1) a knotless repair with a 2-0 bidirectional-barbed suture, which has similar tensile strength as a 4-0 non-barbed suture used in the other two groups; (2) a knotted locking repair with a non-barbed 4-0 conventional suture; and (3) a non-locking repair with a non-barbed 4-0 knotless suture. The repaired fingers were cyclically loaded through a simulated active range of motion to a 5 N load. We monitored and recorded the gap sizes at regular intervals during the test. The 2-0 bidirectional-barbed suture group and non-barbed suture groups developed gaps of 2.2 mm after 10 cycles and 2.4 mm after 20 cycles, respectively. Over 1000 cycles, the mean gaps were 3.2 mm in the 4-0 conventional suture group and 9.1 mm in the 2-0 bidirectional-barbed group. The tendons in the 2-0 bidirectional-barbed group gapped earlier, with statistically significant differences compared with those in the locking repair with a non-barbed 4-0 knotless suture group. The repair strength of the barbed suture technique was inferior to the cruciate repairs using a conventional 4-0 non-barbed suture tested in this cyclic-loading model. LEVEL OF EVIDENCE: Level V.

Significant differences among physician specialties in management recommendations of BRCA1 mutation carriers.

The National Comprehensive Cancer Network (NCCN) has published guidelines for hereditary breast and ovarian cancer syndrome (HBOCS) management. Little data exist on compliance with these guidelines among different physician specialties. We performed an on-line case-based survey by randomly sampling physicians from five specialties, Family Medicine (FM), Obstetrics and Gynecology (OG), General Surgery (GS), Internal Medicine (IM), and Hematology and Oncology (HO). The physicians (n = 225) were asked to provide HBOCS management of healthy women ages 40-42 in the presence of a familial BRCA1 mutation. For women negative for the BRCA1 mutation, 59% of the physicians recommended appropriate surveillance although with significant differences among specialties; P = 0.01. Using an aggregate screening intensity score, physicians clearly recommended more intense screening for mutation positive than negative women (P < 0.0001), but only 16% of physicians followed NCCN guidelines for BRCA1-positive women. Seventy-six percent of all physicians recommended breast MRI with significant variation among specialties ranging from 62% of FM to 89% of OG (P = 0.0020). Similarly, 63% of physicians recommended prophylactic oophorectomy, with 76 and 78% of GS and OG compared to 38% of IM (P < 0.0001) and 57% recommended prophylactic mastectomy ranging from 84% of HO to 32% of FM (P < 0.0001). Independent of specialty, respondents with BRCA testing experience recommended more intense management than those without; P = 0.021. Management recommendations of BRCA1 mutation carriers are not consistent with NCCN guidelines and vary by medical specialty and genetic testing experience. Targeted education of physicians by specialty is needed, so that optimal management is offered to these high-risk women.

Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial.

OBJECTIVE: B cells and the humoral immune system have been implicated in the pathogenesis of multiple sclerosis (MS). This study sought to evaluate the efficacy, safety, and tolerability of add-on therapy with rituximab, a monoclonal antibody that depletes circulating B cells, in subjects with relapsing MS with breakthrough disease defined by clinical and MRI activity (Class III evidence). METHODS: Thirty subjects with a relapse within the past 18 months despite use of an injectable disease-modifying agent, and with at least 1 gadolinium-enhancing (GdE) lesion on any of 3 pretreatment MRIs, received rituximab administered at 375 mg/m(2) weekly x 4 doses. Three monthly posttreatment brain MRI scans were obtained beginning 12 weeks after the first infusion. Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were obtained at baseline and throughout the posttreatment follow-up. RESULTS: GdE lesions were reduced after treatment with rituximab, with 74% of posttreatment MRI scans being free of GdE activity compared with 26% free of GdE activity at baseline (p < 0.0001). Median GdE lesions were reduced from 1.0 to 0, and mean number was reduced from 2.81 per month to 0.33 after treatment (88% reduction). MSFC improved as well (p = 0.02). EDSS remained stable. CONCLUSION: Rituximab add-on therapy was effective based upon blinded radiologic endpoints in this phase II study. In combination with standard injectable therapies, rituximab was well-tolerated with no serious adverse events. B-cell-modulating therapy remains a potential option for treatment of patients with relapsing MS with an inadequate response to standard injectable therapies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that add-on rituximab reduces gadolinium-enhancing brain lesions in multiple sclerosis.

