The role of serum laminin P1 in the diagnosis of transitional cell carcinoma of the bladder.

In order to explore the possible role of serum laminin P1 in the diagnosis of transitional cell carcinoma (Tcc) of the bladder, the sera of 50 healthy control subjects and of 35 bladder-cancerous patients were measured by radioimmunoassay. In 27 patients (77%), the serum level was elevated above the upper limit of normal range. Statistically significant elevation could be determined in all stages and grades of Tcc of the bladder compared to those of normal subjects (mean +/- SD: 1.18 +/- 0.16 kU/l). Deterioration of the clinical stages or pathologic grades of the tumor was associated with a progressive increase in the mean values of serum laminin P1. A longer study with serial determination is planned to assess the prognostic significance of serum laminin in bladder cancer patients.     

Use of carcinoembryonic antigen in small cell lung cancer. Prognostic value and relation to the clinical course 1

Carcinoembryonic antigen (CEA) was measured in 147 patients at diagnosis of small cell lung cancer; 17% of patients with limited disease and 51% with extensive disease had an abnormal CEA level (greater than 10 ng/ml). The median level was higher in extensive than in limited disease (11 ng/ml and 5.8 ng/ml, respectively; P less than 0.001). Multivariate analysis showed CEA level greater than or equal to 50 ng/ml to be an adverse prognostic factor (P = 0.02); median survival at this level was shorter than at less than 50 ng/ml (7 and 46 weeks, respectively; P = 0.002). No consistent directional changes of follow-up CEA values were observed in patients with initially normal CEA levels, but normalization of levels occurred in complete responders. We recommend that CEA be measured in this disease at diagnosis as an additional prognostic factor and that patients with abnormal initial CEA levels have follow-up measurements to aid in evaluating response.     

Duplex ultrasonography rarely changes management decisions in chronic lower extremity ischemia

The purpose of this study was to determine the proportion of patients presenting with lower extremity pain whose treatment plan was altered by duplex ultrasonography. This prospective study evaluated all patients referred for lower extremity pain who had undergone a lower extremity arterial duplex scan. All patients underwent a history and physical examination by the same vascular surgeon. After the completion of the history and physical examination, the surgeon established a preliminary treatment plan. Subsequently, he reviewed the lower extremity duplex results and established a final treatment plan based on the history, physical examination, and duplex results. Treatment was labeled as either (1) conservative, (2) aggressive, or (3) the patient was considered to have no peripheral vascular disease. The proportion of patients whose primary treatment plan was altered by the addition of duplex ultrasonography was determined. Of 103 patients who entered the study, 7% had no peripheral vascular disease based on the history, physical examination, and duplex scan. Based on the history and physical examination alone, 48.5% were to be treated conservatively and 44.7% aggressively. After reviewing duplex results, the treatment plan was changed in only 5.9% of patients. There was no difference in treatment plan after the addition of the duplex results (p = 0.1025). Duplex ultrasonography remains a valuable tool in the evaluation of patients with lower extremity peripheral vascular disease; however, in most patients, the decision to treat conservatively or aggressively can be made without duplex scanning. All patients referred to the vascular clinic for lower extremity evaluation do not require a duplex scan.     

Management of sensitized patients awaiting renal transplantation: does sequential therapy of intravenous immunoglobulin and simvastatin offer a solution?

The value of intravenous immunoglobulin and simvastatin as potential modalities for the treatment of sensitized patients was studied. We aimed to test their efficacy as solo agents to inhibit anti-human leukocyte antigen (HLA) antibodies. We tested samples from 11 adult hemodialysis patients who were waiting for renal allotransplantation at our center, all of whom had persistently positive crossmatches with their living related donors and panel reactive antibody titers more than 20%. All patients received intravenous immunoglobulin (500 mg/kg/day on alternate days for 6 doses). Panel reactive antibody titer measurement and crossmatch testing were carried out after each dose and before each subsequent one. Two months later, 8 patients received simvastatin (20 mg/day) for 2 months. Panel reactive antibody measurement titer and crossmatch testing were carried out every 2 weeks. Only 4 patients showed an insignificant reduction in panel reactive antibody activity (P=0.36). None of them attained a negative crossmatch. Furthermore, simvastatin also resulted in an insignificant reduction of HLA antibodies in 3 patients (P=0.32). We concluded that intravenous immunoglobulin or simvastatin alone cannot effectively inhibit preformed anti-HLA antibodies to allow successful renal transplantation. Further trials of the use of intravenous immunoglobulin and simvastatin with other modalities to desensitize these patients may be warranted.     

