Outcomes of ulna shortening osteotomy: a cohort analysis of 106 patients.

BACKGROUND: Ulna shortening osteotomy (USO) for ulnar impaction syndrome (UIS) aims to improve pain and function by unloading the ulnar carpus. Previous studies often lack validated patient-reported outcomes or have small sample sizes. The primary objective of this study was to investigate patient-reported pain and hand function at 12 months after USO for UIS. Secondary objectives were to investigate the active range of motion, grip strength, complications, and whether outcomes differed based on etiology. MATERIALS AND METHODS: We report on 106 patients with UIS who received USO between 2012 and 2019. In 44 of these patients, USO was performed secondary to distal radius fracture. Pain and function were measured with the Patient Rated Wrist/Hand Evaluation (PRWHE) before surgery and at 3 and 12 months after surgery. Active range of motion and grip strength were measured before surgery and at 3 and 12 months after surgery. Complications were scored using the International Consortium for Health Outcome Measurement Complications in Hand and Wrist conditions (ICHAW) tool. RESULTS: The PRWHE total score improved from a mean of 64 (SD = 18) before surgery to 40 (22) at 3 months and 32 (23) at 12 months after surgery (P < 0.001; effect size Cohen's d = -1.4). There was no difference in the improvement in PRWHE total score (P = 0.99) based on etiology. Also, no clinically relevant changes in the active range of motion were measured. Independent of etiology, mean grip strength improved from 24 (11) before surgery to 30 (12) at 12 months (P = 0.001). Sixty-four percent of patients experienced at least one complication, ranging from minor to severe. Of the 80 complications in total, 50 patients (47%) had complaints of hardware irritation, of which 34 (32%) had their hardware removed. Six patients (6%) needed refixation because of nonunion. CONCLUSION: We found beneficial outcomes in patients with UIS that underwent USO, although there was a large variance in the outcome and a relatively high number of complications (which includes plate removals). Results of this study may be used in preoperative counseling and shared decision-making when considering USO. LEVEL OF EVIDENCE: Therapeutic III.

Trapeziometacarpal arthrodesis or trapeziectomy with ligament reconstruction in primary trapeziometacarpal osteoarthritis: a randomized controlled trial.

BACKGROUND: Both trapeziectomy with ligament reconstruction and tendon interposition and trapeziometacarpal arthrodesis are commonly performed procedures for the treatment of trapeziometacarpal osteoarthritis. The purpose of this study was to compare the outcomes of both treatments for symptomatic osteoarthritis of the thumb trapeziometacarpal joint in a randomized trial. METHODS: Women who were forty years of age or older were randomized either to trapeziectomy with ligament reconstruction and tendon interposition or to arthrodesis with plate and screws. Patients were evaluated preoperatively and at three and twelve months postoperatively with respect to pain, function (Patient-Rated Wrist/Hand Evaluation [PRWHE] and Disabilities of the Arm, Shoulder and Hand [DASH] questionnaires), joint motion, strength, complication rate, and patient satisfaction. RESULTS: Forty-three patients were enrolled. Since we found significantly more moderate and severe complications following arthrodesis compared with trapeziectomy with ligament reconstruction and tendon interposition (71% versus 29%; p = 0.016), the study was prematurely terminated before the sample size necessary to validly compare the two groups was reached. The higher complication rate for arthrodesis led to an increase in revision surgery (two of seventeen patients). Significantly more patients in the ligament reconstruction and tendon interposition group (86%) than in the arthrodesis group (53%) indicated they would consider the same surgery again under the same circumstances (p = 0.025). In both groups, PRWHE and DASH scores significantly improved over time; however, comparison of the groups showed that the results were similar. CONCLUSIONS: Women who are forty years or older with trapeziometacarpal osteoarthritis have fewer moderate and severe complications after trapeziectomy with ligament reconstruction and tendon interposition and are more likely to consider the surgery again under the same circumstances than are those who undergo arthrodesis. Twelve months after surgery, the PRWHE and DASH scores were similar in both groups. We do not recommend routine use of arthrodesis with plate and screws in the treatment of women who are forty years or older with stage-II or III trapeziometacarpal osteoarthritis.

