Did implementation of three ligament tenodesis improve patient outcome after chronic scapholunate instability? A retrospective study.

INTRODUCTION: Scapholunate instability frequently leads to chronic pain or even severe osteoarthritis of the wrist. Most favored reconstruction techniques of chronic SL-ligament injuries are based on the usage of a tendon, although there is still a lack of consensus which technique is superior. MATERIALS AND METHODS: In a retrospective cohort analysis we compared 9 patients who underwent SL-ligament repair according to Van den Abbeele and 12 patients who underwent modified three ligament tenodesis according to Garcia-Elias, performed at a single institution. RESULTS: Follow-up of Van den Abbeele group was 36-120 months and 13-39 months in the Garcia Elias cohort. Although both techniques showed good functional outcome in most cases, modified three ligament tenodesis seemed to be advantageous regarding wrist range of motion (162°) compared to Van den Abbeele cohort (87°). Moreover, pain score showed significant differences between the two cohorts during follow up (VAS Van den Abbeele 4.2; VAS Garcia Elias 1.7). Interestingly, DASH-score (16.1 Van den Abbeele; 16.8 Garcia Elias) and modified mayo wrist score (72 Van den Abbeele; 69 Garcia-Elias) did not show any differences between the two patient cohorts. CONCLUSIONS: Via implementation of modified three ligament tenodesis as a standard of care for our patients we could improve the functional outcome after SL-ligament injuries and effectively decrease postoperative pain.

Optimizing remote ischemic conditioning (RIC) of cutaneous microcirculation in humans: Number of cycles and duration of acute effects.

OBJECTIVE: Non-invasive Remote Ischemic Conditioning (RIC) offers an approach to reduce tissue damage in various organs/tissues. Besides attenuation of Ischemia-Reperfusion injury (I/R), beneficial effects on cutaneous microcirculation of free microsurgical flaps have been reported. Given the recency of this technique, there are considerable gaps in the current understanding of its mechanism of action. As a result, clinical transfer of RIC is prolongated in several fields. We aimed to optimize the RIC protocol by examination of different RIC-cycle numbers and its effect on changes of cutaneous microcirculation and duration. METHODS: 80 subjects were divided into groups (1, 3, 5, 7 RIC cycles). RIC was applied via an inflatable tourniquet. Cutaneous microcirculation was continuously assessed at the contralateral anterior lateral thigh utilizing a ©O2C-device continuously. RESULTS: RIC caused significant and sustained changes in microcirculation. Four hours after completion of RIC, a maximum increase of +80.8% (CI 1.395-2.221) in blood flow and +23.5% (CI 1.098-1.372) in tissue oxygen saturation was measured (three-cycle group). A higher number of applied cycles was accompanied with significant higher mean pain. CONCLUSION: Acute improvement of cutaneous microcirculation due to RIC lasted for at least 4 h after completion of the RIC-protocol. Dose-dependent effects of RIC are likely. With regard to the increase in pain, we recommend a RIC protocol of 3 cycles for future clinical application.

[Regulation of bone metabolism by the Wnt signaling pathway]. / Regulation des Knochenstoffwechsels durch den Wnt-Signalweg.

The development and homeostasis of multicellular organisms depends on a complex cellular interaction between proliferation, migration, differentiation, adhesion, and cell death. Wnt signaling pathways coordinate these different cellular responses. Wnt signaling plays a role as a regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. The Wnt signaling pathway is an attractive therapeutic target with the potential to directly modulate stem cells responsible for the regeneration of skeletal tissue. Recent studies indicate that Wnt ligands are capable of promoting bone growth, suggesting that Wnt factors could be used to stimulate bone healing in osteogenic disorders.

Myostatin serum concentration as an indicator for deviated muscle metabolism in severe burn injuries.

