Clinical outcomes following surgical management of insertional Achilles tendinopathy using a double-row suture bridge technique with mean two-year follow-up.

BACKGROUND: The clinical outcomes following surgical management of insertional Achilles tendinopathy (IAT) vary depending on the surgical technique used to reattach the Achilles tendon following debridement. The aim of this study was to investigate the clinical outcomes of patients with IAT who underwent surgical management with a double-row suture bridge technique used to reattach the Achilles tendon. METHODS: A retrospective review of consecutive patients diagnosed with IAT, who underwent surgical management utilising a double-row suture bridge technique (Arthex Speedbridge), and a minimum of 3-month follow-up were included. The primary outcome was the Manchester-Oxford Foot Questionnaire (MOXFQ) Index score which is a patient reported outcome measure (PROM). Secondary outcomes included EuroQol EQ-5D-5L health-related quality of life PROM and complication rates. RESULTS: Between July 2013 and June 2020, 50 consecutive patients (23 male; 27 female) were included. The mean age (± standard deviation) was 52.3 ± 11.3 (range 29.0-84.3). Pre- and post-operative PROM data were available for all cases. The mean follow-up was 2.4 ± 1.9 years. The MOXFQ Index score improved from 48.5 to 12.4 (p < 0.01), EQ-5D-5L improved from 2.7 ± 0.46 to 1.2 ± 0.37 (p < 0.01), and EQ-VAS improved from 48.0 ± 18.4 to 84.1 ± 12.6 (p < 0.01). Four patients had complications which were of minimal clinical relevance and caused no deviation from routine recovery. There were no cases of tendon rupture. CONCLUSION: This study has demonstrated that surgical management of IAT is safe and effective with clinical improvement in both clinical and general health-related quality of life outcome PROMs. LEVEL OF EVIDENCE: IV.

Health-related quality of life in patients with Achilles tendinopathy: Comparison to the general population of the United Kingdom.

BACKGROUND: There is little evidence available regarding the impact of Achilles Tendinopathy (AT) on health-related quality of life (HRQOL). The primary aim of this study was to quantify the clinical and health-related quality-of-life patient-reported outcome measures for a population presenting with either mid-substance or insertional Achilles tendinopathy. METHODS: A prospective comparative observational study of consecutive patients with AT presenting for extracorporeal shockwave therapy (ESWT) at a large teaching hospital. The primary outcome was assessment of a validated health-related quality of life PROMs (Euroqol EQ-5D-5L) and comparison to 2 general UK population datasets. The secondary outcomes were Visual Analogue Pain Scale (VAS-Pain) and two validated foot-specific patient reported outcome measures (Foot Function Index (FFI) and Victorian Institute of Sports Assessment-Achilles (VISA-A)). RESULTS: Between March 2014 and June 2021, 320 consecutive patients (125 male; 195 female) were diagnosed with AT and referred for a first course of ESWT. EQ-5D-5L PROMs were prospectively collected for 303 of these patients (94.7%). The mean age (± standard deviation(SD)) was 52.1 ± 11.4 years. The mean EQ-5D-5L Index score (mean±SD) for the AT cohort was 0.783 ± 0.131. Patients less than 55 years with AT had a statistically significantly worse quality of life compared with members of the same age group in the general population. The mean VAS-Pain, FFI, VISA-A clinical outcome scores were 6.0 ± 2.3, 49.5 ± 21.2 and 34.1 ± 14.4 respectively. There was a statistically significant moderate correlation between HRQOL and clinical PROMs (VAS-Pain and FFI vs EQ-5D) however there was no correlation with age. CONCLUSION: This study demonstrates that patients under the age of 55 with AT have a significantly reduced quality of life compared with the general population. LEVEL OF EVIDENCE: III.

Parathyroid allotransplantation to treat post-thyroidectomy hypoparathyroidism: A review of case studies.