Lapatinib: clinical benefit in patients with HER 2-positive advanced breast cancer.

BACKGROUND: Lapatinib, a tyrosine kinase inhibitor of human epidermal growth factor receptor 2 (HER2), has shown activity in combination with capecitabine in patients with HER2-positive advanced breast cancer progressive on standard treatment regimens. We present results on preapproval drug access for this combination in such patients occurring in the general oncology practice in the Netherlands. METHODS: Patients with HER2-positive advanced breast cancer progressive on schedules containing anthracyclines, taxanes, and trastuzumab were eligible. Brain metastases were allowed if stable. Lapatinib 1250 mg÷day was given continuously in combination with capecitabine 1000 mg÷m2 twice daily for two weeks in a three-week cycle. Efficacy was assessed by use of response evaluation criteria in solid tumours version 1.0. Progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Eighty-three patients were enrolled from January 2007 until July 2008. The combination was generally well tolerated and the most common drug-related serious adverse events were nausea and÷or vomiting (5%) and diarrhoea (2%). Seventy-eight patients were evaluable for response. Clinical benefit (response or stable disease for at least 12 weeks) was observed in 50 patients (64%) of whom 15 had a partial response and 35 stable disease. The median PFS and OS were 17 weeks (95% CI: 13 to 21) and 39 weeks (95% CI: 24 to 54), respectively. For OS, higher Eastern Cooperative Oncology Group (ECOG) status (p=0.016), brain metastases at study entry (p=0.010) and higher number of metastatic sites (p=0.012) were significantly negative predictive factors. CONCLUSION: In a patient population with heavily pretreated HER2-positive advanced breast cancer lapatinib plus capecitabine was well tolerated and offered clinical benefit.

Rise in maternal mortality in the Netherlands.

OBJECTIVE: To assess causes, trends and substandard care factors in maternal mortality in the Netherlands. Design Confidential enquiry into the causes of maternal mortality. SETTING: Nationwide in the Netherlands. POPULATION: 2,557,208 live births. METHODS: Data analysis of all maternal deaths in the period 1993-2005. MAIN OUTCOME MEASURES: Maternal mortality. RESULTS: The overall maternal mortality ratio was 12.1 per 100 000 live births, which was a statistically significant rise compared with the maternal mortality ratio of 9.7 in the period 1983-1992 (OR 1.2, 95% CI 1.0-1.5). The most frequent direct causes were (pre-)eclampsia, thromboembolism, sudden death in pregnancy, sepsis, obstetric haemorrhage and amniotic fluid embolism. The number of indirect deaths also increased, mainly caused by an increase in cardiovascular disorders (OR 2.5, 95% CI 1.4-4.6). Women younger than 20 years and older than 45 years, those with high parity or from nonwestern immigrant populations were at higher risk. Most substandard care was found in women with pre-eclampsia (91%) and in immigrant populations (62%). CONCLUSIONS: Maternal mortality in the Netherlands has increased since 1983-1992. Pre-eclampsia remains the number one cause. Groups at higher risk for complications during pregnancy should be better identified early in pregnancy or before conception, in order to receive preconception advice and more frequent antenatal visits. There is an urgent need for the better education of women and professionals concerning the danger signs, and for the training of professionals in order to improve maternal health care.

Ligament reconstruction arthroplasty for primary thumb carpometacarpal osteoarthritis (weilby technique): prospective cohort study.

