Is tibial tuberosity-trochlear groove distance an appropriate measure for the identification of knees with patellar instability?

PURPOSE: Tibial tuberosity-trochlear groove distance (TT-TG) has been regarded as a useful tool for establishing therapeutic choices for patellar instability. Recently, it has been shown that TT-TG negatively correlated with the quadriceps angle, suggesting that if used individually, neither provide a valid measure of instability. This study aimed to compare TT-TG distance between both knees in patients with unilateral instability to assess whether this measurement is a decisive element in the management decisions for patellar instability. METHODS: Sixty-two patients (18 male and 44 female), reporting to a specialist patella clinic for recurrent unilateral patellar instability, were included in the study. Patients underwent bilateral long leg computed tomography scan to determine TT-TG distance in both knees. Tibial TT-TG in symptomatic and asymptomatic knees in the same individual was compared statistically. RESULTS: Mean TT-TG distance in the symptomatic knee was 16.9 (±4.9) mm, compared to 15.6 (±5.6) mm in the asymptomatic knee. Tibial TT-TG was not significantly different between stable and unstable knees (n.s.). CONCLUSIONS: The lack of difference in TT-TG distance between stable and unstable knees suggests that TT-TG distance alone may not be a decisive element in establishing therapeutic choices for patellar instability. It should, therefore, be interpreted with caution during clinical evaluations. LEVEL OF EVIDENCE: II.

The relationship between quadriceps angle and tibial tuberosity-trochlear groove distance in patients with patellar instability.

PURPOSE: The quadriceps angle (Q-angle) represents the angle between the vector of action of the quadriceps and the patellar tendon. An increased Q-angle has been associated with an increased risk of patellar instability, although there is disagreement on its reliability and validity as it is affected by the position of the limb and contraction of the quadriceps. Tibial tuberosity-trochlear groove distance (TT-TG) is ascertained by axial CT scanning, with an increased value associated with patellar instability. This study aimed to determine whether the Q-angle correlates with the TT-TG distance in patients with patellar instability. METHODS: Q-angles were measured in 34 knees that had previously undergone CT scanning for assessment of patellar instability. Measurements were made with the patient supine, the knee extended and the lower limbs in neutral rotation with the quadriceps relaxed and contracted. TT-TG distance was measured on CT scanning in an identical position. RESULTS: Of the 34 knees measured, 24 had symptoms of patellar instability, and 10 were normal. A significant negative correlation between relaxed Q-angle and TT-TG in all knees was demonstrated (p = 0.028). In symptomatic knees, contracted Q-angle also demonstrated a significant negative correlation with TT-TG (p = 0.037). CONCLUSIONS: If TT-TG distance is regarded as the gold standard measurement, Q-angle is not a reliable indicator of patellar instability. There is a clear need to develop methods to more fully characterise the knee and factors contributing to patellar instability. LEVEL OF EVIDENCE: II.

Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses to SARS-CoV-2 in mild or moderate non-hospitalised patients.

BACKGROUND: Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease. METHODS: Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples. RESULTS: A sensitivity and specificity of 98.6% (95% CI, 92.6-100.0), 98.3% (95% CI, 96.4-99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%). CONCLUSIONS: The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.

Diagnostic accuracy of single-compartment magnetic resonance arthrography in detecting common causes of chronic wrist pain.

We reviewed a series of 50 consecutive wrist arthroscopy patients who had been investigated pre-operatively by direct magnetic resonance arthrography and calculated the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of magnetic resonance arthrography in detecting full-thickness triangular fibrocartilage complex tears, intrinsic carpal ligamentous lesions, wrist synovitis and chondral lesions in the radiocarpal joint. The sensitivities of magnetic resonance arthrography in detecting central triangular fibrocartilage complex tears, peripheral triangular fibrocartilage complex tears, scapholunate ligament tears, lunotriquetral ligament tears, dorsal synovitis and radiocarpal chondral lesions were 89%, 63%, 71%, 100%, 32% and 65%, respectively, and its specificities in detecting these lesions were 91%, 98%, 89%, 94% 94% and 97%, respectively. This study suggests that single compartment direct wrist magnetic resonance arthrography can provide high diagnostic accuracy for full-thickness triangular fibrocartilage lesions, intrinsic carpal ligament tears and chondral lesions in the radiocarpal joint, but that it is much less accurate in diagnosing synovitis of the radiocarpal joint. LEVEL OF EVIDENCE: III.

Differential induction of suppressor macrophages by cloned Lewis lung carcinoma variants in mice.