Clinical and laboratory assessment of distal peripheral nerves in Gulf War veterans and spouses.

BACKGROUND: The prevalence of symptoms suggesting distal symmetric polyneuropathy (DSP) was reported to be higher among deployed veterans (DV) to the Persian Gulf in 1990-1991 than to control non-deployed veterans (NDV). The authors therefore compared the prevalence of DSP by direct examination of DV and their spouses to control NDV and spouses. METHODS: The authors performed standardized neurologic examinations on 1,061 DV and 1,128 NDV selected from a cohort of veterans who previously participated in a national mail and telephone survey. Presence of DSP was evaluated by history, physical examination, and standardized electrophysiologic assessment of motor and sensory nerves. Similar examinations were performed without electrophysiologic tests in 484 DV spouses and 533 NDV spouses. Statistical analyses were performed with appropriate adjustments for the stratified sampling scheme. RESULTS: No differences between adjusted population prevalence of DSP in DV and NDV were found by electrophysiology (3.7% vs 6.3%, p = 0.07), by neurologic examination (3.1% vs 2.6%, p = 0.60), or by the methods combined (6.3% vs 7.3%, p = 0.47). Excluding veterans with non-military service related diseases that may cause DSP did not alter outcomes. DV potentially exposed to neurotoxins from the Khamisiyah ammunition depot explosion did not significantly differ in DSP prevalence compared to non-exposed DV. The prevalence of DSP in DV spouses did not differ from NDV spouses (2.7% vs 3.2%, p = 0.64). CONCLUSIONS: Neither veterans deployed during the Gulf War era nor their spouses had a higher prevalence of DSP compared to NDV and spouses.

"Fou rire prodromique" as the presentation of pontine ischaemia secondary to vertebrobasilar stenosis.

"Fou rire prodromique" (prodrome of crazy laughter) is a rare form of pathological laughter of uncertain pathophysiology. A patient is presented with pathological laughter as the first manifestation of pontine ischaemia due to vertebrobasilar stenosis. A 65 year old man developed uncontrollable and unemotional laughter for almost an hour followed by transient right facial-brachial paresis. He had fluctuation of laughter, right facial brachial paresis, and occasional crying. Magnetic resonance imaging, magnetic resonance angiogram (MRA), and an angiogram showed small left pontine and cerebellar infarcts, left vertebral artery occlusion, and right vertebral and basilar artery stenosis. His condition deteriorated to bilateral brain stem infarction and he died. Necropsy confirmed the extensive brain stem infarction. Pathological laughter can be the very first presenting manifestation of ischaemia of the ventrotegmental junction of the upper pons. It is hypothesised that the pathological laughter in this patient was secondary to ischaemic ephaptic stimulation of the descending corticopontine/ bulbar pathways.

Tibiotalocalcaneal arthrodesis: a biomechanical analysis of the rotational stability of the Biomet Ankle Arthrodesis Nail.

We hypothesized that the posterior-to-anterior (PA) calcaneal interlocking screw of the Biomet Ankle Arthrodesis Nail would increase rotational stability secondary to increased bone purchase compared with the standard lateral-to-medial (transverse) screw. Each of 10 fresh human cadaver lower limbs (five matched pairs) were stabilized with a nail inserted retrograde through the calcaneus, talus, and tibia according to standard technique. One limb of each pair was fixed with a transverse calcaneal screw; the contralateral limb, with a PA calcaneal screw. Each limb was then subjected to torsional testing on an MTS Mini Bionix load frame. The PA screw construct was significantly stiffer than the transverse screw construct: 1.96 and 1.41 Nm/E, respectively (P < 0.036).

Photocontrol of stem growth.

Rapid and measurable growth rate changes that occur in seedling stems upon illumination serve as an excellent means to analyze signal transduction. Growth kinetic studies have shown how red, far-red and blue light signals are transduced via the solitary and/or coordinated action of known plant photoreceptors. These reports are consistent with current findings describing light-induced photoreceptor interaction and compartmentation.