Impact of CD31 mismatches on the outcome of hematopoeitic stem cell transplant of HLA-identical sibling

Graft-versus host disease (GVHD) complicating allogeneic hematopoeitic stem cell transplantation (HSCT) is often attributed to mismatching of minor histocompatibility antigens (mHags), which are poorly defined in humans. CD31 is a candidate human mHag relevant to acute GVHD (aGVHD), but reports disagree about its level of significance. Therefore, we examined the impact of CD31-matching on the outcome of HSCT in different hematological and immunological diseases. About 60 patients receiving HSC from their respective HLA-ABCDR and DQ-identical sibling were studied. DNA was used to study the CD31 allele polymorphism at the codon 125 (LL, LV or VV) in the patient-donor pairs using the principle of allele-specific PCR amplification. Four primer were used; two primers (forward and reverse) for the L allele and another two for the V allele. The CD31 identity was tested for correlation with HSCT outcome measures of aGVHD, chronic GVHD, and relapse. The gene frequency of CD31 alleles (LL, VV and LV) was 28.3, 20 and 51.7%, respectively. CD31 identity was found in 31 pairs (51.7%) versus 29 pairs (48.3%) for nonidentity. The CD31 noncompatibility showed statistical non-significant relation with aGVHD (G 0-I, and G II-IV) and chronic GVHD (De-novo and chronic on acute) (p = 0.59, p = 0.62, p = 036 and p = 0.83, respectively). The CD31 nonidentity had statistical significant relation with aGVHD versus no aGVHD (p = 0.008 and OR = 4.46). The CD31 nonidentity showed statistical significant relation with aGVHD (II-IV) versus no aGVHD (p = 0.012 and OR = 7.14) and also, aGVHD (0-I) versus the no aGVHD (p = 0.03, OR = 3.13, respectively). A statistical significant relation was found between CD31 nonidentity in patient-donor pairs and relapse (p = 0.014 and OR = 4.21). In conclusion, the donor-recipient CD31 nonidentity is a significant risk factor for aGVHD and relapse in HLA-identical sibling.     

HLA alleles in frequently relapsing steroid-dependent and -resistant nephrotic syndrome in Egyptian children

The association between HLA class II antigens and childhood primary nephrotic syndrome has been reported in different populations. To investigate this association in Egyptian children, DRB1 alleles were typed by DNA polymerase chain reverse hybridization in 20 frequent relapsers/steroid-dependent and 14 steroid-resistant children with minimal change nephrotic syndrome (MCNS) and 121 unrelated healthy controls from the northern part of Egypt. The strength of the association was expressed as the relative risk (RR) estimated by the odds ratio. The DRBI *07011 allele frequency was significantly higher among patients than controls (78.9% vs. 16%, Pc <0.001). The etiological fraction (EF) was high at 0.75 [RR=20.1, confidence interval (CI)=6.0–66.7]. Similarly, patients with steroid-resistant MCNS had a higher frequency of the DRBI *07011 allele than controls (64.3% vs. 16.5%, P c<0.001). The EF was high at 0.57 (RR=9.6, CI 2.9–31.7). In the whole group of patients the frequency of DRBI *11 alleles was low compared with controls (11.4% vs. 32.2%, P =0.02), but was not significant when P was corrected. In conclusion, the DRBI *07011 allele confers susceptibility to a frequently relapsing and steroid-dependent or steroid-resistant course of childhood MCNS. These patterns of the disease seem to have the same immunogenetic components.     

