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Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal cancer.

The expression of CD44v6 is well known as a useful marker of tumor progression and prognosis in colorectal cancer. In this study, we evaluated the serum levels of soluble CD44 splice variants containing exon v6 (sCD44v6) and examined the histological expression of CD44v6 in patients with colorectal cancer. Serum samples were obtained from 44 primary colorectal cancer patients before surgery. We used enzyme-linked immunosorbent assay to determine the serum levels of sCD44v6. The expression of CD44v6 was examined by immunohistochemical staining of the primary tumors obtained from the same patients. Both the serum concentration of sCD44v6 and the expression of CD44v6 were significantly associated with lymph node metastasis (p < 0.05). Furthermore, the serum level of sCD44v6 was higher in those patients with CD44v6-positive tumor tissues (154.4 +/- 34.8 ng/ml) than in those with CD44v6-negative ones (130.7 +/- 32.3 ng/ml; p < 0.05). The 5-year survival rate was significantly lower in patients with high serum levels of sCD44v6 (52.4%) than in those with low levels of sCD44v6 (78.0%; p < 0.05), and it was also significantly lower in patients with CD44v6-positive cancer (42.1%) than in those with CD44v6-negative cancer (84%; p < 0. 01). We concluded that preoperative elevation in the serum levels of sCD44v6 might be a prognostic indicator for patients with colorectal cancer.

Adenocarcinoma↗

Serum vascular endothelial growth factor as a possible prognostic indicator in sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder of unknown etiology, which involves the lung, eye, liver, and other organs. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis involved in an important role in the development of granuloma. However, only a limited number of studies have reported on the relationship between serum VEGF values and the clinical status of sarcoidosis. Concentrations of serum VEGF were determined in 33 patients with sarcoidosis. We investigated the correlation between serum VEGF values and extent of disease, prognosis, and radiographic stage compared with serum angiotensin converting enzyme (ACE) values as another candidate. Concentrations of serum VEGF in patients who received corticosteroid treatment were significantly higher than those of patients with spontaneous remission (p < 0.05). In addition, serum VEGF values in patients with extrathoracic involvements were significantly higher than those of patients with sarcoid lesions limited to the thoracic space (p < 0.05), accompanied by a tendency to increase the number of organs involved. The values of serum ACE revealed no relationship to the values of serum VEGF, administration of corticosteroid, or extrathoracic involvements. We concluded that serum VEGF values in patients with sarcoidosis is a predictive factor in determining extrathoracic organ involvements and as a parameter for deciding the necessity of treatment with corticosteroid. Serum VEGF might be a useful marker as a prognostic indicator in sarcoidosis.

Adrenal Cortex Hormones↗

High bax expression is a good prognostic indicator in acute myeloid leukaemia.

Most cytotoxic drugs kill cells by instigating the process of apoptosis and it has been suggested that apoptotic markers may provide an indication of tumour chemosensitivity. The aim of this study was to determine if such a relationship exists in acute myeloid leukaemia (AML). The levels of spontaneous apoptosis, bcl-2 and bax were evaluated in 56 newly diagnosed AML patients to determine if they correlated with a response to cytotoxic therapy. Spontaneous apoptosis was lower, but bcl-2, bax and the bcl-2/bax ratio were higher in AML compared with normal individuals. AML patients with high bax expression at diagnosis had significantly better prognosis for disease-free survival, event-free survival and overall survival (P = 0.016). In the standard risk group, high bax expression was in keeping with significantly improved survival. Multivariate analysis revealed bax to be an independent predictor of survival. There was a significant reduction in bcl-2 and bax expression when AML patients entered complete remission and also in relapsed AML patients who entered a second remission. This study suggests that bax is a useful prognostic indicator in AML and may assist with therapeutic decision-making for patients in the standard risk category.

Acute Disease↗

Importance of metabolic monitoring systems as an early prognostic indicator in severe head injured patients.