Light-induced growth promotion by SPA1 counteracts phytochrome-mediated growth inhibition during de-etiolation.

Previous evidence has suggested that SPA1 is a signal transduction component that appears to require phytochrome A for function in seedling photomorphogenesis. Using digital image analysis, we examined the time course of growth inhibition induced by red light in spa1 mutants to test the interpretation that SPA1 functions early in a phyA-specific signaling pathway. By comparing wild-type and mutant responses, we found that SPA1 caused an increase in hypocotyl growth rate after approximately 2 h of continuous red light, whereas the onset of phyA-mediated inhibition was detected within several minutes. Thus, SPA1-dependent growth promotion began after phyA started to inhibit growth. The action of SPA1 persisted for approximately 2 d of red light, a period well beyond the time when the phyA photoreceptor and its influence on growth have both decayed to undetectable levels. Also, SPA1 promoted growth for many hours in the complete absence of a light stimulus when red-light-grown seedlings were shifted to darkness. We propose that SPA1 functions in a light-induced mechanism that promotes growth and thereby counteracts growth inhibition mediated by phyA and phyB. Our finding that spa1 seedlings do not display growth promotion in response to end-of-day pulses of far-red light, even in a phyA-null background, supports this interpretation. Combined, these results lead us to the view that the rate of hypocotyl elongation in light is determined by at least two independent, opposing processes; an inhibition of growth by the phytochromes and a promotion of growth by light-activated SPA1.

The contribution of the medial calcaneal osteotomy to the correction of flatfoot deformities.

HYPOTHESES/PURPOSE: The success of the medial displacement calcaneal osteotomy in correcting flatfoot deformities is likely to be the result of a shift of the Achilles tendon forces on the hindfoot. The purpose of this study was twofold: 1) to define the contribution of the Achilles tendon to the flatfoot deformity, and 2) to define the effect of a calcaneal medial displacement osteotomy. METHODS: We used six different experimental dynamic stages: 1) intact foot without Achilles loading; 2) intact foot with Achilles loading; 3) flatfoot without medial calcaneal displacement osteotomy and without Achilles loading; 4) flatfoot without medial calcaneal displacement osteotomy but with Achilles loading; 5) flatfoot with medial calcaneal displacement osteotomy but without Achilles loading; and 6) flatfoot with medial calcaneal displacement osteotomy and with Achilles loading. The experimental flaffoot was developed by releasing the posterior tibial tendon, spring ligament, and plantar fascia and applying 7,000 cycles of axial fatigue load (range, 700 to 1,400 N; 1-Hz frequency). To simulate the phase of midstance, the peroneus longus, peroneus brevis, flexor digitorum longus, and flexor hallucis longus tendons were grasped by clamps, connected to pneumatic actuators, and loaded with precalculated forces. Anteroposterior and lateral radiographs were obtained for each stage on which the following measurements were made: talonavicular coverage angle, talar-first metatarsal angle, talocalcaneal angle, and height of the medial cuneiform. These measurements were compared with a one-way ANOVA. RESULTS: Between stages 1 and 2, all measurements were statistically insignificant. Between stages 3 and 4, for all measurements, Achilles tendon loading aggravated the flatfoot deformity (p < 0.05). After medial calcaneal osteotomy (stages 5 and 6), the Achilles tendon contributed less to the arch-flattening. We found that the medial displacement osteotomy plays an important role in reducing and/or delaying the progress of flatfoot deformity. CONCLUSIONS/SIGNIFICANCE: In the flatfoot, loading of the Achilles tendon increases the deformity. Medial calcaneal osteotomy significantly decreases the arch-flattening effect of this tendon and therefore limits the potential increase of the deformity.

Biomechanical evaluation of the ability of casts and braces to immobilize the ankle and hindfoot.

