The nucleus acts as a ruler tailoring cell responses to spatial constraints.

The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.

An observational study of the impact of a rehabilitation admission on readmission data.

BACKGROUND AND AIM: Specialist psychiatric rehabilitation services are changing in response to overall redesign of psychiatric services. The assumed therapeutic gains of these services have not been established or quantified, and their role in contemporary practice has not been formally articulated. The aim of this observational study is to examine the impact of an admission to psychiatric rehabilitation wards at the Royal Edinburgh Hospital on readmission data post-discharge. METHOD: Thirty-five admissions were included in the sample. Simple measures of outcome were used: the number of days spent in hospital; number of Mental Health Act uses; number of admissions. This information was obtained from case notes and from data collected routinely on the Patient Information Management System. These measures were examined in the two-year periods before and after a rehabilitation admission. RESULTS: In the two-year period following the index admission there was a significant reduction in all these measures compared to the two-year period before the index admission: mean number of bed days (p < 0.001); number of uses of the Mental Health Act (p < 0.001); number of readmissions (p < 0.01). CONCLUSION: There was an improvement in patient outcome measures following a rehabilitation admission.

Osteochondritis dissecans of the humeral capitellum. Diagnosis and treatment.

Elbow pain seen in the at-risk athlete, such as a baseball player (in particular, a pitcher) or gymnast, should raise suspicion for OCD. OCD of the humeral capitellum remains a difficult problem to treat. Once radiographic changes are obvious, long-term studies suggest that half of affected individuals will be symptomatic. Currently, the key to successful treatment is early detection. Gymnasts, in general, fare worse in returning to sport. The reason is not entirely clear but is likely related to the amount of force directed across the elbow and the nature of the sport. Pitchers sometimes can be returned, but to another position. Radiographs remain the screening test of choice but can give the surgeon a false sense of security, because changes early in the disease process may not be obvious radiographically. Views at 45 degrees flexion and contralateral elbow views are helpful. The advent of MR imaging now allows the practicing orthopaedic surgeon to assess very early lesions effectively that might otherwise be underappreciated on radiographs. With more advanced lesions, radiographic findings are more obvious and demonstrate the more classic capitellar fragment with a surrounding zone of lucency. MR imaging is this setting is helpful in assessing the overlying articular cartilage and, hence, the stability of the fragment. In the absence of obvious loose bodies or mechanical symptoms, rest is the first step in treatment. If symptoms persist, then operative intervention is indicated. About half of these patients heal with nonoperative treatment. Pretreatment assessment of fragment viability has not traditionally been incorporated into the treatment algorithm. Recent anecdotal evidence suggests that stability and viability of a fragment can be assessed using intravenous contrast. Knowledge of the fragment viability could allow those lesions likely to heal without surgical intervention to be distinguished from those requiring surgical intervention. The procedure should be chosen based on the size of the lesion and the integrity of the subchondral bone. Subchondral drilling and microfracture can only resurface defects and cannot reconstitute subchondral bone. Autologous chondrocyte implantation has limited ability to address subchondral bone loss, whereas autograft and allograft osteochondral transplantation can restore subchondral bone. Most authors would agree that there is no role currently for reduction and fixation of long-standing, free loose bodies. No consensus exists regarding acute dislodging of an in situ loose fragment. Long-term results after radiographic changes are present suggest a degenerative course in about half the patients. Whether the newer techniques of cartilage resurfacing will significantly impact the natural history of this process remains to be seen.

The N-methyl-D-aspartate receptor, synaptic plasticity, and depressive disorder. A critical review.

The roles of the N-methyl-D-aspartate (NMDA) receptor and NMDA receptor-mediated synaptic plasticity are reviewed in the context of depressive disorder and its treatment. The mode of action of antidepressant treatment is poorly understood. Animal studies have suggested that many antidepressant drugs show activity at the NMDA receptor and that NMDA antagonists have antidepressant profiles in preclinical models of depression. A post-mortem study in humans has suggested that certain binding characteristics of the NMDA receptor may be down-regulated in the brains of suicide victims. "Depressogenic" stressors in animals and chronic administration of antidepressant agents perturb NMDA-dependent synaptic plasticity in the hippocampus.

