[Clinicopathological features of Helicobacter pylori-negative early gastric cancer].

OBJECTIVE: To investigate the clinicopathological features of Helicobacter pylori (Hp)-negative early gastric cancer. METHODS: The clinicopathological data of 30 cases of Hp-negative early gastric cancer were collected retrospectively at Pingdingshan Medical District, 989 Hospital of PLA Joint Logistics Support Force, and Beijing Chaoyang Hospital, Capital Medical University, from 2009 to 2021, and the histomorphological characteristics and immunophenotype were observed, and combined with the literature to explore. RESULTS: The median age of 30 patients was 58.5 years (range: 21-80 years), including 13 males and 17 females. The upper part of the stomach was 13 cases, the middle part of the sto-mach was 9 cases, and the lower part of the stomach was 8 cases. The median diameter of the tumor was 11 mm (range: 1-30 mm). According to the Paris classification, 9 cases were 0-Ⅱa, 7 cases were 0-Ⅱb, and 14 cases were 0-Ⅱc. Endoscopic examination showed that 18 cases of lesions were red, 12 cases of lesions were faded or white, and microvascular structures and microsurface structures were abnormal. In all the cases, collecting venules were regularly arranged in the gastric body and corner mucosa. There were 18 cases of well differentiated adenocarcinoma in the mucosa. The tumor presented glandular tubular-like and papillary structure, with dense glands and disordered arrangement; the cells were cuboidal or columnar, with increased nuclear chromatin and loss of nuclear polarity, and most of them expressed gastric mucin. Signet-ring cell carcinoma was found in 7 cases, all the cancer tissues were composed of signet-ring cells, and the cancer cells were mainly distributed in the middle layer to the surface layer of mucosa. Gastric oxyntic gland adenoma (gastric adenocarcinoma of the fundic gland type confined to mucosa) in 2 cases, gastric adenocarcinoma of the fundic gland type in 2 cases, and gastric adenocarcinoma of fundic gland mucosa type in 1 case. The tumor tissue was composed of branching tubular glands, except 1 case of mucosal surface epithelium was partially neoplastic, the other 4 cases of mucosal surface epi-thelium were all non-neoplastic; the cells were arranged in a single layer, and the nucleus was close to the basal side, and the nucleus was only slightly atypical. Pepsinogen I and H+/K+ ATPase were positive in 5 cases of gastric fundus gland type tumors, and 1 case of foveolar-type tumor cells at the surface and depth of mucosa showed MUC5AC positive. The gastric mucosa adjacent to cancer was generally normal in all cases, without atrophy, intestinal metaplasia and Hp. CONCLUSION: Hp-negative early gastric cancer is a heterogeneous disease group with various histological types, and tubular adenocarcinoma and signet-ring cell carcinoma are common. Tubular adenocarcinoma mostly occurs in the elderly and the upper to middle part of the stomach, while signet-ring cell carcinoma mostly occurs in young and middle-aged people and the lower part of the stomach. Gastric neoplasm of the fundic gland type is relatively rare.

[Clinicopathological features of verrucous type dysplasia of esophagus].