INTRODUCTION: Patients experiencing thermal injuries with an extent of over 20% of total body surface area suffer from systemic catabolic disease. The thermal trauma-induced loss of muscle mass causes a higher incidence for comorbidities and subsequently a higher mortality. In this study, we aimed to investigate the role of myostatin in the interplay with follistatin during muscle cachexia. METHODS: Patients with burn injuries (>10% total body surface area) between the ages of 18 and 75 were prospectively included within the first 48 h after trauma to determine deviations of parameters connected to muscle catabolism. In the chronic state of burn injury (9-12 months after trauma), we re-evaluated myostatin and follistatin concentrations as well as muscle strength of the non-dominant forearm. RESULTS: We were able to show a time-dependent alteration (9-12 months after burn injury) of myostatin with an initial decrease (p < 0.001) and long-term increase (p < 0.001) after thermal injury in blood serum. For follistatin, a reciprocal correlation was observed (r = -0.707, p = 0.001). Accordingly, muscle strength of the non-dominant hand and forearm was significantly decreased 9-12 months after injury in post-burn patients compared with healthy patients with a significant correlation to myostatin levels (r = -0.899, p < 0.001). In addition, initial myostatin serum concentration was predictive for long-term muscle strength impairment. CONCLUSION: With regard to the muscle metabolism after thermal trauma, our data suggest an acute anabolic response, presumably to spare muscle mass, which is converted to catabolic conditions accompanied by muscle strength reduction in the chronic phase. Myostatin plays a crucial role in this orchestration and initial myostatin concentration may predict the long-term muscle strength.

The effect of fenofibrate on HDL cholesterol and HDL particle concentration in postmenopausal women on tibolone therapy.

BACKGROUND: Low high-density lipoprotein (HDL) cholesterol and particle concentration are risk factors for coronary heart disease in women. Tibolone lowers HDL cholesterol and HDL particle concentration, an effect that could be reversed by the peroxisome proliferator-activator receptor-α agonist fenofibrate. OBJECTIVE: To assess the effects of fenofibrate on plasma HDL particles in postmenopausal women taking tibolone therapy. DESIGN AND PARTICIPANTS: Randomized crossover study conducted in a women's health clinic. Fourteen postmenopausal women taking tibolone 2.5 mg daily for menopausal symptoms were randomized to either fenofibrate 160 mg daily or no treatment for 8 weeks, followed by a 3-week wash-out for fenofibrate and then crossed over to alternate therapy for another 8 weeks. The main outcome measure was changes in plasma HDL cholesterol concentration, apoA-I and apoA-II, LpA-I and LpA-I-A-II. RESULTS: After 8 weeks of fenofibrate therapy, there was no change in HDL cholesterol, 1.13 ± 0.06 v 1.16 ± 0.06 mmol/l (P = 0.47) or apoA-I, 1.19 ± 0.05 v 1.20 ± 0.05 g/l (P = 0.23). LpA-I fell significantly 0.35 ± 0.03 v 0.29 ± 0.02 (P = 0.02) but there was a rise in apoA-II, 0.35 ± 0.01 v 0.39 ± 0.01 g/l (P = 0.01). There was a significant fall in total cholesterol, triglycerides, low-density lipoprotein cholesterol and apoB. CONCLUSION: In women taking tibolone, fenofibrate increases plasma apoA-II concentration and effects a redistribution of HDL subfractions but does not correct tibolone-induced changes in HDL cholesterol or HDL particle concentration. The mechanism and significance of this require further investigation.

The proform of eosinophil major basic protein: a new maternal serum marker for Down syndrome.

The proform of eosinophil major basic protein (proMBP), the most abundant protein in the eosinophil specific granule, is synthesized by the placenta and secreted into the maternal circulation, where it is found complex-bound to pregnancy-associated plasma protein-A (PAPP-A) and other proteins. We examined the potential of proMBP as a maternal serum marker for fetal Down syndrome (DS) by determining its maternal serum concentration (MSpMBP) in 25 Down syndrome (DS) pregnancies and 152 control pregnancies in the first trimester, and in 105 DS pregnancies and 156 control pregnancies in the second trimester. The median (95 per cent confidence interval) MSpMBP MoM in DS pregnancies (n=15) was 0.66 (0.49-0.79) in gestational weeks 5-9; 1.06 (0.71-1.97) in weeks 10-12 (n=10) and 1.62 (1.18-1.98) in weeks 14-20 (n=105). Using parameterized receiver operator characteristics analysis for proMBP as a single marker for DS, detection rates (DRs) of 22 per cent and 38 per cent, for false-positive rates (FPRs) of 5 per cent, were found in weeks 5-9 (using MSpMBP/=cut-off), respectively. When age and MSpMBP were used as markers in combination, a DR of 36.8 per cent for an FPR of 5.5 per cent was obtained in weeks 5-9 using a risk cut-off of 1:250. In weeks 14-20 the DR was 48.4 per cent for an FPR of 5.3 per cent using the same risk cut-off. This makes proMBP a marker comparable in diagnostic efficiency to human chorionic gonadotrophin (hCG), and exceeding that of alpha-fetoprotein (AFP) and unconjugated oestriol (uE3), in the second trimester.