We have analyzed and evaluated what is the best metabolic monitoring system to determine the prognosis for maintenance of neurological function in severe head injured patients. Acute subdural hematoma (ASDH) was recognized in fifteen of 22 patients and cerebral contusion in seven in this series. Intracranial pressure (ICP), jugular venous pH and jugular bulb venous oxygen saturation (SjO2) were continuously monitored as soon as possible following stabilization. The measurement of cerebral blood flow (CBF) was carried out using a stable Xenon-computerized tomography (Xe-CT). After measuring CBF, 3% carbon dioxide (CO2) loading was conducted to determine CO2 responses (delta CBF/delta CO2). In patients who died (D), jugular venous pH showed evidence of acidosis (6.3-7.2) with delta CBF/delta CO2 < 1 and cerebral metabolic rate of oxygen (CMRO2) < 1.21 within several hours of the trauma. On the other hand, arterial pH was shown to be within the normal range. In vegetative state (VS) and severe disability (SD) patients, jugular venous pH was shown to be within normal range, with delta CBF/delta CO2 < 1 and 1.44 < CMRO2 < 1.79. In all of moderate disability (MD) and good recovery (GR) patients, jugular venous pH was shown to be within the normal range, with delta CBF/delta CO2 > 1 and 1.65 < CMRO2 < 1.85. These results suggest that jugular venous pH, CO2 response and CMRO2, were useful as early prognostic indicators in the maintenance of neurological function.

Acidosis↗

Angiogenesis and blood vessel invasion as prognostic indicators for node-negative breast cancer.

This study was undertaken to determine the value of angiogenesis and blood vessel invasion (BVI) using both Factor VIII-related antigen and elastica van Gieson staining in predicting 20-year relapse-free survival (RFS) and 20-year overall survival (OS) rates in Japanese patients with node-negative breast cancer. Two hundred and sixty patients were studied. We investigated nine factors, including angiogenesis (average microvessel count (AMC)), BVI, proliferating cell nuclear antigen (PCNA), p53, c-erbB-2, clinical tumor size (T), histological grade, tumor necrosis, and lymphatic vessel invasion (LVI). Twenty-five patients (9.6%) had recurrence and 17 patients (6.5%) died of breast cancer. Univariate analysis showed that BVI, AMC, T, histological grade, PCNA, p53, and tumor necrosis were significantly predictive of RFS or OS. Multivariate analysis showed that AMC, BVI, and T were significant independent factors for RFS or OS. Moreover, the combination of AMC/BVI was an especially significant factor for RFS or OS (P < 0.0001, P = 0.0003, respectively). When stratified by T, a significant impact of AMC or BVI on RFS was seen in patients with T1, T2, and T3 carcinomas. Multivariate analysis in patients with T2 carcinoma showed that both AMC and BVI were significant independent factors for RFS (P = 0.0231, P = 0.0388, respectively) and OS (P = 0.0331 and P = 0.0479, respectively). AMC, BVI, and T were independent prognostic indicators. As the combined impact of AMC/BVI is especially strong, AMC/BVI is useful in selecting high-risk node-negative breast cancer patients who may be eligible to receive aggressive adjuvant chemotherapy.

Adolescent↗

The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators.

OBJECTIVE: We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for mucous membrane pemphigoid. PARTICIPANTS: Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of mucous membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. EVIDENCE: The first author (L.S.C.) conducted a literature search. Based on the information obtained, international experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for mucous membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. CONSENSUS PROCESS: A consensus meeting was convened and conducted on May 10, 1999, in Chicago, Ill, to discuss the relevant issues. The first author drafted the statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. CONCLUSIONS: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection.

Humans↗

Perfusion lung scan as a prognostic indicator of response to beraprost sodium in idiopathic pulmonary arterial hypertension.