Objective: To investigate the clinicopathological features of verrucous type (squamous) dysplasia of esophagus. Methods: The clinicopathological data of 18 verrucous type dysplasia of esophagus patients in the 989th Hospital of the Joint Logistics Support Force of the People's Liberation Army (formerly 152 Central Hospital) and Beijing Chaoyang Hospital Affiliated to Capital Medical University from 2009 to 2021 were retrospectively collected. The histomorphologic characteristics and immunophenotype were observed, and human papillomavirus (HPV) genotyping was detected by PCR-fluorescence probe. The relevant literature was reviewed. Results: The median age of the 18 patients was 68 years (range 53-76 years); there were 13 males and 5 females. There were four cases in the upper esophagus, seven in the middle esophagus and seven in the lower esophagus. The median diameter of the lesion was 18 mm (range 6-54 mm). According to the Paris Classification, 11 cases were 0-Ⅱa, one case was 0-Ⅱa+Ⅰ, five cases were 0-Ⅱb, and one case was 0-Ⅱb+Ⅰ. White light endoscopy showed that the surface of the lesion was white plaque, red areas between the plaques, and papillary surface structure could be seen. In narrow-band imaging, some mucosal areas of lesions were opaque or patchy and light brown, and papillary microsurface structures were different in shapes and sizes. Intraepithelial microvessels were elongated, dilated, twisted and varied in diameter. Lugol iodine stain showed nil to faint staining. Histologically, the atypia cells were large with rounded to irregular nuclei, coarse chromatin, mitotic figures, and abundant eosinophilic cytoplasm. The basal cells showed increased atypia, crowding, increased nuclear-cytoplasmic ratio, and active mitosis. The cells were arranged haphazardly. Single cell keratinization, binuclear cells, and hollow-out-like cells, as well as surface epithelial keratinization and parakeratosis were observed in three cases. There were obvious verrucous or papillary structures in the epithelial layer. Five patients had local verrucous carcinoma. Immunohistochemical staining showed that the mutant expression of p53 protein in 6/10 cases; p16 was positive in 5/10 cases; abnormal Ki-67 distribution pattern in 10/10 cases. HPV was negative in all 10 cases tested. The original pathologic diagnosis of preoperative biopsy was high-grade dysplasia in 8 cases, low-grade dysplasia in 6 cases and atypical squamous epithelial cells in 4 cases. Conclusions: Esophageal verrucous dysplasia tumor cells are well differentiated with obvious verrucous or papillary structures. The unique morphological features suggest that it represents a histological subtype of esophageal squamous high-grade dysplasia and it is a precursor of verrucous carcinoma. Its preoperative biopsy diagnosis is challenging.

[Changes of cytokines in the aqueous humor of neovascular glaucoma at the angle-closure stage].

Objective: To evaluate the concentration of cytokines in the aqueous humor of neovascular glaucoma (NVG) patients at the angle-closure stage in different treatment periods and its relationship with recurrence. Methods: A prospective case-control study. Angle-closure stage NVG patients who came to Peking University Third Hospital from September 2018 to September 2019 were enrolled and followed-up for at least 12 months. Patients received triple sequential therapy, including anti-vascular endothelium growth factor (VEGF) injection, trabeculectomy, and panretinal photocoagulation. The aqueous humor before anti-VEGF treatment, before trabeculectomy, and during recurrence was collected. Multiplex bead immunoassay was applied to measure the concentration of 45 cytokines including VEGF, interleukin (IL), and chemokine. The relevant data were compared with the values of 25 proliferative diabetic retinopathy (PDR) patients and 24 age-related cataract patients undergoing phacoemulsification as controls. The concentration of cytokines was presented as M (Q1, Q3). The nonparametric Kruskal-Wallis H test was applied to compare the cytokine concentration between the NVG group and controls. The difference between the recurrence and non-recurrence groups was compared with the Mann-Whitney U test. Results: The average age of NVG patients was (60±11) years, and there were 22 males and 10 females. No significant differences were found in age and gender between the NVG group and the two control groups (both P>0.05). The median concentrations of VEGF in the NVG group before anti-VEGF treatment, before trabeculectomy, and after recurrence were 2 151.3 (1 433.1, 4 280.0) ng/L, 655.4 (287.3, 836.3) ng/L and 2 003.4 (1 603.1, 2 468.9) ng/L respectively. The concentrations of VEGF before anti-VEGF treatment and after recurrence in the NVG group were significantly higher than the PDR group [453.8 (189.9, 595.8) ng/L] and the cataract group [143.5 (112.7, 269.8) ng/L] (all P<0.05). The median concentration of programmed cell death protein ligand 1 (PD-L1) was 38.9 (22.4, 50.6) ng/L before anti-VEGF treatment, higher than that in the PDR group [12.0 (6.3, 20.1) ng/L] and the cataract group [14.6 (11.4, 19.3) ng/L]. The median concentration of fractalkine was 242.7 (189.0, 306.7) ng/L, higher than that in the PDR group [131.1 (119.1, 157.6) ng/L] and the cataract group [116.7 (10.2, 135.9) ng/L]. The median concentration of IL-7 was 18.0 (12.0, 32.7) ng/L, higher than that in the PDR group [7.7 (2.0, 10.8) ng/L] and the cataract group [3.3 (1.9, 6.8) ng/L]. The median concentration of eotaxin was 84.0 (52.4, 122.7) ng/L, higher than that in the PDR group [26.6 (17.1, 72.3) ng/L] and the cataract group [7.1 (5.6, 14.8) ng/L]. The median concentration of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was 3.6 (2.8, 6.4) ng/L, higher than that in the cataract group [1.1 (0.3, 2.3) ng/L]. All the differences were statistically significant (all P<0.05). There were no significant differences between the NVG and control groups in other cytokines or other treatment periods (all P>0.05). Six NVG patients suffered recurrence during the follow-up. The baseline concentration of IL-7 of these patients [10.5 (8.4, 16.0) ng/L] was significantly lower than that in patients who did not have recurred disease [22.7 (15.7, 34.1) ng/L] (Z=-2.74, P<0.01). Conclusions: In the angle-closure stage of NVG patients, the concentrations of VEGF, PD-L1, fractalkine, IL-7, eotaxin, and TRAIL in the aqueous humor significantly increase during the onset of disease. Lower IL-7 may indicate a recurring tendency.