We evaluated the ability of seven devices to immobilize a prosthetic ankle-foot complex against plantarflexion, dorsiflexion, inversion, and eversion forces: two casts (plaster of Paris and Fiberglas) and five removable braces (molded ankle/foot orthosis, composite boot brace, pneumatic boot walker, nonarticulating fracture boot, and ankle stirrup). Each device was applied to a prosthetic ankle-foot complex and evaluated on a test frame for resistance to sagittal motion and coronal torque. Results showed that casts offered significantly (P < or = 0.05) more resistance to motion in all directions tested than did the braces. The resistance offered by the devices tested depends on the conformity of the device to the shape of the foot in that plane and the material properties of the device. Braces offer the advantage of being easily removed and reapplied. Different braces offer specific advantages and disadvantages in different planes tested, and immobilization selection should be individualized based on this information.

Experimental flatfoot model: the contribution of dynamic loading.

The goal of this study was to determine if the application of muscle forces (simulating the dynamic phase of the midstance part of gait) had an effect on flatfoot deformity. We created a flatfoot model in each of seven cadaver foot specimens by grasping the Achilles, peroneus longus, peroneus brevis, flexor digitorum longus, and flexor hallucis longus tendons with soft-tissue vice clamps connected via wire cables to pneumatic cylinders. The experiment included four stages: 1) initial static axial loading; 2) axial loading after 3,000 load cycles (average, 735 N; range, 70 to 1400 N); 3) axial loading after releasing the spring ligament and plantar fascia; and 4) axial loading after an additional 3,000 load cycles. At each stage, both static (with axial loading only) and dynamic (axial loading with tensioning of the tendons to simulate the muscle forces at midstance) conditions were evaluated radiographically. No change was observed between the static and dynamic conditions in the first two phases of the experiment. After the third phase, changes in the talar-first metatarsal angle and the height of the medial cuneiform were noted, particularly in the dynamic condition. These and additional radiographic changes were magnified in the fourth phase, but only in the dynamic condition. We concluded that, to create an effective flatfoot model, the medial structures, including the spring ligament and possibly the plantar fascia, must be severed. Cyclic loading of the foot further increased the arch flattening, and this effect was magnified by dynamic loading.

Analysis of metal incorporation during overexpression of Clostridium pasteurianum rubredoxin by electrospray FTICR mass spectrometry.

The rate of production of Clostridium pasteurianum rubredoxin overexpressed in Escherichia coli was examined by electrospray ionization-Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry. Previous work had shown that this heterologous expression resulted in isolation of both iron-containing (FeRd) and zinc-containing (ZnRd) rubredoxins. In the present work, minimally processed cell lysates of E. coli were analyzed in order to monitor the production of FeRd and ZnRd. The sensitivity of the measurement favored FeRd relative to ZnRd, and this differential sensitivity was quantitated using previously separated and purified rubredoxins. A time course study indicated that ZnRd and FeRd are produced simultaneously during overexpression, but at different rates. The ratio of the concentration of ZnRd to FeRd increased in a linear fashion during 3 h following induction of overexpression. Since only FeRds have been reported from native bacteria and archaea, the data suggest that either Zn2+ is sequestered from rubredoxins during native biosynthesis or that ZnRds may have escaped detection in the native microorganisms. ESI-FTICR mass spectrometry is shown to be a useful tool for monitoring metal insertion during protein biosynthesis.

Cyclic loading of rotator cuff repairs: A comparison of bioabsorbable tacks with metal suture anchors and transosseous sutures.

PURPOSE: The purposes of the study were (1) to compare rotator cuff repair strengths after cyclic loading of 2 bioabsorbable nonsuture-based tack-type anchors, transosseous sutures, and a metal suture-based anchor, and (2) to correlate bone mineral density with mode of failure and cycles to failure. We hypothesized that specimens with a lower bone density would fail through bone at a lower number of cycles independent of the method of cuff fixation. TYPE OF STUDY: Ex vivo biomechanical study. METHODS: Standardized full-thickness rotator cuff defects were created in 30 fresh-frozen cadaveric shoulders that were randomized to 1 of 4 repair groups: transosseous sutures; Mitek Super suture anchors (Mitek Surgical Products, Westwood, MA); smooth bioabsorbable 8-mm Suretacs (Acufex, Smith & Nephew Endoscopy, Mansfield, MA); or spiked bioabsorbable 8-mm Suretacs (Acufex). All repairs were cyclically loaded from 10 to 180 N; the numbers of cycles to 50% (gap, 5 mm) and 100% (gap, 10 mm) failure were recorded. RESULTS: In comparing the repair groups, we found only 1 significant difference: the number of cycles to 100% failure was significantly higher (P <.05) for the smooth bioabsorbable tack than for the transosseous suture group. There were no statistically significant (P

Pediatric patients with undetectable anticonvulsant blood levels: comparison with compliant patients.