STUDY OBJECTIVE: To study whether there is any difference in the clinical characteristics between the two patterns of perfusion lung scan of idiopathic pulmonary arterial hypertension (normal vs. diffuse, multiple ill-defined defects) and whether the perfusion lung scan patterns of these patients would predict the effect of long-term use of beraprost sodium. METHODS: We evaluated 27 patients who used beraprost sodium for over 3 months, and noted a diffuse patchy pattern in 13 cases and a normal pattern in the remaining 14 cases. We judged that beraprost sodium was effective when at least two of the following conditions were met: improvement in symptom of dyspnea, more than 10% decrease in peak velocity of tricuspid valve regurgitation by echocardiography (Vmax), or more than 10% increase in 6-min walking distance. RESULTS: At baseline there was no difference between the two groups in dyspnea, hemodynamic parameters, and 6-min walking distance. After the use of beraprost sodium, the normal group showed improvement in dyspnea, 6-min walking distance, and Vmax. But the diffuse patchy group showed no improvement. The use of beraprost sodium in the normal group was effective in 10 out of 14 cases, but was effective in only two out of 13 cases in the diffuse patchy group. CONCLUSION: Perfusion lung scan pattern in patients with idiopathic pulmonary arterial hypertension is a useful prognostic indicator of the response to beraprost sodium.

Adolescent↗

Vestibular diagnosis as prognostic indicator in sudden hearing loss with vertigo.

The majority of episodes of sudden hearing loss are caused by inner ear disorders, often accompanied by vertigo. The patterns of hearing loss usually influence the prognosis. The purpose of this study was to analyze vestibular diagnoses in sudden hearing loss with vertigo, and to correlate them with the recovery of hearing loss. The clinical records of 125 patients with sudden hearing loss were reviewed. Various vestibular evaluations were performed in 36 patients with vertigo. The vertigo in these patients was classified as normal, unilateral hypofunction, directional preponderance, benign paroxysmal positional vertigo (BPPV), non-specific or irritative. The initial and final pure-tone audiograms of these patients were compared. The distribution of vestibular diagnoses was unilateral hypofunction in 30.6% of patients, BPPV in 25.7%, normal in 19.4%, non-specific in 11.1%, directional preponderance in 8.3% and irritative in 8.3%. The recovery of hearing in patients with vertigo was significantly worse than in those without vertigo. The recovery of hearing in patients with spinning vertigo did not differ from that of patients with non-spinning vertigo. The recovery of hearing was worst in the BPPV group, especially in the high frequency range, followed by the unilateral hypofunction group, who showed hearing thresholds between those in the BPPV group and those in the normal vestibular function test group. This study suggests that the diagnostic classification of vestibulopathy is a useful prognostic indicator of hearing recovery in sudden hearing loss with vertigo. We conclude that otolithic and semicircular canal involvement may cause poor hearing results, especially in the high frequency range.

Adult↗

Baseline radiographic defect angle of the intrabony defect as a prognostic indicator in regenerative periodontal surgery with enamel matrix derivative.

INTRODUCTION: The baseline radiographic defect angle has previously been correlated with the clinical outcomes of intrabony defects treated with access flap or guided tissue regeneration. The aim of this study was to investigate whether an association exists between baseline radiographic defect angle and treatment outcome when enamel matrix derivative (EMD) is used in periodontal regenerative surgery. MATERIALS AND METHODS: Baseline radiographs were collected from the test group of a previously published clinical trial using a population of 166 patients treated for chronic periodontitis. All intrabony defects were > or =3 mm for inclusion in the original study. Either modified or simplified papilla preservation technique was used to access the defect. The roots were conditioned with an EDTA gel and the primary outcome measure was clinical attachment level (CAL) change, 1 year after surgery. RESULTS: Sixty-seven radiographs were measurable. The probability of obtaining CAL gain >3 mm was 2.46 times higher (95% confidence interval: 1.017-5.970) when the radiographic defect angle was < or =22 degrees than when it was > or =36 degrees. CONCLUSIONS: This study showed that there was a significant association between baseline radiographic defect angle and CAL gain at 1 year. The observed increased odds ratio of obtaining CAL gain of > or =4 mm after regenerative surgery with EMD is used in narrow (< or =22 degrees ) intrabony defects, suggests that the baseline radiographic defect angle might be used as a prognostic indicator of treatment outcome.