[Pathological characteristics of colorectal adenoma with submucosal pseudoinvasion].

Objective: To investigate the pathomorphological characteristics of colorectal adenoma with submucosal pseudoinvasion and to summarize the corresponding pseudoinvasion patterns. Methods: The clinicopathological data of 9 cases of colorectal adenoma were collected at 989 Hospital of PLA Joint Logistics Support Force (4 cases) and Beijing Chaoyang Hospital, Capital Medical University (5 cases), from 2016 to 2019. retrospectively, and the histomorphological characteristics and immunophenotypes were analyzed, and discussed in light of the relevant literature. Results: There were 8 cases of adenoma with stalk. Tumor glands were found in the submucosa at the head end of adenoma, similar to infiltrating adenocarcinoma. The structure and cellular morphology of submucosal glands were very similar to the intramucosal tumor while the local submucosal tumor showed continuity with the intramucosal tumor. The submucosal tumors were lobule-like or nest-like with clear boundary. The outline of the gland was smooth and blunt-round, and there was loose fibromyxoid stroma around the gland, similar to the mucosa propria stroma. Some cases of the submucosal glands were cystic dilated with mucocele formation and hemosiderin deposition. One case with broad stalk-base showed an elevated adenoma with local high grade dysplasia involved in the aggregated lymphoid nodule, forming the lymphoglandular complexes, simulating invasive adenocarcinoma with associated submucosal lymphoid aggregates. Submucosal cancer tissue and intramucosal cancer tissue had continuity, and their morphology was the same. The submucosal tumor was round in the outline, smooth and blunt in the edge, and surrounded by lymphoid tissue. There was no stromal response around the gland to promote the proliferation of connective tissue, neither was there single-cell or small-cell cluster, sharp angle branch of gland, or vascular infiltration. Conclusions: There are two unique morphological patterns in colorectal adenoma with submucosal pseudoinvasion. Morphologically, the data show that one is lobular-like pattern, and the other is lymphoglandular complexes-like pattern. The main features of the two patterns are the same-morphology and continuity of submucosal tumor and intramucosal tumor. The pushed glands were surrounded by the intrinsic membrane stroma and muscularis mucosae in proper order, lacking the typical morphological characteristics of invasive adenocarcinoma.

Comparison of mode of failure between primary and revision total knee arthroplasties.