OBJECTIVE: Symptomatic long-term hypoparathyroidism following thyroid surgery requires an alternative and permanent therapy that would effectively restore parathyroid function and eliminate the need for substitution drug therapy. The aim of this study was to systematically review the literature on the efficacy and safety of parathyroid allotransplantation to treat post-operative hypoparathyroidism. METHODS: MEDLINE, Embase, BIOSIS and the Cochrane Library were searched for published articles (from inception of each database to September 30, 2018). A total of 9 studies comprising 146 patients (177 allotransplantations) with post thyroidectomy hypoparathyroidism were identified. RESULTS: Parathyroid tissues used for allotransplant were cultured parathyroid cells, cryopreserved parathyroid cells and encapsulated microspheres. Post-transplant immunosuppression was only reported in three studies, mainly with oral prednisolone for 2 weeks to 6 months. Mean graft survival following allotransplantation was 47% (95% CI 24%-71%) when patients were followed-up to 6 months and 41% (95% CI 2.3%-80%) at 12 months. There was significant unexplained heterogeneity observed between studies in both these groups (I2 > 50%). Parathyroid hormone (PTH) levels, and serum calcium levels post intervention was not reported in all studies, but available evidence suggests the levels remains higher (PTH level around 12 pg/ml; Ca level around 8 mg/dl) post-allotransplantation for up to 24 months. CONCLUSIONS: Long-term benefit and harms of allotransplantation is still unclear due to the clinical and statistical heterogeneity observed among the studies. Therefore, conduct of a well-designed controlled clinical trial in the immediate future on allotransplantation is of paramount importance.

Partnered pharmacist charting on admission in the General Medical and Emergency Short-stay Unit - a cluster-randomised controlled trial in patients with complex medication regimens.

WHAT IS KNOWN AND OBJECTIVE: Patients admitted to general medical units and emergency short-stay units are often complex with multiple comorbidities, polypharmacy and at risk for drug-related problems associated with increased morbidity and mortality. The aim of this study was to evaluate the effectiveness of a partnered pharmacist charting model completed at the time of admission to prevent medication errors. METHODS: We conducted an unblinded cluster randomized controlled trial comparing partnered pharmacist charting to standard medical charting among patients admitted to general medical units and emergency short-stay units with complex medication regimens or polypharmacy. This trial was conducted at an adult major referral hospital in metropolitan Melbourne, Australia, with an annual emergency department attendance of approximately 60 000 patients. The evaluation included patients' medication charts written in the period of 16 March 2015 to 27 July 2015. Patients randomized to the intervention were managed using the partnered pharmacist charting model. The primary outcome variable was a medication error identified by an independent assessor within 24 h of admission, who was not part of the patient's admission process. RESULTS: Of the 473 patients who received standard medical staff charting during the study period, 372 (78·7%) had at least one medication error identified compared to 15 patients (3·7%) on the partnered pharmacist charting arm (P < 0·001). The relative risk of an error with standard medical charting was 21·4 (95% CI: 13·0-35·0) with a number needed to treat (NNT) to prevent one error of 1·3 (95% CI: 1·3-1·4), and the relative risk of a high or extreme risk error with standard medical charting was 150·9 (95% CI: 21·2-1072·9) with a NNT to prevent one high or extreme error of 2·7 (95% CI 2·4-3·1). WHAT IS NEW AND CONCLUSION: Partnering between medical staff and pharmacists to jointly chart initial medications on admission significantly reduced inpatient medication errors (including errors of high and extreme risk) among general medical and emergency short-stay patients with complex medication regimens or polypharmacy.

SLICC/ACR damage index independently associated with left ventricular diastolic dysfunction in patients with systemic lupus erythematosus.