Polymorphic eruption of pregnancy and herpes gestationis: comparison of granulated cell proteins in tissue and serum.

Polymorphic eruption of pregnancy (PEP) and herpes gestationis (HG) are pregnancy-related dermatoses of unknown aetiology with eosinophil infiltration which, at early stages, may show similar clinical and histopathological features. To determine the relative contributions of eosinophils, neutrophils and mast cells to the pathogenesis of PEP and HG through deposition of granule proteins, we studied tissue and serum from 15 patients with PEP and 10 with HG. Using indirect immunofluorescence with antibodies to human eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), neutrophil elastase and mast cell tryptase, we determined and compared cellular and extracellular staining patterns in lesional skin biopsy specimens and, using immunoassay, measured MBP, EDN, and ECP in patients' sera. Eosinophil infiltration and extracellular protein deposition of all three eosinophil granule proteins were present in both PEP and HG indicating a pathogenic role for eosinophils in both diseases. Staining for eosinophil granule proteins was especially prominent in urticarial lesions and around blisters in HG. EDN and ECP serum levels in PEP and ECP serum levels in HG were significantly increased compared with those in normal pregnant and normal nonpregnant serum. Neutrophils were more prominent in HG specimens than in PEP specimens; extracellular neutrophil elastase was minimally present and similar in both diseases. Mast cell numbers and extracellular tryptase deposition did not differ between the two diseases and did not differ from mast cell counts in skin of normal pregnant women. This study shows that eosinophil granule proteins are deposited extracellularly in tissue and are increased in serum in both PEP and HG. Moreover, eosinophil involvement in the two diseases is more consistent than neutrophil and mast cell involvement. Comparatively, tissue eosinophil infiltration and extracellular protein deposition is more extensive in HG than in PEP, suggesting that eosinophil involvement is greater in the pathogenesis of HG than PEP and similar to that found in bullous pemphigoid.

A citogenética do espermatozóide humano: técnica de fertilizaçäo in vitro, heteróloga, homem/hamster / Cytogenetics of human spermatozoa: human/hamster in vitro fertilization technique

A constituiçäo cromossômica do espermatozóide humano pode ser estudada, atualmente, através da técnica de fertilizaçäo "in vitro" (FIV), heteróloga, homem/hamster. Essa técnica permite a individualizaçäo dos cromossomos do espermatozóide humano, possibilitando a análise de suas anomalias numéricas e estruturais. O aprimoramento dessa técnica estimulou um novo campo de pesquisa na Citogenética Humana e na Genética Clínica. Sua implantaçäo em nosso laboratório na Faculdade de Medicina de Ribeiräo Preto, Universidade de Säo Paulo, propiciará melhor estimativa da probabilidade de transmissäo de anomalias cromossômicas por células de linhagem germinativa de homens em risco genético.

Eosinophil infiltration and degranulation in normal human tissue.

Localization of eosinophil granule major basic protein by immunofluorescence permits recognition of both eosinophil infiltration and degranulation. Over the past decade and a half, our laboratory has shown that eosinophil infiltration and degranulation occur in many diseased tissues in humans; among normal tissues studied as controls, only the gut showed striking eosinophil infiltration and degranulation. Using an indirect immunofluorescence procedure for the detection of major basic protein, we extended our analyses of normal human tissues to include tissues from essentially all body organs; a total of 117 biopsy/autopsy specimens were analyzed. To determine whether the method of tissue procurement affected the level of eosinophil degranulation in the normal gastrointestinal tract, normal proximal jejunum from six patients was biopsied using either an endoscopic forceps or a scalpel at the time of elective surgery and examined by immunofluorescence. Spleen, lymph node, and thymus tissues showed eosinophil infiltration with scant evidence of degranulation, but the only organ showing both eosinophil infiltration and remarkable degranulation was the gastrointestinal tract. Eosinophil degranulation was significantly increased in specimens obtained by endoscopic forceps compared to those obtained by scalpel (P = 0.021). These results indicate that tissue procurement methods affect the degree of eosinophil degranulation in the gut. Thus, among normal human body organs, both eosinophil infiltration and appreciable degranulation consistently occur only in the gut.

[Claude Bernard-Horner syndrome and its opposite, Pourfour du Petit syndrome, in anesthesia and intensive care]. / Le syndrome de Claude Bernard-Horner et son contraire, le syndrome de pourfour du petit, en anesthésie-réanimation.