INTRODUCTION: Cognizance of common reasons for failure in primary and revision TKA, together with their time course, facilitates prevention. However, there have been few reports specifically comparing modes of failure for primary vs. revision TKA using a single prosthesis. The goal of the study was to compare the survival rates, modes of failure, and time periods associated with each mode of failure, of primary vs. revision TKA. HYPOTHESIS: The survival rates, modes of failure, time period for each mode of failure, and risk factors would differ between primary and revision TKA. MATERIAL AND METHODS: Data from a consecutive cohort comprising 1606 knees (1174 patients) of primary TKA patients, and 258 knees (224 patients) of revision TKA patients, in all of whom surgery involved a P.F.C® prosthesis (Depuy, Johnson & Johnson, Warsaw, IN), was retrospectively reviewed. The mean follow-up periods of primary and revision TKAs were 9.2 and 9.8 years, respectively. RESULTS: The average 10- and 15-year survival rates for primary TKA were 96.7% (CI 95%,±0.7%) and 85.4% (CI 95%,±2.0%), and for revision TKA 91.4% (CI 95%,±2.5%) and 80.5% (CI 95%,±4.5%). Common modes of failure included polyethylene wear, loosening, and infection. The most common mode of failure was polyethylene wear in primary TKA, and infection in revision TKA. The mean periods (i.e., latencies) of polyethylene wear and loosening did not differ between primary and revision TKAs, but the mean period of infection was significantly longer for revision TKA (1.2 vs. 4.8 years, P=0.003). DISCUSSION: Survival rates decreased with time, particularly more than 10 years post-surgery, for both primary and revision TKAs. Continuous efforts are required to prevent and detect the various modes of failure during long-term follow-up. Greater attention is necessary to detect late infection-induced failure following revision TKA. LEVEL OF EVIDENCE: Case-control study, Level III.

Pre-operative features of non-invasive follicular thyroid neoplasms with papillary-like nuclear features: An analysis of their cytological, Gene Expression Classifier and sonographic findings.

OBJECTIVE: To investigate the corresponding cytological diagnoses, Gene Expression Classifier (GEC) results and ultrasound features of thyroid nodules diagnosed as non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), as well as any coexisting pathology. METHODS: We performed a retrospective review of thyroid nodules histologically diagnosed as NIFTP at our institution between 1st April 2016 and 1st April 2017. The following data points were collected: demographics, nodule size, ultrasound features, cytological diagnosis, GEC results, origin of sample (in-house vs outside hospital) and any additional pathology identified in the resection specimen. RESULTS: The case cohort included 87 nodules diagnosed as NIFTP (size range: 1-7 cm, mean: 2.5 cm) from 82 patients (age range: 22-82, mean age: 50.4, M:F-1:4.1). Corresponding FNA results were available for 72 nodules (82.8%) and were categorised as follows: benign (n = 5, 6.9%), atypia of unknown significance/follicular lesion of undetermined significance (n = 29, 40.3%), follicular neoplasm/suspicious for follicular neoplasm/follicular neoplasm with oncocytic features (n = 27, 37.5%), suspicious for papillary thyroid carcinoma (n = 6, 8.3%) and malignant (n = 5, 6.9%). GEC results were available for 32 (44.4%) nodules, with the majority of cases classified as suspicious (81.3%). On ultrasound, most of the nodules were predominantly solid (81.8%), vascular (93.8%), non-calcified (86.5%), and either hypoechoic (44.9%) or isoechoic (38.8%). In addition to NIFTP and other benign findings in the background thyroid, 75 separate malignant tumours were identified in 38 (46.3%) patients, many of which were papillary thyroid microcarcinomas (86.5%) with lymph node metastases present in two cases. CONCLUSIONS: The majority of thyroid nodules histologically diagnosed as NIFTP have indeterminate cytology (77.8%) and are classified as suspicious (81.3%) by GEC testing. Taken together, these findings can guide clinicians toward a more conservative therapeutic approach.

A novel synthetic compound, 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione, inhibits cisplatin-induced hearing loss by the suppression of reactive oxygen species: in vitro and in vivo study.