PURPOSE: The Weilby procedure is one of several accepted methods to treat primary thumb carpometacarpal osteoarthritis. We found no previous studies that included preoperative and postoperative subjective outcomes using validated questionnaires or preoperative and postoperative objective outcomes such as specific strength and range-of-motion measurements. Therefore, we performed a prospective cohort study in which we analyzed preoperative and postoperative objective and subjective outcomes after Weilby interposition tendoplasty. METHODS: Nineteen patients (20 thumbs) with primary thumb carpometacarpal osteoarthritis were treated with Weilby interposition tendoplasty. For subjective assessment, the Disabilities of the Arm, Shoulder, and Hand (DASH) outcome data collection instrument was used to evaluate preoperative and postoperative outcomes at 0, 3, 6, and 12 months. Furthermore, patients completed a specific personal questionnaire at 12 months of follow-up. Objective assessments included interphalangeal joint flexion/extension; metacarpophalangeal joint flexion/extension; and carpometacarpal joint palmar abduction, opposition, and extension. Tip pinch, key pinch, 3-point pinch, and overall grip strengths were also measured. The measurements were performed preoperatively and at 3, 6, and 12 months after surgery. All complications were registered. RESULTS: The DASH score was significantly improved, and 17 of 19 patients were satisfied with the procedure. The interphalangeal joint flexion/extension, metacarpophalangeal joint flexion/extension, and carpometacarpal joint extension did not significantly change. Carpometacarpal joint palmar abduction and opposition were significantly improved at 12 months. The tip pinch and key pinch strengths were increased but not significantly. The 3-point pinch and overall grip strengths were significantly improved at 12 months. CONCLUSIONS: The Weilby procedure is a reliable alternative to treat primary thumb carpometacarpal osteoarthritis without requiring bone tunnel creation. It achieves pain relief, stability, mobility, and strength. The objective and subjective outcomes of this study compare favorably with those of earlier reports of the Weilby procedure and are similar to the published results of the more commonly performed Burton-Pellegrini technique. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Carpal boss: effect of wedge excision depth on third carpometacarpal joint stability.

PURPOSE: We hypothesize that carpal-metacarpal (CMC) instability after carpal boss wedge excision is not caused only by damage to the dorsal ligament but mainly depends on the depth of the bony resection. METHODS: To test our hypothesis, this study analyzes the effect of wedge excisions with different depths (0, 15%, 35%, 55% of the third CMC joint) and the effect of different forces (0, 50, 100 N.m) on the stability (measured as the passive flexion) of the third CMC joint using 12 fresh-frozen human cadaver wrists. The passive flexion is defined as the increase in angular motion of the third CMC joint and represents change in stability during flexion of the joint. RESULTS: The results show that the mean passive flexion measured in the wedge excisions of 15% and 35% of the joint did not differ from that of neutral controls. Joints analyzed after a 55% wedge excision showed a significant increase in angular motion (increased passive flexion). This relates to the 50 N.m as well as the 100 N.m loaded test position. CONCLUSIONS: This study shows that a wedge excision of clinically applicable depth of 35% does not create instability during flexion of the third CMC joint when loaded with physiologically relevant forces. Yet an extended and hardly clinically relevant 55% wedge excision results in a change in stability of the joint. To prevent instability when performing a wedge excision for symptomatic carpal boss, care must be taken to avoid excisions that exceed 35% of the third CMC joint.

Nanomechanical measurement of magnetostriction and magnetic anisotropy in (Ga,Mn)As.

A GaMnAs nanoelectromechanical resonator is used to obtain the first measurement of magnetostriction in a dilute magnetic semiconductor. Resonance frequency shifts induced by field-dependent magnetoelastic stress are used to simultaneously map the magnetostriction and magnetic anisotropy constants over a wide range of temperatures. Owing to the central role of carriers in controlling ferromagnetic interactions in this material, the results appear to provide insight into a unique form of magnetoelastic behavior mediated by holes.

Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter.

Leukoencephalopathy with vanishing white matter (VWM) is an inherited brain disease that occurs mainly in children. The course is chronic-progressive with additional episodes of rapid deterioration following febrile infection or minor head trauma. We have identified mutations in EIF2B5 and EIF2B2, encoding the epsilon- and beta-subunits of the translation initiation factor eIF2B and located on chromosomes 3q27 and 14q24, respectively, as causing VWM. We found 16 different mutations in EIF2B5 in 29 patients from 23 families. We also found two distantly related individuals who were homozygous with respect to a missense mutation in EIF2B2, affecting a conserved amino acid. Three other patients also had mutations in EIF2B2. As eIF2B has an essential role in the regulation of translation under different conditions, including stress, this may explain the rapid deterioration of people with VWM under stress. Mutant translation initiation factors have not previously been implicated in disease.