OBJECTIVE: To analyse cases of Horner's syndrome (HS) and its opposite, Pourfour du Petit's syndrome (PPS), occurring in anaesthesia and intensive therapy with consideration of the data of current literature. DATA SOURCES: For this paper we have reviewed the French, English and German literature published in anaesthesia and intensive care journals using Medline search and the current textbooks. STUDY SELECTION: All observational studies on these syndromes, whether clinical cases or letters to the editor, form the basis for this article. DATA EXTRACTION: The articles were analysed mainly with regard to diagnosis, therapy and prognosis of syndromes due to iatrogenic causes. DATA SYNTHESIS: HS is caused by a paralysis of the ipsilateral sympathetic cervical chain and includes a ptosis of the upper eyelid, a slight elevation of the lower lid, a sinking of the eyeball, a constriction of the pupil, a narowing of the palpebral fissure, a nasal stuffiness associated with anhidrosis, and flushing of the affected side of the face. Regional anaesthesia (intra-oral anaesthesia, brachial plexus block, epidural anaesthesia whether by thoracic, lumbar or caudal approach, as well as interpleural analgesia) is the main anaesthetic cause for HS. HS due to the effect of a local anaesthetic is transient, it can precede a high spinal block and a cardiovascular collapse. HS from puncture of the internal jugular vein is most often permanent. When transient, HS regresses within 3 months after puncture. Other causes of HS include intraoperative posture, pleural drain, neck surgery, neck trauma. A mydriatic collyrium, such as phenylephrine, resolves ptosis for less than 1 hour and results in blurred vision from pupillary dilation. Major ptosis requires surgery. PPS is the reciprocal HS and is caused by a stimulation of the ipsilateral sympathetic cervical chain. PPS can precede HS. It carries a risk for conjunctivitis, keratitis and epiphora in case of major exophthalmia. PPS is often reported as an unilateral mydriasis. PPS has the same causes as HS. Myotic collyriums are relatively inefficient. Major lid retraction requires a tarsorraphy, pomades and nocturnal lid occlusion. A part of HS and most PPS occurring in anaesthesia and intensive care remain unrecognized or are recognized with delay, especially if they remain minor and transient or when they occur in unconscious patients, in horizontal posture.

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Paracoccidioidomycosis is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Although eosinophils have long been associated with the immune defense against helminths, the role of eosinophils in the immune response to fungal diseases is not as well studied. The eosinophil granule major basic protein is toxic to helminths and mammalian cells in vitro, and its release has been used as a marker of eosinophil localization and degranulation. To determine whether eosinophil infiltration and degranulation, as evidenced by the deposition of major basic protein, occur in lesions of P. brasiliensis, we used an immunofluorescence technique to localize the P. brasiliensis organisms and eosinophils and major basic protein. Initially, all tissues were stained with polyclonal antibody to major basic protein; subsequently, colocalization of major basic protein and P. brasiliensis by double staining with mouse and rabbit antibodies, respectively, was performed. Nine biopsy tissues from seven patients were analyzed. All nine biopsies showed infiltration of intact eosinophils using both the monoclonal and the polyclonal anti-major basic protein antibodies, along with the presence of P. brasiliensis. Furthermore, using the polyclonal anti-major basic protein antibody, nine of nine tissues showed extracellular major basic protein deposition (granular or diffuse fluorescence staining outside of intact eosinophils). The double staining procedure using the anti-major basic protein monoclonal antibody showed extracellular deposition in five of eight biopsies; in these five biopsies, approximately 60% of the areas containing P. brasiliensis had extracellular major basic protein deposited on the organisms. These observations support the hypothesis that the eosinophil, through toxic granule proteins such as major basic protein, participates in the pathophysiology of paracoccidioidomycosis.

Localization of eosinophil-derived neurotoxin and eosinophil cationic protein in neutrophilic leukocytes.

Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are generally regarded as eosinophil-specific proteins. We tested whether EDN and ECP are present in mature neutrophils. By indirect immunofluorescence, both eosinophils and neutrophils stained with antibodies to EDN and ECP. Lysates of purified (<0.1% eosinophil contamination) neutrophils contained EDN, 112+/-4 ng/10(6) cells, and ECP, 163+/-2 ng/10(6) cells, whereas eosinophil major basic protein (MBP) was not detectable. Electron microscopic examination of immunogold-labeled buffy coat cells stained with EDN antibody showed that EDN is localized to neutrophil granules. Finally, EDN mRNA was detected in lysates of highly purified neutrophils (0.001% eosinophil contamination) by the reverse transcription-polymerase chain reaction. We conclude that proteins that are either identical to or immunologically cross-reactive with EDN and ECP are present in neutrophils and that EDN is synthesized and localized to neutrophil granules. Thus, caution must be exercised in interpreting the presence of EDN and ECP as specific markers of eosinophil-associated inflammation in human disease.