Cisplatin, a chemotherapeutic agent for treating various solid tumors, produces hearing loss in approximately half a million cancer patients annually in the United States. In the course of developing a new protective agent against cisplatin-induced ototoxicity, we have been interested in a novel synthetic compound, 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR-22332). The effect of KR-22332 on cisplatin-induced cytotoxicity was analyzed in vitro in an organ of Corti-derived cell line (HEI-OC1), and in vivo in a zebrafish and rat model. Cisplatin-induced apoptosis, reactive oxygen species (ROS) generation and altered mitochondrial membrane potential (MMP) in HEI-OC1 cells were observed. KR-22332 significantly inhibited cisplatin-induced apoptosis, change of MMP, and intracellular ROS generation. KR-22332 markedly attenuated the cisplatin-induced loss and changes of auditory neuromasts in the zebrafish. Transtympanic administration of KR-22332 in a rat model was protective against cisplatin-induced hearing loss, as determined by click-evoked auditory brainstem response (p<0.01). Tissue terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of rat cochlea demonstrated that KR-22332 blocked cisplatin-induced apoptosis. In addition, transtympanic administration of KR-22332 inhibited cisplatin-induced nicotinamide adenine dinucleotide phosphate-oxidase 3 (NOX3) overexpression in the rat cochlea. KR-22332 significantly reduced the expression of p-53, mitogen-activated protein kinases, caspase 3, and tumor necrosis factor-α compared to their significant increase after cisplatin treatment. The results of this study suggest that KR-22332 may prevent ototoxicity caused by the administration of cisplatin through the inhibition of mitochondrial dysfunction and the suppression of ROS generation. These novel findings implicate KR-22332 as a potential candidate for protective agent against cisplatin-induced ototoxicity.

Serum 1,5-anhydroglucitol is associated with diabetic retinopathy in Type 2 diabetes.

AIMS: To determine whether there is a relationship between 1,5-anhydroglucitol (1,5-AG), a marker of postprandial hyperglycaemia and glycaemic variability, and the presence of diabetic retinopathy and albuminuria in patients with Type 2 diabetes. METHODS: Five hundred and sixty-seven patients with Type 2 diabetes (serum creatinine < 133 µmol/l), who were enrolled in the Seoul Metro-City Diabetes Prevention Program (SMC-DPP), were cross-sectionally assessed by multivariate logistic regression analysis. RESULTS: After controlling for age, sex, binary HbA(1c) levels, duration of diabetes, triglyceride, systolic blood pressure, smoking status, history of hypertension and dyslipidaemia, and the use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker medication, the odds ratios (95% CI) of diabetic retinopathy were 2.86 (1.12-7.25) for the first (lowest) quartile of 1,5-anhydroglucitol, 2.87 (1.25-6.61) for the second quartile and 0.88 (0.35-2.22) for the third quartile compared with the fourth quartile (P for trend = 0.010). Conversely, the associations between 1,5-anhydroglucitol and clinical albuminuria were non-significant after adjustment. Subjects with low 1,5-anhydroglucitol (< 10.0 µg/ml) were more likely to experience diabetic retinopathy than those with high 1,5-anhydroglucitol (≥ 10.0 µg/ml) under moderate glucose control (HbA(1c) < 8%, 64 mmol/mol) and there were no significant differences in the prevalence of diabetic retinopathy between the subgroup with HbA(1c) < 8% (64 mmol/mol) and low 1,5-anhydroglucitol and the subgroup with HbA(1c) ≥ 8% (64 mmol/mol). CONCLUSIONS: 1,5-Anhydroglucitol levels show close associations with diabetic retinopathy, especially among patients under moderate glucose control, but not with albuminuria. These results suggest that 1,5-anhydroglucitol might be a complementary marker for targeting higher risk group.

Closed-wedge high tibial osteotomy using computer-assisted surgery compared to the conventional technique.

We assessed the reliability, accuracy and variability of closed-wedge high tibial osteotomy (HTO) using computer-assisted surgery compared to the conventional technique. A total of 50 closed-wedge HTO procedures were performed using the navigation system, and compared with 50 HTOs that had been performed with the conventional technique. In the navigation group, the mean mechanical axis prior to osteotomy was varus 8.2 degrees, and the mean mechanical axis following fixation was valgus 3.6 degrees. On the radiographs the mean pre-operative mechanical axis was varus 7.3 degrees, and the mean post-operative mechanical axis was valgus 2.1 degrees . There was a positive correlation between the measured data taken under navigation and by radiographs (r > 0.3, p < 0.05). The mean correction angle was significantly more accurate in the navigation group (p < 0.002). The variability of the correction was significantly lower in the navigation group (2.3 degrees vs 3.7 degrees , p = 0,012). We conclude that navigation provides reliable real-time intra-operative information, may increase accuracy, and improves the precision of a closed-wedge HTO.

Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1-S transition.

The tumor suppressor RASSF1A is inactivated in many human cancers and is implicated in regulation of microtubule stability, cell cycle progression and apoptosis. However, the precise mechanisms of RASSF1A action and their regulation remain unclear. Here we show that Skp2, an oncogenic subunit of the Skp1-Cul1-F-box ubiquitin ligase complex, interacts with, ubiquitinates, and promotes the degradation of RASSF1A at the G1-S transition of the cell cycle. This Skp2-dependent destruction of RASSF1A requires phosphorylation of the latter on serine-203 by cyclin D-cyclin-dependent kinase 4. Interestingly, mutation of RASSF1A-phosphorylation site Ser(203) to alanine results in a delay in cell cycle progression from G1 to S phase. Moreover, enforced expression of Skp2 abolishes the inhibitory effect of RASSF1A on cell proliferation. Finally, the delay in G1-S progression after Skp2 removal is normalized by depletion of RASSF1A. These findings suggest that the Skp2-mediated degradation of RASSF1A plays an important role in cell proliferation and survival.

A new sesquiterpene lactone glucoside with inhibitory effect on K562 cells from Ixeris sonchifolia (Bge) Hance.

A new minor sesquiterpene lactone glucoside, ixerin ZA (1), together with 16 known compounds, were isolated from the whole plants of Ixeris sonchifolia (Bge) Hance. The structure of 1 was elucidated as 1(10),3,11(13)-guaiatriene-12,6-olide-2-one-3-O-[6'-(p-metheoxyphenylacetyl)]-beta-glucopyranoside on the basis of spectroscopic and chemical evidence. Compound 1 exhibited an inhibitory effect on K562 cells.

Temporal expression of proteoglycans in the rat limb during bone healing.

Proteoglycans found in the bone extracellular matrix and on the cell surface can complex with HBGFs such as the FGFs, TGFs and BMPs which are known to play key roles in regulating fracture healing. Here we have studied the expression of key PGs during the bone repair process in order to determine the relationship between PG expression and healing status. We created non-critical sized trephine defects just proximal to the distal end of the tibial crest of adult male Wistar rats and examined the healing process histologically as well as by monitoring the temporal expression of mRNA transcripts for ALP, OP and OC, together with HSPG, CSPG and FGF-FGF receptor expression. Following surgery, animals were allowed to recover, and then euthanized after 7, 14, 21 and 28 days post-surgery, at which time tissue was harvested for histological examination and total RNA extracted and the mRNA transcripts examined by quantitative real-time PCR. HS and CSPG expression was generally observed to increase in the days immediately following injury, reaching peak expression two weeks post-surgery. This was followed by a gradual return to basal levels by day 28. The expression patterns of PGs were broadly similar with those of ALP, OP and FGFRs. The increase of mRNA expression for many key PGs detected during bone healing coincided with the elevation of bone markers and FGFRs, and provides further evidence that PGs involved in bone repair act in part through susceptible growth factors, including the FGF/FGFR system. The data presented here indicates that increased proteoglycan expression is involved in the early stages of bone healing at a time when previous studies have shown that the levels of HBGFs are maximal. Hence there exists a rationale for an exploration of the use of exogenous PGs as an adjunct therapy to potentiate the powerful effects of these factors and to augment the natural healing response.

Four peptide hormones' specific decrease (up to 97%) of human prostate carcinoma cells.