Adult↗

The membrane-anchored matrix metalloproteinase (MMP) regulator RECK in combination with MMP-9 serves as an informative prognostic indicator for colorectal cancer.

PURPOSE: RECK, a membrane-anchored regulator of matrix metalloproteinases (MMPs), is widely expressed in healthy tissue, whereas it is expressed at lower levels in many tumor-derived cell lines. Studies in mice and cultured cells have shown that restoration of RECK expression inhibits tumor invasion, metastasis, and angiogenesis. However, the clinical relevance of these findings remains to be fully documented. Here we examined the expression of RECK and one of its targets, MMP-9, in colorectal cancer tissue. EXPERIMENTAL DESIGN: The RECK and MMP-9 expression levels in colorectal cancer samples from 53 patients were determined by immunohistochemical techniques. The expression level of each protein was scored, and the patients were divided into two groups based on these scores. In 33 cases, we performed gelatin zymography to estimate the degree of MMP-2 and MMP-9 activation. Microvessel density and vascular endothelial growth factor (VEGF) expression were also evaluated histologically. RESULTS: RECK protein was detected in 30 of 53 (56.6%) specimens. Importantly, patients with tumors expressing relatively high levels of RECK (high-RECK group) had a significantly lower risk of recurrence than did patients with tumors expressing relatively low levels of RECK (low-RECK group; P = 0.011). Moreover, RECK-dominant (RECK score > or = MMP-9 score) patients showed a significantly lower incidence of recurrence than did MMP-9-dominant patients (P = 0.0003). Multivariate analysis revealed that the RECK/MMP-9 balance was an independent prognostic factor (P = 0.0122). The expression of VEGF and microvessel density were inversely correlated with the level of RECK expression. CONCLUSIONS: RECK/MMP-9-balance is an informative prognostic indicator for colorectal cancer. Our data also suggest that RECK suppresses tumor angiogenesis, probably by limiting the availability of VEGF in tumor tissues.

Aged↗

mRNA expression of target genes in the urinary sediment as a noninvasive prognostic indicator of CKD.

BACKGROUND: Study of messenger RNA (mRNA) expression of target genes in urinary sediment was suggested as a noninvasive marker of renal damage in patients with chronic kidney diseases (CKDs). We studied the relationship between urinary mRNA expression of target genes and risk for renal function deterioration in patients with CKD. METHODS: We studied 131 patients with CKD with kidney biopsy. mRNA expression of 11 target genes in urinary sediment was measured by means of quantitative polymerase chain reaction. Patients then were followed up for 27.4 +/- 10.1 months. The primary end point is doubling of serum creatinine concentration or end-stage renal disease. RESULTS: Thirty-six patients (27.5%) reached the primary end point during follow-up. Univariate analysis showed that sex, age, proteinuria, estimated glomerular filtration rate, histological diagnosis, degree of tubulointerstitial scarring, percentage of glomerulosclerosis, and urinary mRNA expression of hepatocyte growth factor (HGF) were predictors of the primary end point. At 24 months, event-free survival rates were 90.9% and 64.3% for patients with low and high urinary HGF expression, respectively (log rank test, P = 0.002). After adjusting for other confounding factors by using a Cox proportional hazard model, urinary HGF expression remained an independent predictor of the primary end point, and a 1-fold increase in expression was associated with a 4.0% (95% confidence interval, 0.5 to 7.5; P = 0.024) increase in risk. CONCLUSION: In the target genes examined, urinary HGF expression is an independent prognostic indicator of CKD after adjusting for confounding clinical and histological factors. Measurement of urinary HGF mRNA expression may be a useful noninvasive tool for risk stratification of patients with CKD.