Women age < or = 35 years with primary breast carcinoma: disease features at presentation

BACKGROUND: The purpose of the current study was to describe a population of young patients with breast carcinoma, their characteristics at the time of diagnosis, and the association of these characteristics with disease recurrence and survival. METHODS: Four hundred fifty-two women age < or = 35 years with breast carcinoma were registered at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between 1990 and 2002. The relation between clinicopathologic factors and disease recurrence-free survival (RFS) and overall survival (OS) was assessed. Cox regression analysis was used to identify independent survival predictors. RESULTS: The median age of the patients was 32 years. Most of the patients were white, and 20% were obese. Approximately 50% reported oral contraceptive use, 34% reported a family history of breast carcinoma, and 5% reported a family history of ovarian carcinoma. Sixty-nine percent of tumors were nuclear Grade 3 (using the modified Black's nuclear grading system), 52% had positive estrogen receptors, and 48% had positive progesterone receptors. HER-2/neu status was available in 60% of tumor specimens and 34% were HER-2/neu positive. The median follow-up was 36 months. There were 185 disease recurrences and 84 deaths. RFS was significantly shorter in patients who reported a family history of ovarian carcinoma (P < 0.0001) and in those who had hormone receptor-negative tumor specimens (P = 0.001). OS was significantly shorter in patients who reported a family history of ovarian carcinoma (P = 0.001), those who had hormone receptor-negative tumor specimens (P < 0.0001), or those with > nuclear Grade 3 tumor specimens (P = 0.005). CONCLUSIONS: This young population with breast carcinoma was found to have more aggressive biologic features. Hormone receptor negativity and a family history of ovarian carcinoma were associated with shorter RFS and OS.     

Pretransplant mixed lymphocyte culture still has an impact on graft survival

BACKGROUND/AIM: Mixed lymphocyte culture (MLC) is an important in vitro test for studying allograft reaction. The recipient-donor MLC reflects donor specific hypo- or hyperimmune response. The various studies have been correlated donor-specific MLC reactivity with graft survival in cadaver kidney transplantation. This retrospective study reports the relationship between of MLC hyper-responsiveness and graft survival in living-donor kidney transplantation. METHODS: The study included 477 patients who underwent live-donor kidney transplantation between Marsh 1976 and January 2002. They were divided according to the relative response (RR) of pre transplant one way MLC into hypo responders (RR <4) and hyper responders (RR >4). The demographic and follow-up data for both groups were recorded. The duration of follow-up ranged from 44 to 84 months. RESULTS: The two groups were homogeneous regarding age, sex, donor source, HLA-A, B-and -DR mismatches, number of blood transfusion and type of 3 primary immunosuppressions. Acute rejection (AR) episodes were seen in 182 (44.8%) patients in the hypo-responders group, of whom 10 were steroid resistant, while in the hyper-responder recipients, AR episodes occurred in 33 patients (46.5%) of whom 5 patients (15.2%) were steroid resistant (p < 0.05). Chronic allograft nephropathy occurred in 14.5% and 27.3% and the actuarial 5-year graft survival was 79% and 60% (p = 0.03).in the hypo- and hyper-responder groups, respectively. CONCLUSIONS: It is concluded that MLC reaction may predict high-risk patients for immunological graft failure and that more potent immunosuppression should be considered in MLC hyper-responders.     

Familial Transmissability of Early Age at Initial Diagnosis in Coronary Heart Disease (CHD): Males Only, and Mediated by Psychosocial/Emotional Distress?

In equal sized samples, a strong association between a positive Family History of Early Coronary Heart Disease (FamHx) and early Age at Initial Diagnosis (AAID) was found only for males, and thus all further analyses were restricted to males. All three scales of the self-report version of the Ketterer Stress Symptom Frequency Checklist--Revised (KSSFCR)--"AIAI" (or aggravation, irritation, anger, and impatience), Depression, and Anxiety--were associated with both a positive FamHx and early AAID. A series of regression models was used to demonstrate that the KSSFCR scales may plausibly account for 22-32% of the variance in the relationship between a positive FamHx and early AAID. Because of previously documented denial in males, the analyses were repeated in a subgroup of males for whom Spouse/Friend KSSFCRs were obtained. Spouse/Friend-reported AIAI was related to both early FamHx and early AAID, and could account for 68% of the common variance.