Surgical treatment of combined injury to anterior cruciate ligament, posterior cruciate ligament, and medial structures.

Injuries involving the anterior cruciate, posterior cruciate, and medial collateral ligaments represent one combination of injuries representing knee dislocation. Prompt reduction and neurovascular evaluation are necessary when treating these injuries. Operative management involving reconstruction and repair of the injured structures produces optimal results. This article outlines the principles involved in evaluating and managing these injuries, combined with specifics of the authors' treatment approach, and review of the literature.

Transient translocation of the B cell receptor and Src homology 2 domain-containing inositol phosphatase to lipid rafts: evidence toward a role in calcium regulation.

Membrane microdomains (lipid rafts) are enriched in selected signaling molecules and may compartmentalize receptor-mediated signals. Here, we report that in primary human B lymphocytes and in Ramos B cells B cell receptor (BCR) stimulation induces rapid and transient redistribution of a subset of engaged BCRs to lipid rafts and phosphorylation of raft-associated tyrosine kinase substrates. Cholesterol sequestration disrupted the lipid rafts, preventing BCR redistribution, but did not inhibit tyrosine kinase activation or phosphorylation of mitogen-activated protein kinase/extracellular regulated kinase. However, raft disruption enhanced the release of calcium from intracellular stores, suggesting that rafts may sequester early signaling events that down-regulate calcium flux. Consistent with this, BCR stimulation induced rapid and transient translocation of the Src homology 2 domain-containing inositol phosphatase, SHIP, into lipid rafts.

Total knee arthroplasty for chronic posterior knee dislocation: report of 2 cases with technical considerations.

This article reports our experience in 2 patients with chronic knee dislocations treated with total knee arthroplasty, focusing on the technical difficulties in obtaining a well-balanced, well-aligned knee.

Metal-backed patellar component failure in total knee arthroplasty: a possible risk for late infection.

Between 1985 and 1987, 1837 primary total knee arthroplasty (TKA) prostheses were implanted in 1503 patients. Group I included 843 knee with metal-backed patellar components (MBPC), and group II included 994 knees with all polyethylene patellar components (APPC). Follow-up averaged 5.7 years (range, 2 to 11 years). Twenty-four MBPC (2.9%) and 16 APPC TKA cases (1.6%) developed deep infection. In the time interval between arthroplasty and 2-year follow-up, eight MBPC and 11 APPC knees developed deep periprosthetic infection. The difference in the cumulative probability of infection between the two groups during this time interval was not significant (relative risk, 0.9; 95% confidence interval [CI], 0.3-2.1; P = 0.73). However, after the 2-year follow-up, 16 MBPC and 5 APPC knees developed late infection, and the difference in the cumulative probability of infection between the MBPC and APPC knees during this time interval was significant (relative risk, 3.1; 95% CI, 1.1-8.5; P = 0.02). Although the mechanism for this increased risk of these late infections is not well understood, the attendant synovitis, effusion, and relative hyperemia of these knees in the presence of the particulate metal and polyethylene debris may increase the potential of bacterial seeding to these prostheses. Particulate metal debris has been previously shown to suppress bacterial phagocytosis and may play a role in the pathogenesis of these infections. We propose that the presence of metal-backed patellar failure represents a "prosthesis at risk" for the development of late prosthetic infection.

The use of oxytocin.

Synthetic oxytocin offers a safe and effective means of producing regular uterine activity and has a fairly large therapeutic index; however, the mild antidiuretic and vasoactive properties of oxytocin increase the risk of water intoxication and hypotension. The issue of reduction in cesarean section rates through the use of an active management protocol is being studied actively in the United States and Canada at this time. The authors recommend infusion protocols for the augmentation and induction of labor that use low doses of dilute oxytocin, increased at intervals no more than 40 minutes. Pharmacokinetic and clinical studies support the use of oxytocin in the physiologic range as efficacious and prudent. The longer induction to delivery time demonstrated by some, but not all authors, in our opinion, is a reasonable alternative to avoidable uterine hyperstimulation with the potential for fetal and maternal injury. We advocate the use of the lowest dose necessary to produce adequate uterine contractility and cervical change.