Biopsy↗

Previous tonsillectomy as prognostic indicator for success of uvulopalatopharyngoplasty.

Factors that determine a successful outcome following uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA) are not well defined. This study was undertaken to determine if prior tonsillectomy is predictive of a lower response rate to UPPP. A retrospective review of a cohort undergoing UPPP alone or in combination with nasal septoplasty for OSA was undertaken. Preoperative and postoperative polysomnograms were obtained to evaluate the severity of the OSA. The sample was a consecutive series of 79 patients with OSA. Clinical evaluation was performed by both an otolaryngologist and a pulmonologist. Surgical treatment in this group of 79 patients included 52 UPPP and 27 UPPP in patients with prior tonsillectomy. Concurrent septoplasty was undertaken in 17 patients. Criteria for outcome were based on comparison of preoperative and postoperative polysomnograms (i.e., apnea index, respiratory disturbance index change, and lowest saturation). A response to therapy was defined as a reduction in apnea index greater than 50%. A success was defined as apnea index less than 5, reduction of respiratory disturbance index greater than 50%, and nadir saturation greater than 82%. In 79 patients with OSA, 78% responded and 37% reflected therapeutic successes. Patients with history of prior tonsillectomy were less likely to have therapeutic improvement following UPPP. In 52 patients without previous tonsillectomy, 88% responded and 52% had a successful outcome. Of those with previous tonsillectomy, 59% responded and 7% had a successful outcome. The status of previous tonsillectomy is an important prognostic indicator in the success of UPPP for the treatment of OSA. We speculate that the presence of palatine tonsils allows the removal of an extra measure of oropharyngeal tissue, thereby improving the likelihood of success for UPPP.

Adult↗

Associations between insulin-like growth factors and their binding proteins and other prognostic indicators in breast cancer.

Recent studies have suggested that insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) may be implicated in the development and progression of breast cancer. Prostate-specific antigen (PSA), a serine protease, may play a role in the regulation of IGFs' function through cleavage of IGFBP-3, resulting in release of active IGFs from IGFBP-3. As IGFs, IGFBPs and PSA are all present in breast cancer, possible associations among these proteins were speculated. In this study, we have measured PSA, IGF-I, IGF-II, IGFBP-1 and IGFBP-3 in tumour tissue cytosols from 200 women with primary breast cancer, and have examined relationships between IGFs or IGFBPs and PSA along with other markers, including p53 protein, steroid hormone receptors (oestrogen and progesterone), cathepsin-D, epidermal growth factor receptor, Her-2/neu protein, S-phase fraction and DNA ploidy. Correlations or associations between PSA and IGF-I, IGF-II, IGFBP-1 or IGFBP-3 were not observed. IGF-II was positively correlated with both IGFBP-3 and IGFBP-1. IGF-I was not associated with either of the two binding proteins, nor with IGF-II. Both IGF-II and IGFBP-3 were inversely associated with the oestrogen receptor, and IGFBP-3 was also positively associated with S-phase fraction. Our finding of IGF-II and IGFBP-3 in association with unfavourable prognostic indicators of breast cancer suggests that IGFs may be involved in the progression of breast cancer.

Biomarkers, Tumor↗

Reduction of p12DOC-1 expression is a negative prognostic indicator in patients with surgically resected oral squamous cell carcinoma.