BACKGROUND: Mortality from prostate cancer remains a significant problem with current treatment(s), with an expected 30 350 deaths from prostate cancer in 2005. Long-acting natriuretic peptide, vessel dilator, kaliuretic peptide and atrial natriuretic peptide have significant anticancer effects in breast and pancreatic adenocarcinomas. Whether these effects are specific and whether they have anticancer effects in prostate adenocarcinoma cells has not been determined. MATERIALS AND METHODS: These peptide hormones were evaluated to determine if they have specific anticancer effects in human prostate adenocarcinomas. RESULTS: Dose-response curves revealed a significant (P < 0.05) decrease in human prostate cancer number with each tenfold increase in the concentration from 1 microM to 1000 microM (i.e. 1 mM) of these four peptide hormones. There was a 97.4%, 87%, 88% and 89% (P < 0.001 for each) decrease in prostate cancer cells secondary to vessel dilator, long-acting natriuretic peptide, kaliuretic peptide and atrial natriuretic peptide, respectively, at their 1-mM concentrations within 24 h, without any proliferation in the 3 days following this decrease. These same hormones decreased DNA synthesis from 68% to 89% (P < 0.001). When utilized with their respective antibodies their ability to decrease prostate adenocarcinoma cells or inhibit their DNA synthesis was completely blocked. Western blots revealed that for the first time natriuretic peptide receptors (NPR) A- and C- were present in prostate cancer cells. CONCLUSIONS: These results indicate that these peptide hormones' anticancer effects are specific. Furthermore, they have very potent effects of eliminating up to 97% of prostate cancer cells within 24 h of treatment.

Total knee arthroplasty in stiff knees after previous infection.

Between July 1986 and August 1996, we performed 32 total knee arthroplasties (TKA) on 32 patients with partially or completely ankylosed knees secondary to infection. Their mean age at surgery was 40 years (20 to 63) and the mean follow-up was ten years (5 to 13). The mean post-operative range of movement was 75.3 degrees (30 to 115) in those with complete and 98.7 degrees (60 to 130) in those with partial ankylosis. The mean Hospital for Special Surgery knee score increased from 57 to 86 points post-operatively. There were complications in four knees (12.5%), which included superficial infection (one), deep infection (one), supracondylar femoral fracture (one) and transient palsy of the common peroneal nerve (one). Although TKA in the ankylosed knee is technically demanding and has a considerable rate of complications, reasonable restoration of function can be obtained by careful selection of patients, meticulous surgical technique, and aggressive rehabilitation.

Secondary insults and outcomes in patients with hypertensive basal ganglia hemorrhage.

This study was designed to monitor secondary insults and their impact on outcomes of patients with hypertensive basal ganglia hemorrhage (HBGH). One hundred and twelve patients with HBGH (male 73, female 39) of age 42 +/- 8 years (range from 38 to 57 years) were studied. Operations included craniotomy or trephination drainage with urokinase thrombolysis. Conventional therapies were also given to the patients including the administration of mannitol, crystalloid and colloid solution. In the meantime, blood pressure (MAP), temperature (T) and SaO2 and other parameters were recorded in the intensive care unit. The ICP values were recorded, and the early clinical outcome was assessed upon discharge according to Glasgow Outcome Scale. Cerebral Perfusion Pressure was calculated as CPP = MAP-MICP. Outcomes in the group without secondary insults were better than that in the group with secondary insults (P < 0.01). No unfavorable outcomes were found in the 59 cases managed by ultra-early surgery whereas 36.1% of the cases operated after 6 hours of onset had unfavorable outcomes. It is concluded that the high incident rate of secondary insults in HICH patients influences outcome. Ultra-early surgery may also contribute to improved quality of survival.

Studies on the receptors mediating responses of osteoblasts to thrombin.

The serine protease thrombin stimulates proliferation in osteoblasts, but decreases alkaline phosphatase (ALP) activity, a marker of osteoblast differentiation. Three thrombin receptors have been identified, protease activated receptor (PAR)-1, PAR-3 and PAR-4; we have previously demonstrated that mouse osteoblasts express PAR-1 and PAR-4. The effect of thrombin on osteoblast proliferation and differentiation was studied to determine which of the thrombin receptors is responsible for the primary effects of thrombin. Primary mouse calvarial osteoblasts from PAR-1-null and wild-type mice, and synthetic peptides that specifically activate PAR-1 (TFFLR-NH2) and PAR-4 (AYPGKF-NH2) were used. Both the PAR-1-activating peptide and thrombin stimulated incorporation of 5-bromo-2'-deoxyuridine (two to four-fold, P < 0.001) and reduced alkaline phosphatase activity (approximately three-fold, P < 0.05) in cells from wild-type mice. The PAR-4-activating peptide, however, had no effect on either alkaline phosphatase activity or proliferation in these cells. Neither thrombin nor PAR-4-activating peptide was able to affect osteoblast proliferation or alkaline phosphatase activity in cells isolated from PAR-1-null mice. The results demonstrate that thrombin stimulates proliferation and inhibits differentiation of osteoblasts through activation of PAR-1. No other thrombin receptor appears to be involved in these effects.