Placental site trophoblastic tumor: human placental lactogen and pregnancy-associated major basic protein as immunohistologic markers.

Placental site trophoblastic tumor (PSTT) consists of a neoplastic proliferation of intermediate or extravillous trophoblast (also known as X cells). Pregnancy-associated major basic protein (pMBP) is a marker for placental intermediate trophoblast. We compared the distribution of pMBP and human placental lactogen (hPL) in 24 PSTT and 3 exaggerated placental site (EPS) specimens using two distinct immunohistologic methods. Statistical analyses were used to compare staining intensities in metastatic and nonmetastatic lesions. By immunofluorescence, 77% of the PSTT specimens and 100% of the EPS specimens stained with antibodies to pMBP, and the pMBP was localized in intermediate trophoblast and surrounding extracellular areas. By immunohistochemistry, 78% of the PSTT specimens and 100% of the EPS specimens stained for pMBP with a pattern comparable with that of immunofluorescence. Likewise, by immunohistochemistry, hPL stained 96% of the PSTT specimens and 100% of the EPS specimens. Immunohistochemical staining intensities for pMBP and hPL correlated (r2 = +.24; P = .013), but hPL staining was mainly confined to intermediate trophoblast and was more intense. Anti-pMBP tended to stain metastatic PSTT weakly. Thus, pMBP is a useful marker for intermediate trophoblast tumors and could help distinguish these from other forms of trophoblastic disease.

Major basic protein as a marker of malignant potential in trophoblastic neoplasia.

OBJECTIVE: We tested whether serum pregnancy-associated major basic protein levels distinguish between benign and malignant trophoblastic disease. STUDY DESIGN: We compared serum pregnancy-associated major basic protein levels in seven patient groups: nonpregnant and pregnant controls, partial moles, complete moles, persistent moles, placental-site trophoblastic tumors, and choriocarcinoma. RESULTS: The results showed that patients with partial and complete moles had elevated serum pregnancy-associated major basic protein levels comparable to normal pregnancy. In contrast, patients with persistent mole, placental-site trophoblastic tumors and choriocarcinoma had low median serum levels comparable to those of the nonpregnant controls. Significant differences were shown between the complete and persistent mole groups (p = 0.0001) and between the complete mole group and the choriocarcinoma group (p = 0.0001); however, persistent moles were indistinguishable from choriocarcinoma (p = 0.2010). CONCLUSION: Serum pregnancy-associated major basic protein levels thus distinguish between benign disorders, such as pregnancy and partial and complete moles, and trophoblastic tumors, such as persistent moles and choriocarcinoma. The absence of elevated serum levels of pregnancy-associated major basic protein may be useful clinically to indicate a more aggressive or frankly malignant tumor.

Allergen challenge in asthma: association of eosinophils and lymphocytes with interleukin-5.

To test whether eosinophil recruitment after pulmonary allergen challenge is associated with interleukin (IL)-5 in patients with asthma, we performed segmental bronchoprovocation (SBP) with saline, and with low and high dosages of ragweed extract in six patients with allergic asthma. Bronchoalveolar lavage (BAL) of the challenged segments was performed 5 min after challenge (immediate BAL fluid) and repeated 24 h later (late BAL fluid). Allergen challenge resulted in recruitment of eosinophils, and increased levels of eosinophil-active cytokines. A bioassay showed the predominant eosinophil-active cytokine in the late BAL fluids to be IL-5. Analysis of the late BAL fluids revealed that IL-5 levels correlated with the numbers of eosinophils and lymphocytes. This study provides evidence that IL-5 is a critical cytokine associated with eosinophil and lymphocyte recruitment into the airways of patients with asthma following exposure to allergen.

Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma.