Oxytocin to induce labor.

Oxytocin is a highly successful and safe agent for inducing labor and has a fairly large therapeutic index. It has, however, minimal, but not trivial, antidiuretic and vascular activity when used in large doses. Therefore, to induce labor, low-dose oxytocin dosing regimens that produce efficacious uterine activity and avoid side effects are recommended. Oxytocin should be used in the lowest possible doses necessary to effect a clinical response. Diligence must be exercised when monitoring labor and fetal well-being. Hofbauer, the first to use oxytocin to induce labor, said in 1927 that oxytocin, "with its power of producing regular, rhythmical and forcible uterine contractions, should be regarded as a most beneficent and valuable agent, which, however, should always be employed with care and a realisation of its limitations and dangers." His words remain valid today.

Physical activity, but not aerobic capacity, correlates with back strength in healthy premenopausal women from 29 to 40 years of age.

The correlation of muscle strength at various sites of the axial and appendicular skeleton with physical activity and aerobic capacity was assessed in women 29 to 40 years old. Muscle strength of the spine and upper extremities was determined with strain gauges in 96 healthy white women, and power grip was used as an indicator of upper extremity strength. The physical activity score, which reflected the level of daily weight-bearing activity and was based on a standardized scale, ranged from 3 to 15. Maximal oxygen uptake (aerobic capacity) was measured in 69 of the 96 subjects. The mean values for maximal oxygen uptake were 1.9 liters/min and 27.9 ml/kg per minute when normalized for weight. In general, muscle strength was significantly correlated between axial and appendicular sites; thus, the axial musculature usually represents overall muscle strength. Maximal oxygen uptake in milliliters per kilogram per minute was not correlated with back extensor strength or upper extremity strength. Physical activity score was significantly correlated with back extensor strength but not with maximal oxygen uptake (aerobic capacity) either in liters per minute or in milliliters per kilogram per minute. Thus, maximal oxygen uptake is an invalid marker for level of daily weight-bearing physical activity.

Use of the fetal chest in estimating fetal weight.

OBJECTIVE: This study was designed to develop formulas using the chest circumference instead of the abdominal circumference for estimating fetal weight. STUDY DESIGN: Ultrasonographic measurements of the chest circumference, biparietal diameter, abdominal circumference, humeral length, and femoral length were obtained in 75 term fetuses of uncomplicated pregnancies within 24 hours of delivery. Three equations for fetal weight estimation that used the chest circumference, instead of the abdominal circumference, in combination with the biparietal diameter or the humeral length were developed by regression analysis. RESULTS: The average mean errors of fetal weight estimation for these equations vary from 7.1% to 7.6%. CONCLUSIONS: These equations may be used in predicting the birth weight when the fetal abdomen is altered by certain fetal abnormalities.

Laparoscopic cholecystectomy during pregnancy.

There is a strong association between pregnancy and gallstones. When acute cholecystitis or recurring bouts of biliary colic occur during pregnancy, medical therapy is usually initiated but occasionally fails. Laparoscopic cholecystectomy has recently been described for the treatment of symptomatic cholelithiasis, but many authors consider pregnancy to be an absolute contraindication to this operation. We herein describe the management of markedly symptomatic cholelithiasis during the second trimester of pregnancy using laparoscopic techniques in five patients. Tocolytic medications were administered perioperatively in two patients, and open laparoscopy or the use of an alternative site for insertion of the initial port was used in all patients. Laparoscopic cholecystectomy without cholangiograms was successful in all five patients and postoperative hospitalization ranged from 24 to 48 h. Uncomplicated term delivery has occurred in three of the five patients; in the other two patients, normal pregnancies are continuing. Laparoscopic cholecystectomy can be performed safely during pregnancy, as long as the patient is monitored carefully and specific precautions are observed.