Outcome following addition of peroneus brevis tendon transfer to treatment of acquired posterior tibial tendon insufficiency.

The flexor digitorum longus, the tendon most often used for transfer in posterior tibial tendon insufficiency, is one-half to one-third the size of the posterior tibial tendon. Occasionally it may be particularly small or may have been previously used for transfer. In these cases, the senior author has felt that the addition of a transfer of the Peroneus Brevis (PBr) tendon may be helpful in maintaining sufficient tendon and muscle mass to rebalance the foot. Thirteen patients who underwent this procedure were retrospectively identified and matched by age and length of follow-up to patients who underwent a more standard tendon transfer operation minus the addition of the PBr transfer. Pain and functional status were then assessed by the American Orthopaedic Foot and Ankle Society's ankle/hindfoot rating scale. Each patient was tested by an independent physical therapist to evaluate inversion and eversion strength. The mean duration of follow-up was 20.6 months (12 to 34 months). The average AOFAS score of the PBr group was 75.8 compared to 71.5 for the standard control group. There was no significant difference between the groups when inversion or eversion strengths were compared. Inversion strength and eversion strength was rated good or excellent (4 or 5) in 12 out of 13 of the PBr transfer group patients. No major complications were encountered in either group. Although it does not increase inversion strength, a PBr transfer can be used to augment a small FDL without causing significant eversion weakness. This can be useful when the FDL is particularly small or in revision surgery.

A second look at the embryotoxicity of hydrosalpingeal fluid: an in-vitro assessment in a murine model.

The purpose of this study was to evaluate whether hydrosalpingeal fluid (HSF) is toxic to the mouse embryo as assessed by the blastocyst development rate (BDR) and by cell counting in vitro. HSF was collected from nine patients undergoing salpingoneostomy to correct hydrosalpinx. Two-cell embryos were obtained from superovulated ICR mice. T6 medium and T6 + 0.4% bovine serum albumin (BSA) were used as control media. T6 medium containing 10% or 50% HSF and 100% HSF from each patient were used as test media. Nine to 15 embryos were cultured in microdrops prepared from each of these media. The BDR was examined after 72 h of culture in these media. To assess the total cell number within each blastocyst, the blastocysts were fixed and stained with Hoechst 33342 to facilitate cell counting. The BDR was affected adversely only by 100% HSF and not in media containing 10% or 50% HSF. The mean BDR using T6 medium and T6 + BSA were 88.7% and 85.3%, respectively. The mean BDR using media containing 10% HSF or 50% HSF were 90.0% and 89.4%, respectively. Mean BDR using 100% HSF was 75.2% (P < 0.05). The overall mean cell counts (+/- SEM) using T6 medium and T6 + BSA were 86.9+/-3.2 and 91.0+/-3.8 respectively. Mean cells counts were decreased significantly only in blastocysts cultured in 100% HSF (63.3+/-4.6; P < 0.01) but not in blastocysts cultured in 10% or 50% HSF (90.8+/-4.2 and 81.9+/-6.1 respectively). Thus, it is concluded that HSF has no embryotoxic effect but has a mildly negative effect on embryonic growth and development.

[An immunohistochemical study on megakaryocytes in patients with myelodysplastic syndromes].

An immunohistochemical study was performed on trephine biopsy specimens of bone marrow in 10 patients with myelodysplastic syndromes (MDS). Monoclonal antibodies HIP7 and CDW41 were used against platelet glycoprotein IIb/IIIa (CD41) to determine dysmegakaryopoiesis including its size, proportion of micromegakaryocytes, location and staining characteristics. The results show that the dysmegakaryopoiesis of MDS includes the increased number and high proportion of micromegakaryocytes, the altered architectural distribution and the considerable variation in staining. These may be helpful in the diagnosis and differential diagnosis of MDS.