In sera from pregnant women, pregnancy-associated plasma protein-A (PAPP-A) circulates as a disulfide-bound complex (approximately 474 kDa) with the proform of eosinophil major basic protein (proMBP) (Oxvig, C., Sand, O., Kristensen, T., Gleich, G. J., and Sottrup-Jensen, L. (1993) J. Biol. Chem. 268, 12243-12246). We have produced monoclonal antibodies (mAbs) against the PAPP-A.proMBP complex and established a radioimmunoassay utilizing a mAb recognizing the PAPP-A subunit. Surprisingly, serum levels of proMBP exceed those of PAPP-A four to 10-fold on a molar basis throughout pregnancy. This result prompted an investigation of the status of proMBP in pregnancy. Using a proMBP-specific mAb two novel proMBP complexes have been isolated by chromatographic techniques. Based on sequence analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and reaction with specific antibodies, one is shown to be a 2:2 disulfide-bound complex (approximately 200 kDa) between proMBP and angiotensinogen. The other is a 2:2:2 complex (approximately 300 kDa) between proMBP, angiotensinogen, and complement C3dg. Circulating proMBP in pregnancy is thus present in three types of complexes. These results suggest that specific interactions between the complexed proteins occur in pregnancy, and the possibility is raised that their interactions are important in the pathophysiology of pregnancies associated with hypertension.

Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta.

BACKGROUND: The human eosinophil granule major basic protein (MBP), a 13.8 kilodalton cationic polypeptide constituting the core of the eosinophil granule, is cytotoxic to parasites and numerous mammalian cells. Concentrations of a molecule immunochemically similar to eosinophil granule MBP are present in maternal plasma, and MBP mRNA has been localized to placental X cells by in situ hybridization. Eosinophil granule MBP is initially translated as a nontoxic precursor (proMBP), containing a 9.9 kilodalton acidic pro-portion that is believed to neutralize MBP toxicity. Recent analyses of sera from pregnant women have revealed that pregnancy-associated plasma protein-A (PAPP-A), previously thought to be a homotetramer of PAPP-A subunits, is actually composed of PAPP-A subunits bound by disulfide bonds to equimolar amounts of proMBP molecules to form a complex, PAPP-A/proMBP. In addition, the PAPP-A subunit nucleotide and deduced amino acid sequence have been determined from cloned cDNA. The PAPP-A monomer found in plasma contains 1547 amino acid residues. EXPERIMENTAL DESIGN: Because of the new evidence that PAPP-A is complexed with proMBP, previous studies on the localization of PAPP-A using antibodies to PAPP-A must be questioned. To determine the localization of the PAPP-A subunit, immunofluorescence was performed on normal placental tissues using proMBP absorbed anti-PAPP-A antibody. Furthermore, the expression of PAPP-A mRNA was investigated by in situ hybridization. RESULTS: Immunofluorescence staining with proMBP absorbed anti-PAPP-A antibody showed that PAPP-A is localized to placental septa, anchoring villi, and the syncytia of chorionic villi, whereas MBP is localized only to septa and anchoring villi. By in situ hybridization, PAPP-A mRNA is detected in placental X cells and syncytiotrophoblasts, but MBP mRNA is localized only to placental X cells. CONCLUSIONS: The presence of PAPP-A mRNA and PAPP-A subunit protein in placental X cells and syncytiotrophoblasts indicates that both X cells and syncytiotrophoblasts synthesize the PAPP-A subunit, whereas only X cells synthesize proMBP.

Pregnancy-associated major basic protein: deposition of protein and expression of mRNA at the maternal-fetal junction in early and late gestation.

Pregnancy-associated major basic protein (pMBP) has previously been isolated from human placenta and localized to the X cell. Here we used immunofluorescence staining and in situ hybridization to determine the distribution of pMBP and pMBP mRNA throughout the maternal-fetal junction in both early gestation tissues and at term. In early gestation tissues, pMBP was present only at the placental insertion site. Specifically, pMBP was present in (a) the decidua basalis (in the extracellular space, in interstitial pools and inside endometrial glands) and (b) intracellularly within extravillous interstitial trophoblasts in the decidua, in the myometrium and surrounding but not within luminal cells of spiral arteries. At term, the placental bed showed intense extracellular pMBP staining with little intracellular pMBP. In situ hybridization showed the presence of pMBP mRNA in both the early and late gestational tissues. pMBP mRNA was present in cells in the decidua, at the decidual-myometrial junction and in cell islands. Quantitative image analysis showed statistically significant hybridization signals with the pMBP antisense probe as compared to the control/sense probe. These results indicate that pMBP mRNA is expressed and pMBP is extensively deposited at the maternal-fetal junction in early pregnancy and at term.

Fibrous myopathy from butorphanol injections.

We describe an unusual, and probably underrecognized manifestation of intramuscular narcotic abuse. Fibrous myopathy is a deforming, fibrous infiltration of the muscles used for injection over a prolonged period. It is usually associated with pentazocine or meperidine injections, and to our knowledge, this is the first report of butorphanol causing the entity.