PURPOSE: p12DOC-1 is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. Expression of p12DOC-1 is reduced and/or lost in tumor tissues. The purpose of this study is to correlate in vivo the expression of p12DOC-1 in oral cancer tissues by immunohistochemistry with clinical and pathological parameters. EXPERIMENTAL DESIGN: Twenty-five cases of normal oral mucosa and 127 cases of oral squamous cell carcinomas were evaluated. Patients' charts were reviewed for clinical, pathological, and 10-year survival data. Because p12DOC-1 is a growth suppressor and associates with CDK2, parallel immunostaining was done for proliferating cell nuclear antigen and CDK2 to evaluate cell proliferation and potential correlation with CDK2. RESULTS: Our results showed that strong p12DOC-1 staining was uniformly seen in normal oral mucosa. p12DOC-1 staining was reduced or absent in 81 cases (63.8%) of oral squamous cell carcinomas. Decreased p12DOC-1 staining (<25% of cells stained) correlated with tumor mode of invasion (P = 0.001) and higher proliferating cell nuclear antigen (P = 0.0028) and CDK2 (P = 0.0020) expression. Survival analysis showed significant correlation of low p12DOC-1 expression with the risk of cervical lymph node metastasis (P = 0.001) and patients' 10-year survival status (P = 0.0214). CONCLUSIONS: These results allow us to conclude that reduction of p12DOC-1 protein expression is a frequent event in oral cancers. Intratumor immunohistochemical evaluation of p12DOC-1 expression can be an adjunctive prognostic indicator for patients with oral cancer.

Adult↗

Prognostic indicators of survival in advanced endometrial cancer.

Advanced endometrial cancer represents 14% of all stages but 54% of all deaths attributed to endometrial cancer. From 1973 to 1990, the charts of 137 patients with endometrial cancer (Stage III and IV) treated by the section of Gynecologic Oncology at Rush Medical College were retrospectively reviewed. The log rank method was used for univariate analysis and Cox proportional hazards regression was used for multivariate analysis. The patients were stratified as follows: Stage III, 92 (67.2%), Stage IV, 45 (32.8%); Grade 1, 15 (10.9%), Grade 2, 47 (34.3%), Grade 3, 67 (48.9%); adenocarcinoma, 93 (67.9%), adenosquamous, 18 (13.1%), adenoacanthoma, 2 (1.5%), clear cell, 1 (0.7%), papillary serous, 23 (16.8%). Using univariate analysis, median survival was 1.71 years for Stage III versus 0.68 years for Stage IV. Median survival based on treatment was as follows: radiotherapy (RT) only (n = 16), 0.89 years, surgery only (n = 36), 0.75 years, preoperative RT+surgery (n = 7), 2.5 years, surgery+postoperative RT (n = 56), 2.63 years, and other treatments (hormonal only n = 12, chemotherapy only n = 1, and no treatment n = 9), 0.6 years. Patients with vaginal extension survived a median of 0.82 years, versus 2.49 years without this factor (P = 0.002). Patients with clinically apparent parametrial involvement survived a median of 0.70 years versus 2.65 years without this factor (P = 0.0003). Multivariate analysis was possible via a surgical database (n = 99). Age > 60 (P = 0.01), parametrial involvement (P = 0.04), and abdominal metastases (P = 0.003) were significant prognostic indicators. Papillary or clear cell histology, advanced grade, and mode of treatment were not significant. Patients with abdominal metastases or parametrial extension of tumor have a significant decrease in mean survival.

Age Factors↗

Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival.

Malignant melanomas of the skin are distinguished by their propensity for early metastatic spread via lymphatic vessels to regional lymph nodes, and lymph node metastasis is a major determinant for the staging and clinical management of melanoma. However, the importance of tumor-induced lymphangiogenesis for lymphatic melanoma spread has remained unclear. We investigated whether tumor lymphangiogenesis occurs in human malignant melanomas of the skin and whether the extent of tumor lymphangiogenesis may be related to the risk for lymph node metastasis and to patient survival, using double immunostains for the novel lymphatic endothelial marker LYVE-1 and for the panvascular marker CD31. Tumor samples were obtained from clinically and histologically closely matched cases of primary melanomas with early lymph node metastasis (n = 18) and from nonmetastatic melanomas (n = 19). Hot spots of proliferating intratumoral and peritumoral lymphatic vessels were detected in a large number of melanomas. The incidence of intratumoral lymphatics was significantly higher in metastatic melanomas and correlated with poor disease-free survival. Metastatic melanomas had significantly more and larger tumor-associated lymphatic vessels, and a relative lymphatic vessel area of >1.5% was significantly associated with poor disease-free and overall survival. In contrast, no differences in the density of tumor-associated blood vessels were found. Vascular endothelial growth factor and vascular endothelial growth factor-C expression was equally detected in a minority of cases in both groups. Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in cutaneous melanoma.