Left ventricular (LV) diastolic dysfunction has been reported in both active and inactive systemic lupus erythematosus (SLE) patients without clinical evidence of cardiovascular disease. However, the relationship between the long-term inflammatory burden reflected by the SLICC/ACR damage index and LV diastolic function has not been studied. Eighty-two SLE patients and 82 controls matched for age, sex, body mass index, blood pressure and heart rate underwent echocardiography with tissue Doppler imaging (TDI). LV diastolic function was estimated by the myocardial early diastolic velocity (E') at the lateral annulus. There were 51 patients (62.2%) with nephritis, 23 patients (28.0%) with hypertension, 21 patients (25.6%) with vasculitis, 16 patients (19.5%) with pulmonary hypertension, 4 patients (4.9%) with cerebrovascular disease and 2 patients (2.4%) with diabetes mellitus. Sixty-two patients (75.6%) were taking prednisone and 35 patients (42.7%) used a immunosuppressant. Forty-five patients (54.8%) had active disease and suffered from disease-related end-organ damage. Patients with SLICC/ACR damage index ≥1 had more evidence of LV diastolic dysfunction with lower lateral annulus E' (9.6 ± 3.4 vs 12.9 ± 3.5 cm/s, p < 0.001) than those without. In addition, the proportion of patients with abnormal LV myocardial relaxation (defined as lateral E' < 10.0 cm/s) (51.1% vs 16.2%, χ(2) = 10.8, p = 0.001) were significantly higher. Multivariate analysis showed that the SLICC/ACR damage index ≥1 was independently associated with LV diastolic dysfunction (OR = 3.80, 95%CI: 1.21-11.95, p = 0.023) after adjusting for hypertension, disease duration and medical therapy. This may suggest that the overall inflammatory burden in SLE, as reflected by SLICC/ACR damage index, is associated with the development of diastolic dysfunction in SLE patients.

Effects of rosuvastatin on subclinical atherosclerosis and arterial stiffness in rheumatoid arthritis: a randomized controlled pilot trial.

OBJECTIVE: To ascertain the effect of rosuvastatin on carotid atherosclerosis and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients were randomized in a double-blind placebo-controlled trial to receive 10 mg rosuvastatin (n = 24) or placebo (n = 26). Patients were followed prospectively every 3 months for 12 months. Intima-media thickness (IMT), augmentation index (AIx), and subendocardial viability ratio (SEVR) were measured at baseline, 6 and 12 months. RESULTS: Rosuvastatin resulted in statistically significant reductions of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and urate levels vs. placebo. However, rosuvastatin had no significant effect on changes in inflammatory markers, including C-reactive protein (CRP) levels [from 2.9 (1.4-11.0) to 3.1 (0.9-13.3) mg/L in the rosuvastatin group compared with from 5.8 (2.6-14.2) to 4.4 (1.2-12.3) mg/L in the placebo group]. Nonetheless, a significant improvement in the Disease Activity Score (DAS) and a reduction in fibrinogen level was observed at 6 and 12 months compared with baseline in the rosuvastatin group. The treatment group exhibited a significant increase in SEVR (from 157 ± 28% to 163 ± 33% in the rosuvastatin group compared with from 143 ± 18% to 143 ± 26% in the placebo group, p = 0.023), but no significant effect was observed in the changes in IMT and AIx. CONCLUSION: Our data suggest that rosuvastatin has a modest anti-inflammatory effect in RA patients with low disease activity in terms of reduction in DAS and fibrinogen level. Rosuvastastin may also improve subendocardial perfusion and lower the urate level.

Carbimazole-induced agranulocytosis: does antineutrophil cytoplasmic antibody have a role?

Carbimazole is a drug that is widely used for hyperthyroid disorders, such as Graves' disease. Agranulocytosis is a rare idiosyncratic adverse reaction to the drug which is potentially fatal. This report describes a patient with a history of successfully treated pyoderma gangrenosum, who developed agranulocytosis 3 weeks after commencement of carbimazole for Graves' disease. It may give credence to the theory that implicates antineutrophil cytoplasmic antibodies in the pathogenesis of agranulocytosis induced by antithyroid drugs.

Expression of syndecan-2 in the amoeboid microglial cells and its involvement in inflammation in the hypoxic developing brain.