Changes in the vaginal flora after two percent clindamycin vaginal cream in women at high risk of spontaneous preterm birth.

OBJECTIVE: To analyse alterationS in the vaginal flora after 2% clindamycin vaginal cream or placebo administered for the prevention of preterm delivery in high risk women. DESIGN: Observational study during a randomised multicentre double-blind placebo controlled trial. SETTING: Twelve city hospitals in The Netherlands. PARTICIPANTS: One hundred and sixty-eight women were enrolled. Alterations in the vaginal flora could be analysed in one hundred and twenty-four women by comparing the Nugent score on entry to the trial and at 31 weeks' gestation. The Nugent score was classified into normal, intermediate and bacterial vaginosis. INTERVENTIONS: Two percent clindamycin vaginal cream or placebo cream administered daily for seven days at week 26 of pregnancy. MAIN OUTCOME: Changes in the vaginal flora at week 31 of pregnancy. RESULTS: The placebo group consisted of 64 women and the clindamycin group of 60 women. At week 31 the vaginal flora was similar to week 26 with placebo cream but changed from normal vaginal flora to intermediate or bacterial vaginosis with 2% clindamycin vaginal cream. CONCLUSION: Obstetricians should not prescribe 2% clindamycin vaginal cream to pregnant women with normal vaginal flora in order to reduce the incidence of preterm birth. because it has no beneficial effects and is actually harmful. 2% Clindamycin vaginal cream encourages the presence of bacterial vaginosis which is epidemiologically associated with preterm birth.

Rat lung MRI using low-temperature prepolarized helium-3.

The purpose of this study was to evaluate the recently proposed technique of 3He prepolarization at low temperature and high field (Kober et al. Magn Reson Med 1999; 41:1084-1087) for fast imaging of the lung. Helium-3 was cooled to 2.4 K in a magnetic field of 8 Tesla to obtain a polarization of 0.26%. The polarized 3He was warmed up to room temperature and transferred to a rat, with a final polarization of about 0.1%, large enough for acquiring a 3D image of the rat lung in 30 s.

Zero temperature spin wave damping in spin polarized 3He: does it exist?

Previous spin echo experiments at equilibrium polarizations in 3He- 4He mixtures have confirmed the prediction of zero temperature polarization-induced spin wave damping in Fermi liquids. We have measured the damping of spin waves in dilute 3He, spin polarized by a 4He circulating dilution refrigerator. The maximum polarization is almost a factor of 5 higher than the equilibrium polarization in a magnetic field of 10.54 T at temperatures between 10 and 25 mK. The spin wave damping is much smaller than expected on the basis of the spin echo experiments and shows that the existence of polarization-induced spin wave damping is an open question.

Perinatal risk factors for cranial ultrasound abnormalities in neonates born after spontaneous labour before 34 weeks.

OBJECTIVE: The aim of this study was to identify risk factors for cranial ultrasound abnormalities in neonates born after spontaneous preterm labour with or without prolonged premature rupture of the membranes (PROM). METHODS: The presence of intraventricular haemorrhage and cystic periventricular leucomalacia was investigated in a cohort of neonates born between 24 and 34 weeks using cranial ultrasound. A stepwise forward logistic regression was performed to analyse the influence of antenatal and postnatal variables on cranial ultrasound abnormalities. RESULTS: The study group consisted of 205 neonates and cranial ultrasound abnormalities were identified in 27 infants. Early onset neonatal infectious disease (OR 3.09, 95% CI 1.24--7.70, P=0.01) increased the risk for cranial ultrasound abnormalities. Gestational age at birth (OR 0.96, 95% CI 0.93--0.99, P=0.03) and a full course of antenatal steroids (OR 0.33, 95% CI 0.13--0.85, P=0.02) reduced the risk for cranial ultrasound abnormalities. CONCLUSION: Early onset neonatal infectious disease is an independent risk factor for cranial ultrasound abnormalities in the very preterm neonate born after spontaneous labour with or without PROM.