Undetectable anticonvulsant blood levels indicate sustained noncompliance (several consecutive doses missed). We compared 91 consecutive outpatients with epilepsy and undetectable anticonvulsant blood levels to 100 patients seen during the same time period, verified as compliant by acceptable serum levels. We hypothesized that pay status, application for Supplemental Security Income, patient age, history of missed appointments, and functional status would differ between compliant and noncompliant patients. We were surprised to find large differences between clinic and insurance patients and between Caucasian and non-Caucasian patients. The 100 compliant patients included 44 Caucasian and 56 non-Caucasian patients, whereas only 9 of 91 noncompliant patients were Caucasian, and only 9 had insurance, compared to 32 compliant patients. Applications for Supplemental Security Income and history of missed appointments were significantly associated with noncompliance, but patient age, seizure type, and seizure control were not. Uninsured Caucasians were more often compliant than non-Caucasians were. Many noncompliant patients had mild epilepsy, which was reportedly doing well. Race and pay status were closely correlated. Several noncompliant females became pregnant, whereas no compliant patients did. Compliant patients were much more likely to be accompanied by a parent or caretaker on clinic visits than noncompliant patients. Noncompliant patients had at least one acceptable subsequent serum level, although 2 patients with intractable epilepsy had undetectable serum levels on three or more occasions. Noncompliance may respond to discussion and advice. We reviewed 124 episodes of undetectable drug levels in the 91 noncompliant patients. Eighteen of these resulted in hospitalization, but in 25 cases, we were told that there had been no seizures since the preceding visit. Many noncompliant patients have infrequent seizures, even if they take little or no medication. Socioeconomic status influences health, life expectancy, and educational success, but it has been claimed to be irrelevant to compliance and adherence issues in epilepsy. Our data and the experience of other centers with childhood diabetes suggest that socioeconomic, racial, and family factors influence compliance or adherence to treatment for many chronic conditions. Educational efforts and support for parents at the start of anticonvulsant treatment may improve compliance. Uninsured patients missed more appointments and were much more likely to be noncompliant than insured patients. Attention to the special problems of Medicaid and minority children is needed.

Dorsiflexion contracture after the Weil osteotomy: results of cadaver study and three-dimensional analysis.