The present study examined the expression of heparan sulphate proteoglycan, syndecan-2 (Sdc-2) in the corpus callosum and the amoeboid microglial cells (AMC) in the neonatal rat brain in response to hypoxia. In 1-day old Wistar rats subjected to hypoxia the mRNA and protein expression of Sdc-2 in the corpus callosum, heavily populated by AMC, was increased up to 3 days after the hypoxic exposure. Immunoexpression of Sdc-2 was localized in AMC as confirmed by double labeling using microglial marker. Primary cultures of microglial cells subjected to hypoxia showed a significant increase in Sdc-2 expression. Application of Sdc-2 to microglial cultures under hypoxia increased the release of tumor necrosis factor-alpha, interleukin-1beta, chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-X-C motif) ligand 12 (CXCL12) by the microglial cells. Additionally, Sdc-2 enhanced the production of reactive oxygen species (ROS) by microglia subjected to hypoxia. Edaravone [3-methyl-1phenyl-2-pyrazolin-5-one], an antioxidant drug, suppressed the hypoxia- and Sdc-2-induced increased production of cytokines, chemokines, and ROS. In the light of these findings, we suggest that Sdc-2 plays an important role in microglial production of inflammatory cytokines, chemokines, and ROS in hypoxic conditions. In this connection, edaravone suppressed the hypoxia- and Sdc-2-induced increased cytokine and ROS production suggesting its therapeutic potential in ameliorating neuroinflammation.

Effect of household passive smoking exposure on the risk of ischaemic heart disease in never-smoke female patients in Hong Kong.

OBJECTIVE: To investigate the relation between household passive smoking exposure and risk of ischaemic heart disease (IHD) among never-smoke female patients by a retrospective case-control analysis. METHODS: This study recruited 314 patients with IHD who had never smoked and 319 controls who were admitted for other reasons in the same hospital during the same period. Subjects were interviewed about their exposure to household passive smoking. The dose metrics of passive smoking exposure were evaluated by using "pack years" and "hour years", which indicated the cumulative amount and duration of exposure. The ORs and 95% CIs were computed by unconditional logistic regression, adjusted for other risk factors. RESULTS: Subjects with passive smoking exposure were associated with higher risk of IHD (OR 1.51, 95% CI 1.01 to 2.27, p = 0.043) when compared to non-exposed subjects. Subjects exposed to an average of > or =1 pack of cigarette per day had an OR of 1.69 (95% CI 1.07 to 2.68, p = 0.025). The OR was 1.52 for those exposed for > or =5 years (95% CI 1.01 to 2.29, p = 0.043) and was 1.82 for those exposed > or =4 h per day (95% CI 1.05 to 3.15, p = 0.032). Similarly, the risk of IHD increased with cumulative exposure duration, with an OR of 1.53 (95% CI 1.01 to 2.32, p = 0.043) at the exposure level > or =5 pack years, and an OR of 1.61 (95% CI 1.03 to 2.52, p = 0.037) at the exposure level > or =20 hour years. There was a significant dose-response association between the exposure measures and risk of IHD (p<0.01 for trend). CONCLUSION: Our data suggested an increased risk of IHD from passive household smoking in female never-smoke subjects, and demonstrated a dose-response association.

Kinesin superfamily: roles in breast cancer, patient prognosis and therapeutics.

Breast cancer pathobiology is known to be influenced by the differential expression of a group of proteins called the kinesin superfamily (KIFs), which is instrumental in the intracellular transport of chromosomes along microtubules during mitosis. During cellular division, kinesins are strictly regulated through temporal synthesis so that they are present only when needed. However, their misregulation may contribute to uncontrolled cell growth owing to premature sister chromatid separation, highlighting their importance in cancer. This review covers the functions of kinesins in normal and breast cancer cells, the use of kinesins for breast cancer patient prognosis, and the targeting of these molecules for therapeutics. A better understanding of KIF proteins may be pivotal to improved disease outcomes for breast cancer patients.

Mechanisms, patterns and outcomes of paediatric polytrauma in a UK major trauma centre.

Introduction Paediatric trauma is a significant burden to healthcare worldwide and accounts for a large proportion of deaths in the UK. Methods This retrospective study examined the epidemiological data from a major trauma centre in the UK between January 2012 and December 2014, reviewing all cases of moderate to severe trauma in children. Patients were included if aged ≤16 years and if they had an abbreviated injury scale score of ≥2 in one or more body region. Results A total of 213 patients were included in the study, with a mean age of 7.8 years (standard deviation [SD]: 5.2 years). The most common cause of injury was vehicle related incidents (46%). The median length of hospital stay was 5 days (interquartile range [IQR]: 4-10 days). Approximately half (52%) of the patients had to stay in the intensive care unit, for a median of 1 day (IQR: 0-2 days). The mortality rate was 6.6%. The mean injury severity score was 19 (SD: 10). Pearson's correlation coefficient showed a positive correlation for injury severity score with length of stay in hospital (p<0.001). Conclusions There is significant variation in mechanism of injury, severity and pattern of paediatric trauma across age groups. A multidisciplinary team approach is imperative, and patients should be managed in specialist centres to optimise their care and eventual functional recovery. Head injury remained the most common, with significant mortality in all age groups. Rib fractures and pelvic fractures should be considered a marker for the severity of injury, and should alert doctors to look for other associated injuries.