Perinatal risk factors for adverse neurodevelopmental outcome after spontaneous preterm birth.

OBJECTIVE: The aim of this study was to investigate to what extend perinatal factors contribute to the neurodevelopmental outcome in a group neonates born after spontaneous preterm labour with or without prolonged rupture of the membranes (PROM). METHODS: In a cohort of neonates born after the spontaneous onset of labour with or without PROM before 34 weeks of gestation a stepwise forward logistic regression was performed to analyse the influence of antenatal and postnatal variables on adverse outcome. Adverse neurodevelopmental outcome was defined as a Griffith's developmental score <85, cerebral palsy, a major disability or perinatal death associated with severe cerebral damage. RESULTS: The study group consisted of 185 neonates. Seven neonates died with severe cerebral damage. After a forward logistic regression analysis three factors appeared to have an independent influence: gestational age protected against an adverse outcome (odds ratio (OR) per day increase 0.95, 95% confidence interval (CI) 0.90-0.97) while abnormal cranial ultrasound (intraventricular haemorrhage and periventricular leucomalacia) (OR 6.33, 95% CI 2.16-18.52) and the need for a second course of antibiotics (OR 1.85, 95% CI 1.02-3.33) increased the risk for adverse outcome. Comparing the group with a normal neurodevelopmental outcome with those with cerebral palsy, cranial ultrasound abnormalities were independently associated with cerebral palsy (OR 48.75, 95% CI 11.78-201.76). CONCLUSION: The most important way of preventing neurological damage in infants is to increase gestational age at birth and to avoid the development of intraventricular haemorrhage and periventricular leucomalacia.

Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial.

OBJECTIVE: To test the hypothesis that prophylactic administration of clindamycin 2% vaginal cream can reduce the incidence of preterm birth in a high risk population. DESIGN: A multi-centre, randomised, double-blind, placebo-controlled trial. SETTING: Twelve city hospitals in The Netherlands. PARTICIPANTS: One hundred and sixty-eight women with a singleton pregnancy and a history of a spontaneous preterm delivery in the preceding pregnancy. INTERVENTIONS: Clindamycin 2% vaginal cream, or placebo cream, administered daily for seven days at 26 and 32 weeks of gestation. MAIN OUTCOME MEASURES: Spontaneous preterm birth at < 37 weeks, admission for threatened preterm labour, neonatal infectious morbidity. RESULTS: In the intention-to-treat analysis no difference was found in overall preterm birth between clindamycin and placebo (23% vs 18%, respectively). In the subgroup who completed the trial and administered all medication, more women delivered before 34 weeks in the clindamycin group (1.4% in the placebo vs 9.0% in the clindamycin group; P < 0.05). The length of admissions for threatened preterm labour did not differ. More infectious neonatal morbidity was seen in the clindamycin group (5/83 vs 0/85; P < 0.05). CONCLUSION: Clindamycin 2% vaginal cream given prophylactically to women with a spontaneous preterm birth in the preceding pregnancy did not prevent preterm delivery or reduce the number of admissions for threatened preterm labour. The neonatal infectious morbidity in the group treated with clindamycin was significantly higher and a major concern.

PIP: This multi-center, randomized, double-blind, placebo-controlled trial aimed to determine whether prophylactic administration of clindamycin 2% vaginal cream can reduce the incidence of preterm birth in a high risk population. A total of 168 eligible women attending the antenatal clinics of 12 hospitals in Netherlands participated in the study. Clindamycin 2% vaginal cream was administered to 83 women, and placebo cream to 85 women, daily for 7 days at 26 and 32 weeks of gestation. Results of the study showed no difference in the overall preterm birth between clindamycin (23%) and placebo (18%) in the intention-to-treat analysis. In the subgroup, which completed the trial and administered all medication, more women delivered before 34 weeks in the clindamycin group (9%) compared to the placebo group (1.4%). Moreover, occurrence of neonatal infectious morbidity was higher in the clindamycin group (5/83 vs. 0/85; P 0.05). In conclusion, clindamycin 2% vaginal cream given prophylactically to women with a spontaneous preterm birth in the preceding pregnancy did not prevent preterm delivery or reduce the number of admissions for threatened preterm labor.