Adult↗

Clinical and demographic prognostic indicators for human disc cell proliferation in vitro: pilot study.

STUDY DESIGN: Human anulus cells were cultured under control and experimental conditions to study associations between proliferation and clinical-demographic features of subjects from which cells were obtained. Statistical multiple regression analyses were applied to develop mathematic models relating proliferation to age, gender, Thompson score (denoting stage of disc degeneration), and status (control donor [postmortem]; surgical patient). OBJECTIVES: To identify the effect of donor characteristics on proliferative capacities of human disc cells. SUMMARY OF BACKGROUND DATA: As therapeutic options for disc degeneration increase, novel biologic options are important future considerations. Little is known about the influence of clinical-demographic features on cell proliferation. METHODS: Anulus cells were studied in two designs: 1) Cells from 12 individuals were grown in monolayer with 50 ng/mL interleukin growth factor-1 (IGF-I), 100 ng/mL insulin, or control conditions. 2) Cells from nine individuals were grown in three-dimensional culture with 10 ng/mL IGF-I or control conditions. Cell proliferation data and data on age, gender, Thompson score, and status were collected. Standard statistical analyses were used to develop correlation models. RESULTS: Data from monolayer experiments produced significant models fitting proliferation in the presence of low serum, 50 ng/mL IGF-I, or insulin, with age, gender, Thompson score, and status (respective R2: 0.827, 0.680, 0.850). Three-dimensional cultures exposed to 10 ng/mL IGF-I resulted in proliferation that correlated in a significant negative manner with Thompson score (r = -0.798). CONCLUSIONS: Clinical-demographic prognostic indicators may help predict levels of proliferation. Greater age, greater disc degeneration, female gender, and surgical derivation had deleterious effects on proliferation potential in this model.

Adolescent↗

Neutralizing antibodies as a prognostic indicator in the progression of acquired immune deficiency syndrome (AIDS)-related disorders: a double-blind study.

A double-blind longitudinal study for the presence of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies (NAb) in the sera of 36 patients with acquired immune deficiency syndrome (AIDS), 149 prodromal homosexual subjects, and 33 heterosexual subjects has been carried out. All AIDS patients and 68% of prodromal homosexual subjects (101/149) were found to be HIV-1 antibody positive by Western blot assay. All heterosexual subjects were HIV-1 antibody negative. Neutralizing antibody(s) was determined by testing the protective activity of sera against HIV-1 infection of human T-cell line H9. Study subjects were divided into NAb(+) (antibody titer, greater than 1:40) and NAb(-) (antibody titer, less than 1:40) groups. During the 24-month observation period 2 of 80 (3%) HIV-1(+) NAb(+) individuals progressed to AIDS and died, as compared to 5 of 21 (24%) of HIV-1(+) NAb(-) subjects who progressed to AIDS. Similarly, among the NAb(+) AIDS patients 8 of 23 (35%) died, while 10 of 13 (77%) of the NAb(-) patients died during the course of the study. In addition, the absence or reduction of HIV-1 p17 and p24 antibodies directed against HIV-1 antigens as well as the low titer or absence of NAb appears to be closely related to the clinical progression of the disease. These studies suggest that a decrease in the virus neutralization capacity of the sera and a decrease or complete loss of HIV-1 p17 and p24 antibodies may be useful as prognostic indicators for the progression of disease in HIV-1-seropositive patients.

AIDS-Related Complex↗