The splenic T-lymphocyte blastogenic and natural killer cell (NK) activities of C57BL/6 mice bearing cloned metastatic C3 or nonmetastatic C8 variants of the Lewis lung carcinoma were suppressed. The suppression was greater in mice bearing the metastatic C3 tumors than the nonmetastatic C8 tumors, although primary tumor sizes were similar. Macrophages were shown to cause this differential in immune responsiveness, while depletion of splenic macrophages by adherence restored the T-cell and NK responses. Also, splenic macrophages from C3 tumor bearers were more suppressive to normal spleen cell activities than were splenic macrophages from C8 tumor bearers. The suppression by the macrophages of C3 bearers was indomethacin sensitive and was associated with an increased secretion of prostaglandin E2 (PGE2). Normal macrophages incubated with C3 culture supernatants were more suppressive to NK and T-cell activities and secreted more PGE2 than did macrophages incubated with the C8 supernatants or with medium. This finding suggested that the immune suppression in mice bearing C3 tumors was initiated by a soluble tumor factor(s) that stimulated the development of prostaglandin-dependent suppressor macrophages. An in vivo study examined if treating C3-bearing mice with indomethacin to prevent the prostaglandin-dependent macrophage suppressor activity would influence host survival. The survival time of C3-bearing mice treated with indomethacin was prolonged. These results suggest that the macrophage-mediated immune suppression induced by tumor cells may facilitate tumor growth and metastasis.

Prostaglandin E2 production by EL 4 leukemia cells from C57BL/6 mice: mechanism for tumor dissemination.

Murine EL 4 leukemia cells contained and secreted prostaglandin E2 (PGE2). PGE2 was secreted into the culture media during in vitro growth, as well as into plasma during growth in the peritoneum of inbred C57BL/6 mice. For the study of the role of PGE2 in tumor dissemination, migration of EL 4 cells out of glass capillary tubes was used as an in vitro model for tumor spread in a host. PGE2 enhanced the in vitro migration of EL 4 cells while indomethacin, a prostaglandin synthesis inhibitor, reduced the extent of migration. When EL 4 cells were allowed to migrate into medium containing both indomethacin and PGE2, the cells exhibited an enhanced migration ability suggesting an extrinsic effect on cells by PGE2. The participation of tumor-derived PGE2 in promoting tumor spread in a host was supported by demonstration that EL 4 cells grown in indomethacin-treated mice secreted less PGE2 and had reduced in vivo dissemination ability. These results indicated that tumor spread was promoted by tumor-derived PGE2. The extent of migration and dissemination can be reduced by prostaglandin synthesis inhibitors such as indomethacin.

Macrophage-mediated suppression of natural killer cell activity in mice bearing Lewis lung carcinoma.

The natural killer (NK) cell cytotoxic capacity of C57BL/6 mice with implantation of Lewis lung carcinoma (LLC) was quantitated during tumor growth. The NK activity became suppressed at 1 week of tumor growth and remained suppressed. The mechanisms for the suppression during the first 3 weeks of tumor growth included secretion of prostaglandin E2 (PGE2) by both the LLC tumor and host macrophages. With tumor growth, plasma PGE2 concentrations progressively increased. Oral administration of indomethacin to tumor-bearing mice prevented the rise in serum PGE2 concentrations and the suppression of NK activity. Cultured LLC cells and splenic macrophages isolated from mice during the first 3 weeks of tumor growth secreted increased amounts of PGE2. Macrophages from tumor-bearer spleen cells were shown to suppress NK activity. Depletion of these macrophages restored the NK activity, and addition of these macrophages to normal spleen cells resulted in an indomethacin-sensitive suppression of the NK response. The mechanisms of suppression in mice bearing large tumors were different than those observed with smaller tumors. With a large tumor burden, the plasma PGE2 concentrations declined. Indomethacin treatment did not prevent the suppression of NK activity, and depletion of splenic macrophages did not restore NK cytotoxicity.

Enhancement of Lewis lung carcinoma cell migration by prostaglandin E2 produced by macrophages.

The role of macrophages in tumor metastasis was examined by using migration of a cloned metastatic Lewis lung carcinoma (LLC) variant, LLC-C4, out of glass capillary tubes as an in vitro model for dissemination of tumor cells from a primary tumor mass. Macrophages, derived from LLC tumors of C57BL/6 mice or from peritoneal exudates of mice given injections of complete Freund's adjuvant, enhanced tumor cell migration through an indomethacin-sensitive mechanism. Resident peritoneal macrophages did not produce a tumor migration-enhancing activity but could be induced to do so by preincubation with LLC-C4 cells or their culture supernatants. The capacity of macrophages to enhance LLC-C4 migration corresponded to their secretion of prostaglandin E2. Addition of similar concentrations of prostaglandin E2 to the migration medium of LLC-C4 cells enhanced their migration out of the capillary tubes. These results suggest that macrophages, following exposure to tumor cells or their products or following stimulation with complete Freund's adjuvant, secrete elevated amounts of prostaglandin E2 which in turn may enhance tumor dissemination.