Low-temperature polarized helium-3 for MRI applications.

The first 3He nuclear magnetic resonance (NMR) experiments using low-temperature prepolarization are presented. 3He cells were polarized at 4.2 K and 4.7 T, transported to another magnet, heated to room temperature, and used for NMR experiments at 2.35 T. Cells with and without a rubidium coating were tested. In both cases, the NMR signal was greater than 100 times the thermal equilibrium signal. No evidence of a rubidium coating effect on the longitudinal relaxation time T1 of 3He (500 mbar) at 4.2 K could be demonstrated. NMR gradient-echo images of the cells were acquired.

A prediction of DPP IV/CD26 domain structure from a physico-chemical investigation of dipeptidyl peptidase IV (CD26) from human seminal plasma.

Human DPP IV, isolated from seminal plasma by means of immobilised adenosine deaminase, occurs in different forms which are distinguishable by net charge and native molecular weight. Charge differences arise primarily from different degrees of glycosylation containing various amounts of sialic acid. The majority of DPP IV isolated from total seminal plasma consists of the extracellular part of the protein starting at Gly-31. It is a very stable protein resisting high concentrations of denaturant. Unfolding experiments under reducing conditions are indicative of the existence of at least two domains which function independently. One of these domains is highly stabilised by disulfide bonds. Disruption of the disulfide bonds does not affect the activity, the dimeric state nor the adenosine deaminase binding properties of the protein but renders it more susceptible to proteolysis. The low-angle X-ray scattering spectrum is consistent with a model for a protein containing two subunits, each composed of three domains linked by flexible regions with low average mass. The secondary structure composition, determined by FTIR spectrometry, indicates that 45% of the protein consists of beta-sheets, which is higher than expected from computed secondary structure predictions. Our results provide compelling experimental evidence for the three-domain structure of the extracellular part of DPP IV.

Gas chromatographic-mass spectrometric (GC-MS) analysis of gonadal steroids in plasma of the male African catfish, Clarias gariepinus: effects of castration or treatment with gonadotropin releasing hormone analogue.

To identify testicular steroids that may be involved in the feedback mechanisms of the hypothalamus-pituitary-gonad axis in African catfish, Clarias gariepinus, steroids, which are known to be produced by the testis in vitro, were identified and quantified in blood plasma before and after castration using gas chromatography followed by mass spectrometry. Before castration 20 testicular steroids were detected. Quantitatively dominant steroids were testosterone (16.9 +/- 4.3 ng/ml), androstenedione (12.0 +/- 3.9 ng/ml), and 11-ketotestosterone (6.7 +/- 1.8 ng/ml). After castration, only these steroids showed a strong decrease in plasma, indicating that they are of testicular origin. Assuming that steroids involved in the feedback to the pituitary are under gonadotropic control, fish were injected with two doses of a salmon gonadotropin releasing hormone analogue (sGnRHa). The lower sGnRHa dose (0.25 microgram/kg body weight) increased plasma GTH-II levels in the same range as those induced by castration, resulting in a significant increase in plasma levels of testosterone, androstenedione, and 11-ketotestosterone. After injection of a higher dose of sGnRHa (5.0 micrograms/kg body weight), there was a greater increase in plasma GTH-II level, as well as a significant increase in most of the other steroids studied. The decreased levels of testosterone, androstenedione, and 11-ketotestosterone after castration and the significant increase in these steroids following moderate GTH stimulation, suggest that one or more of these steroids plays a role in the feedback mechanism within the hypothalamus-pituitary-gonad axis.