Noninvasive fetal ECG mode fetal heart rate monitoring by adaptive digital filtering.

Beat-to-beat variability (BTBV) of the fetal heart rate (FHR) is considered an indication of the neural integrity and is an important prognostic indicator of fetal well-being. We report the initial evaluation of a recently developed abdominal fetal ECG (AFECG) mode of FHR monitoring using Adaptive Digital Filtering (ADF) to accurately obtain BTBV noninvasively. Five women in labor at term were monitored with the direct fetal scalp electrode (FSE) and simultaneously with the AFECG using ADF. A computer analysis of 3298 seconds (55 minutes) of data provided a one-to-one comparison of the R-R intervals. One analysis of the direct FSE data with a second simultaneous analysis from the same electrode, to serve as control, was compared with the noninvasive AFECG data. The study group has a standard deviation of only 1.50 bpm compared to 0.79 bpm for the control group. The AFECG method agrees with the direct FSE method within 1 bpm for 92.6% of the reported R-R intervals and within 2 bpm for 98.9% of the reported intervals. This new noninvasive AFECG technique with ADF provides a continuous record of instantaneous FHR and BTBV that may be relied upon to provide an accurate continuous clinical record. The reliability of the technique has yet to be determined over a wide range of subjects.

Receptor-mediated endocytosis of testicular transferrin by germinal cells of the rat testis.

The present study examines events of the Sertoli cell iron delivery pathway following the secretion of diferric testicular transferrin (tTf) into the adluminal compartment of the rat seminiferous epithelium. The unidirectional secretion of tTf by Sertoli cells was verified, in vivo, and it was shown that this protein is internalized by adluminal germ cells. It was further determined by Scatchard analysis that this internalization was mediated by high affinity transferrin binding sites on the surface of round spermatids, numbering 1453/cell and displaying a Kd = 0.6 x 10(-9) M. Northern blot analysis of RNA isolated from adluminal germ cells, namely spermatocytes, round spermatids and elongating spermatids, indicated that these cells expressed Tf receptor mRNA and ferritin mRNA in levels inversely related to their stage of maturation. Finally it was determined that following binding and internalization in round spermatids, Tf became associated with the endosomal compartment and was recycled back to the cell surface. This study illustrates the immediate fate of tTf once it is secreted by the Sertoli cells. Thus, diferric tTf binds of Tf receptor on the surface of adluminal germ cells, is internalized by receptor-mediated endocytosis and the apoTf-Tf receptor complex is recycled back to the cell surface where apotTf is released into the adluminal fluid.

Magnesium tocolysis and neonatal bone abnormalities: a controlled study.

This study was conducted to investigate the relationship between maternal administration of intravenous (IV) magnesium sulfate and radiographic abnormality of neonatal long bones. Eleven neonates in the exposed group were born to mothers who had received IV magnesium tocolysis for more than 7 days. Two gestational age-matched unexposed neonates were selected for each member of the exposed group. Initial chest radiographs of exposed and unexposed neonates were reviewed in random sequence by a pediatric radiologist who was blinded to exposure status. On evaluation of the proximal humeri, six neonates had radiographic abnormalities consisting of transverse radiolucent and/or sclerotic bands; all six were in the exposed group. The difference in radiographic findings between the exposed and unexposed groups was statistically significant (P less than .001). These results support the existence of a causal relationship between prolonged IV magnesium tocolysis and abnormal fetal bone mineralization. Further study is needed to elucidate the mechanism and clinical significance of these bone changes.

Acute fatty liver of pregnancy associated with preeclampsia: management of hepatic failure with postpartum liver transplantation.

Acute fatty liver of pregnancy is a potentially fatal disorder. We report a patient complicated by preeclampsia, coagulopathy, encephalopathy, and hepatorenal syndrome successfully managed by postpartum hepatic transplantation.