Microfluidic Imaging Flow Cytometry by Asymmetric-detection Time-stretch Optical Microscopy (ATOM).

Scaling the number of measurable parameters, which allows for multidimensional data analysis and thus higher-confidence statistical results, has been the main trend in the advanced development of flow cytometry. Notably, adding high-resolution imaging capabilities allows for the complex morphological analysis of cellular/sub-cellular structures. This is not possible with standard flow cytometers. However, it is valuable for advancing our knowledge of cellular functions and can benefit life science research, clinical diagnostics, and environmental monitoring. Incorporating imaging capabilities into flow cytometry compromises the assay throughput, primarily due to the limitations on speed and sensitivity in the camera technologies. To overcome this speed or throughput challenge facing imaging flow cytometry while preserving the image quality, asymmetric-detection time-stretch optical microscopy (ATOM) has been demonstrated to enable high-contrast, single-cell imaging with sub-cellular resolution, at an imaging throughput as high as 100,000 cells/s. Based on the imaging concept of conventional time-stretch imaging, which relies on all-optical image encoding and retrieval through the use of ultrafast broadband laser pulses, ATOM further advances imaging performance by enhancing the image contrast of unlabeled/unstained cells. This is achieved by accessing the phase-gradient information of the cells, which is spectrally encoded into single-shot broadband pulses. Hence, ATOM is particularly advantageous in high-throughput measurements of single-cell morphology and texture - information indicative of cell types, states, and even functions. Ultimately, this could become a powerful imaging flow cytometry platform for the biophysical phenotyping of cells, complementing the current state-of-the-art biochemical-marker-based cellular assay. This work describes a protocol to establish the key modules of an ATOM system (from optical frontend to data processing and visualization backend), as well as the workflow of imaging flow cytometry based on ATOM, using human cells and micro-algae as the examples.

Nuclear morphometry in columnar cell lesions of the breast: is it useful?

AIMS: To evaluate the nuclear morphometric features of breast columnar cell lesions (CCLs) observed on mammotome core biopsies, to determine if there are significant measurable differences between those with atypia and those without. Correlation with follow-up open excision specimens was made. METHODS: Mammotome core biopsies performed on patients that contained CCLs were derived from the departmental case files. Histological material was reviewed and foci of CCLs demarcated for nuclear morphometric assessment, which was accomplished using an imaging system. Nuclear parameters studied were nuclear area and perimeter, circularity factor and feret's diameter. Statistical analysis used the GraphPad Prism software, with p<0.05 indicating significance. RESULTS: On examination of core biopsies of 40 patients with CCLs, 8 lesions were benign, 4 showed atypical lobular hyperplasia, 8 showed CCLs with nuclear atypia, 19 disclosed atypical ductal hyperplasia (ADH) and 1 showed ductal carcinoma in situ (DCIS). The nuclear area, perimeter and feret's diameter of CCLs with atypia were significantly greater than those without (p = 0.04, 0.03 and 0.019, respectively), whereas no difference was observed in the circularity factor. Follow-up open excision biopsy specimens in 24 patients showed upgrading to DCIS in 40% of cases diagnosed initially with ADH on core biopsy compared with 20% of CCLs with atypia. CONCLUSIONS: Nuclear morphometry in CCLs confirms nuclear size as the key parameter in the assessment of nuclear atypia. Whether it can be potentially used as an adjunctive tool depends on the establishment of appropriate cut-offs.

Up-regulation of metallothionein isoforms in keloid keratinocytes.