For metatarsalgia caused by a dislocated lesser metatarsophalangeal (MTP) joint and isolated over-long lesser metatarsals, surgical treatment options without sacrificing the joint are limited. Recently, the Weil osteotomy has been advocated for the treatment of this deformity. In our experience, preliminary results with this technique have revealed a high rate of dorsiflexion contracture of the MTP joints at follow-up. We performed a cadaver study and a three-dimensional analysis on sawbones to investigate this phenomenon. In the cadaveric portion of this study, the second MTP joints of two fresh-frozen cadavers were dissected; the entire ray, with the metatarsal shaft, MTP joint, toe, and plantar fascia, was removed en bloc. After gross anatomic structures were photographed, a Weil osteotomy was performed at 25 degrees relative to the long axis of the metatarsal shaft. The positions of muscles, ligaments, and tendons were noted and photographed before and after the osteotomy. In the sawbones portion of this study, a Weil osteotomy was performed at four different angles (25 degrees, 30 degrees, 35 degrees, and 40 degrees) relative to the long axis of the metatarsal. To ensure reproducibility, the sawbone models were fixed proximally to a vertical milling machine with the second metatarsals inclined 15 degrees to simulate the anatomic position. After making the cut, the plantar fragment was translated along the dorsal fragment proximally for a distance of 5 mm. Before and after the osteotomy, selected x, y, and z coordinates were obtained using a Microscribe 3D digitizer. Data analysis was performed with Microsoft Excel, and ANOVA was used to determine significant differences (p < 0.05) between the various osteotomies. Analysis of the cadaver dissection revealed that after the Weil osteotomy, the tendons of the interosseous muscles move dorsally with respect to the axis of the MTP joint due to the depression of the plantar fragment of the metatarsal. The loss of their flexion effect on the joint permits the pull of the extensor to dorsiflex the toe. The size of the depression for the various osteotomies averaged: 25 degrees osteotomy, 3.03 mm (range, 1.8 to 3.8 mm); 30 degrees osteotomy, 3.2 mm (range, 1.9 to 4.0 mm); 35 degrees osteotomy, 3.5 mm (range, 1.7 to 5.7 mm); and 40 degrees osteotomy, 4.2 mm (range, 2.8 to 6.4 mm). Amounts of shortening relative to the long axis of the metatarsal for the various osteotomies averaged: 25 degrees osteotomy, 5.03 mm (range, 4.77 to 5.30 mm); 30 degrees osteotomy, 4.59 mm (range, 3.47 to 5.19 mm); 35 degrees osteotomy, 4.27 mm (range, 2.87 to 5.00 mm); and 40 degrees osteotomy, 3.65 mm (range, 3.20 to 4.31 mm). According to our analysis, depression of the plantar fragment always occurs after a Weil osteotomy. This depression changes the center of rotation of the MTP joint, and the interosseous muscles then act more as dorsiflexors than as plantarfexors.

Six first metatarsal shaft osteotomies: mechanical and immobilization comparisons.

Because malunion (usually with dorsal elevation of the first metatarsal) has been reported after the treatment of severe hallux valgus deformities by proximal osteotomies, the current study was designed to compare the sagittal stability of six different metatarsal shaft osteotomies: the proximal crescentic, proximal chevron, Mau, Scarf, Ludloff, and biplanar closing wedge osteotomies. A plate was used in the biplanar closing wedge osteotomy; all others used screws for fixation. Ten fresh-frozen, human anatomic lower extremity specimens were used for each osteotomy. Failure loads were measured as units of force (newtons) and converted to pressure (kilopascals). Then the F-Scan system, which uses a thin insole to measure plantar pressure, was used to evaluate the pressure under the first metatarsal of seven volunteers using four types of shoes. According to the results, in patients with normal bone stock who are compliant, any of the four shoe types tested may be used after a Ludloff, Scarf, biplanar wedge (plantar screw fixation), or Mau osteotomy, but the wedge-based shoe should be used after a proximal crescentic or chevron osteotomy or for patients with severe osteopenic bone.

Anticonvulsant blood levels: historical review with a pediatric focus.

Epilepsy is heterogeneous and its treatment is often complicated by variable drug responses. Buchtal et al reported a close correlation between serum phenytoin levels, electroencephalographic findings, and clinical status in 1960. They suggested that physicians adjust dosage to attain a "therapeutic level." The concept was enthusiastically received. "Therapeutic serum levels" were proposed for most anticonvulsant drugs, and by 1975, most authorities believed that pharmacokinetic factors explained individual differences in drug response. However, Froscher found that measuring levels did not improve patient outcome. More recently, Schumacher's double-blind study found no correlation between phenytoin levels and seizure control or adverse effects. Pharmacodynamic variables (differences in drug responsiveness) are more important than pharmacokinetic factors for many drugs, especially receptor-active drugs. Pharmacokinetic variables were studied first, and led to a simplistic model. They are less significant than pharmacodynamic factors in the case of warfarin anticoagulation. Anticonvulsant levels can reveal noncompliance and pharmacokinetic differences. They say nothing about pharmacodynamics. Reports of "subtherapeutic levels" imply a need to increase dosage, but this is not supported by outcome data. We still lack evidence that specific drug levels are a valid intermediate target 40 years after Buchtal's paper. Responses to some anticonvulsants could depend primarily on pharmacokinetic factors, while pharmacodynamic factors could be supreme for others.