Relationships between morphology, dissemination, migration, and prostaglandin E2 secretion by cloned variants of Lewis lung carcinoma.

Lewis lung carcinoma cells (LLC) were isolated and cloned from metastatic lung nodules of C57BL/6 mice or from a cultured parental LLC line. Their dissemination abilities were defined in vivo by their capacities to disseminate to the lungs following s.c. or i.v. injection into mice and in an in vitro model for tumor dissemination by their ability to migrate out of glass capillary tubes. Cloned LLC cells with an enhanced dissemination capacity exhibited a rounded morphology, were nonadherent during in vitro culture, and readily migrated out of capillary tubes. In contrast, clones not capable of dissemination were adherent and spread during in vitro culture and did not migrate out of capillary tubes. Production of prostaglandin E2 by these clones was measured by a radioimmunoassay. An inverse relationship was observed between the extent of migration and dissemination of clones and their ability to secrete prostaglandin E2 in vitro and in vivo. However, the prostaglandin E2 did not regulate the migration-dissemination capacities of LLC clones as inhibiting prostaglandin synthesis did not alter their capacity to migrate in vitro or to lodge in the lungs following i.v. inoculation into mice.

Hematopoiesis and suppressor bone marrow cells in mice bearing large metastatic Lewis lung carcinoma tumors.

Mice bearing a metastatic variant of Lewis lung carcinoma (LLC-C3) were studied to determine if there might be a relationship between tumor induced hematopoiesis and immune suppression. Growth of LLC-C3 in C57BL/6 mice corresponded with increased hematopoiesis and an increase in the proportion of monocytes in the peripheral blood, spleen, and bone marrow. The LLC-C3 cells secreted colony stimulating factor activity and, thus, could have directly stimulated the hematopoiesis in the hosts. As tumor growth progressed, the bone marrow of the tumor bearing mice became suppressive to T-cell blastogenesis. The bone marrow suppressor cells obtained from mice bearing large (greater than 3 g) LLC-C3 tumors were nonadherent to nylon wool, sensitive to treatment with L-leucine methyl ester, insensitive to treatment with anti-Thy-1.2 and complement, and mediated their suppression through an indomethacin sensitive mechanism. Secretion of colony stimulating factor activity by the LLC-C3 cells could have induced the appearance of the bone marrow suppressor cells since normal bone marrow cells which were cultured in the presence of LLC-C3 culture supernatants had an increased proportion of monocytes and were suppressive to T-lymphocyte blastogenesis. Our results suggest that the colony stimulating factor activity produced by LLC-C3 cells stimulates hematopoiesis which, in turn, could result in the appearance of bone marrow suppressor cells.

Body composition of adult cystic fibrosis patients and control subjects as determined by densitometry, bioelectrical impedance, total-body electrical conductivity, skinfold measurements, and deuterium oxide dilution.

This study contrasts body compositions (by six methods) of eight cystic fibrosis (CF) subjects with those of eight control subjects matched for age, height, and sex. CF subjects weighed 84% as much as control subjects. Densitometry and two bioelectrical impedance-analysis methods suggested that reduced CF weights were due to less lean tissue (10.7, 9.5, and 10.4 kg). Total-body electrical conductivity (TOBEC) and skinfold-thickness measurements indicated that CF subjects were leaner than control subjects and had less fat (5.4 and 3.6 kg) and less lean (5.2 and 7 kg) tissue. D2O dilution showed a pattern similar to TOBEC (8.3 kg less lean, 2.7 kg less fat tissue). Densitometry estimates of fat (mass and percent) were not correlated (r less than 0.74, p greater than 0.05) with any other method for CF subjects but were correlated with all other methods for control subjects. CF subjects contained less fat and lean tissue than did control subjects. Densitometry by underwater weighing is unsuitable for assessing body composition of CF patients.

A conserved pseudouridine modification in eukaryotic U2 snRNA induces a change in branch-site architecture.