Keloids are proliferative growths of dermal collagen, usually resulting from excessive tissue response during wound healing. There is evidence that keratinocytes may promote keloidogenesis via epithelial-mesenchymal interactions. Metallothioneins (MTs) are known to be involved in the fundamental cellular processes of growth and apoptosis. In this study, we evaluated the expression of MT isoforms in normal and keloid keratinocytes. The expression patterns of ten functional MT isoforms were assessed using real-time RT-PCR in primary cultures of normal and keloid keratinocytes. The MT-2A isoform was the most abundant MT isoform in both normal and keloid keratinocytes while the MT-1B isoform was absent. There was a significant increase in the mRNA expression of four MT isoforms, viz. MT-1A, 1E, 1F and 2A in keloid keratinocytes as compared to normal keratinocytes. Up-regulation of MT-1A, 1E, 1F and 2A isoforms may play a part in the development of keloids by paracrine signaling.

Cardiovascular complications of severe acute respiratory syndrome.

BACKGROUND AND AIMS: Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular complications. METHODS AND RESULTS: 121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hospital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (chi(2) = 3.99, p = 0.046) and third week (chi(2) = 6.53, p = 0.01), although it could not explain tachycardia during follow up. CONCLUSIONS: In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.

Beta-blockade in heart failure: a comparison of carvedilol with metoprolol.

OBJECTIVES: This study was performed to compare the long-term clinical efficacy of treatment with metoprolol versus carvedilol in patients with chronic heart failure. BACKGROUND: Beta-adrenergic blockade is of proven value in chronic heart failure. Metoprolol, a selective beta-blocker, is widely used, but recent trials suggest carvedilol, a nonselective beta-blocker with alpha-1-receptor antagonist activity and antioxidant activities, is also effective. It is uncertain, however, if these additional properties of carvedilol provide further clinical benefit compared with metoprolol. METHODS: In this randomized double-blind control trial, 51 patients with chronic heart failure and mean left ventricular (LV) ejection fraction of 26% +/- 1.8% were randomly assigned treatment with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy after a four-week dose titration period for a total of 12 weeks. Response was assessed by a quality of life questionnaire, New York Heart Association class, exercise capacity (6-min walk test), radionucleotide ventriculography for LV ejection fraction, two-dimensional echocardiography measurement of LV dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate variability. RESULTS: Both carvedilol and metoprolol produced highly significant improvement in symptoms (p < 0.001), exercise capacity (p < 0.05) and LV ejection fraction (p < 0.001), and there were no significant differences between the two drugs. Carvedilol had a significantly greater effect on sitting and standing blood pressure, LV end-diastolic dimension and normalized the mitral E wave deceleration time. CONCLUSIONS: Both metoprolol and carvedilol were equally effective in improving symptoms, quality of life, exercise capacity and LV ejection fraction, although carvedilol lowers blood pressure more than metoprolol.

Natural killer cell subsets in long-term renal allograft recipients. A phenotypic and functional study.

Natural Killer cell subsets were studied in 39 long-term renal allotransplant recipients receiving conventional immunosuppression and 26 normal controls. Two-color flow cytometry analysis was used to determine coexpression of 2 surface antigens known to allow a phenotypic and functional discrimination of NK cells--Leu-7 a marker of large granular lymphocytes, and Leu-11c directed against the FcgammaR. In 11 patients and controls, these NK cell subsets were compared with actual NK activity assessed by killing of K562 target cells. Our data clearly show that, in long-term kidney recipients, the absolute number of NK cells (Leu-11c+) is significantly decreased compared with that of the control group. Furthermore, the most cytotoxic NK cell subset (Leu-7-/Leu-11c+ phenotype) is markedly diminished in the transplant population, whereas the less cytotoxic subset (Leu-7+/Leu-11c+) is unchanged. Finally, actual NK cell activity closely correlates with both relative and absolute numbers of these 2 NK cell subsets. These data provide convincing evidence that NK activity is impaired in long-term kidney recipients because of a diminished number of NK effector cells.

Characterization of an expanded large granular lymphocyte subset lacking natural killer activity present in renal allograft recipients.