The removal of noncoding sequences (introns) from eukaryotic precursor mRNA is catalyzed by the spliceosome, a dynamic assembly involving specific and sequential RNA-RNA and RNA-protein interactions. An essential RNA-RNA pairing between the U2 small nuclear (sn)RNA and a complementary consensus sequence of the intron, called the branch site, results in positioning of the 2'OH of an unpaired intron adenosine residue to initiate nucleophilic attack in the first step of splicing. To understand the structural features that facilitate recognition and chemical activity of the branch site, duplexes representing the paired U2 snRNA and intron sequences from Saccharomyces cerevisiae were examined by solution NMR spectroscopy. Oligomers were synthesized with pseudouridine (psi) at a conserved site on the U2 snRNA strand (opposite an A-A dinucleotide on the intron strand, one of which forms the branch site) and with uridine, the unmodified analog. Data from NMR spectra of nonexchangeable protons demonstrated A-form helical backbone geometry and continuous base stacking throughout the unmodified molecule. Incorporation of psi at the conserved position, however, was accompanied by marked deviation from helical parameters and an extrahelical orientation for the unpaired adenosine. Incorporation of psi also stabilized the branch-site interaction, contributing -0.7 kcal/mol to duplex deltaG degrees 37. These findings suggest that the presence of this conserved U2 snRNA pseudouridine induces a change in the structure and stability of the branch-site sequence, and imply that the extrahelical orientation of the branch-site adenosine may facilitate recognition of this base during splicing.

Adhesiveness and morphology of Lewis lung carcinoma variants influence their sensitivity to natural killer cytolysis and their metastatic capacity.

Cloned metastatic Lewis lung carcinoma cells, C3, were more resistant to natural killer (NK) lysis than were nonmetastatic variant cells, C8. This was influenced by the tumor cell adhesiveness and morphology. When the nonadherent round C3 cells were cultured with dimethylsulfoxide, they became adherent and spread, sensitive to NK lysis and less metastatic. When the adherent and spread C8 cells were made nonadherent and round with cytochalasin B, they became more resistant to NK lysis and more metastatic. These metastatic differences were not observed in 3-week-old NK-deficient mice.

Transition to adulthood of female garment-factory workers in Bangladesh.

This article examines data from a study on garment-factory workers in Bangladesh to explore the implications of work for the early socialization of young women. For the first time, large numbers of young Bangladeshi women are being given an alternative to lives in which they move directly from childhood to adulthood through early marriage and childbearing. Employment creates a period of transition in contrast to the abrupt assumption of adult roles at very young ages that marriage and childbearing mandate. This longer transition creates a period of adolescence for young women working in the garment sector that is shown to have strong implications for the women's long-term reproductive health.

PIP: In contrast to the abrupt assumption of adult roles at very young ages associated with early marriage and childbearing, employment offers women in developing countries a period of transition between childhood and adulthood. The implications of labor force participation for the early socialization of young women were examined in semi-structured interviews with 22 garment factory workers in Dhaka, Bangladesh. 47% of these women entered the garment industry before 15 years of age and 97% had migrated from rural areas. Entry into work was easier in cases where a support structure existed to facilitate migration, help with the job search, and provide some level of initial subsistence. Most women who had worked in the garment industry for more than a year had changed factories at least once and been promoted from helper to operator, with attendant income increases. Female garment workers face social stigmatization for their violation of seclusion rules, are incorrectly assumed to be sexually active, and suffer from numerous stress-related physical symptoms. Nonetheless, these young women valued the modern nature of their life-style and chance to be part of a peer network, considered garment work preferable to agricultural labor, appreciated the opportunity to help their families financially and learn money management skills, and became more self-assured and independent. Factory work in the garment industry may be regarded as a positive opportunity for young girls to delay marriage and motherhood and reduce their reliance on more risky forms of employment.

A cost comparison of allogeneic and preoperatively or intraoperatively donated autologous blood.

We determined the cost of allogeneic packed red blood cells and autologous whole blood donated either preoperatively or in the operating room during hemodilution. Direct and indirect cost estimates were based on patients requiring simple transfusion and included procurement and preparation of the blood including testing performed, materials and time used, waste, and materials for administration. Data were derived from prospective blood bank time studies, material invoice records, and retrospective review of anesthesia times. Viral infection and transfusion reaction costs were accepted from previously published sources. Direct cost of purchasing and indirect costs of preparation resulted in an overall cost of $107.26 for the first unit of allogeneic packed red blood cells transfused. A second unit was slightly less costly ($100.89), as no type and screen was required and the same delivery set and filter can be used. The total cost of acquisition, processing, and transfusion of 1 U of preoperatively donated autologous blood was $97.83. The total cost of a 2-U transfusion of autologous whole blood donated in the operating room during acute normovolemic hemodilution was $83.10. These data suggest that autologous predonation of whole blood is somewhat less expensive than allogeneic packed red blood cells, and that hemodilution may be a cost effective alternative to autologous predonation in selected patients.