We have previously reported that, in long-term renal allograft recipients who receive chronic chemical immunosuppression and who are at risk for late chronic viral infections and virus associated tumors, the percentage of lymphocytes the phenotype of which is Leu-7+/Leu-11(-) (CD16) is markedly and significantly increased compared with that in normal controls. Since this population may lack natural killer (NK) activity and may explain the state of decreased host resistance, we carried out studies in 16 kidney transplant recipients on conventional immunosuppression and 10 age-matched normal controls to further define the phenotype, the morphology, and the NK cell activity of this particular subset. Using two-color flow cytometry analysis we found that the Leu-7+ cell subset comprises two essentially nonoverlapping subpopulations, depending on whether cells are coexpressing the NK cell marker Leu-11/CD16 (Leu-7+/Leu-11+ phenotype) or the pan-T cell marker Leu-4/CD3 (Leu-7+/Leu-4+ phenotype). We thus demonstrated that Leu-7+/Leu-11- cells do coexpress the Leu-4+/CD3 surface determinant. The percentage of Leu-7+/Leu-4+ (CD3) is significantly elevated in transplant recipients compared with that in normal controls (26 +/- 4% versus 8 +/- 2%, P less than 0.005). In contrast, the size of the Leu-7+/Leu-11+ cell subset is similar in both groups. Although in transplant recipients 70% of Leu-7+ cells coexpress Leu-4/CD3, only 43% do so in the control group. Cell sorter experiments isolated the Leu-7+/Leu-4+ cells and showed that morphologically these cells are typical large granular lymphocytes that cannot be distinguished from Leu-11+ NK cells. NK-sensitive K562 target cells showed no cytotoxicity. In contrast, Leu-7+/Leu-11+ cells exhibited high killing activity. Therefore, in long-term stable renal allograft recipients at increased risk of developing cancers and chronic viral infections, a subpopulation of non-NK large granular lymphocytes, the phenotype of which is Leu-7+/Leu-11-/Leu-4+, is abnormally expanded. This subset likely contributes to the diminished functional attributes of the chronic drug-induced immunodeficiency.

Comparison of frequencies of left ventricular systolic and diastolic heart failure in Chinese living in Hong Kong.

There is a wide variation (13% to 74%) in the reported prevalence of heart failure associated with normal left ventricular (LV) systolic function (diastolic heart failure). There is no published information on this condition in China. To ascertain the prevalence of diastolic heart failure in this community, 200 consecutive patients with the typical features of congestive heart failure were studied with standard 2-dimensional Doppler echocardiography. A LV ejection fraction (LVEF) >45% was considered normal. The results showed that 12.5% had significant valvular heart disease. Of the remaining 175 patients, 132 had a LVEF >45% (75%). Therefore, 66% of patients with a clinical diagnosis of heart failure had a normal LVEF. Heart failure with normal LV systolic function was more common than systolic heart failure in those >70 years old (65% vs 47%; p = 0.015). Most (57%) had an abnormal relaxation pattern in diastole and 14% had a restrictive filling pattern. In the systolic heart failure group, a restrictive filling pattern was more common (46%). There were no significant differences in the sex distribution, etiology, or prevalence of LV hypertrophy between these 2 heart failure groups. In conclusion, heart failure with a normal LVEF or diastolic heart failure is more common than systolic heart failure in Chinese patients with the symptoms of heart failure. This may be related to older age at presentation and the high prevalence of hypertension in this community.

Chondroitin sulfate in palatal wound healing.

Chondroitin sulfate is up-regulated in granulation tissue during wound healing. To investigate the role of chondroitin sulfate in the wound-healing process after surgical repair of cleft palate, we isolated and cultured rabbit palatal fibroblasts. Treatment with chondroitin-6-sulfate resulted in a dose-dependent increase in cell adhesion and cell proliferation, whereas the reverse effects were seen after chondroitinase degradation of chondroitin sulfate. The biological actions of chondroitin sulfate appeared to be dependent on the presence and position of sulfate groups. Inhibition of glycosaminoglycan sulfation by chlorate treatment led to reduced cell adhesion and cell proliferation and a slower rate of wound closure in vitro. Furthermore, exposure to chondroitin-4-sulfate resulted in a dose-dependent reduction in cell adhesion. Together, these results show that chondroitin sulfate is involved in palatal wound healing.