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Biomedical subjects

J Rubio

Publications and source records attributed to J Rubio.

At least 19 recordsLinked to original sources

Association of the CT gene (CA) polymorphism with BMD in osteoporotic Mexican women.

Calcitonin (CT) plays a role in the pathogenesis of osteoporosis and genetic variations in or adjacent to the CT gene may be associated with loss of bone mineral density (BMD). The correlation between a dinucleotide (cytosine-adenine) repeat polymorphism at the CT locus and BMD was examined in 70 osteoporotic women, 70 non-osteoporotic women and 500 subjects from the Mexican population. The allele A and genotype AA frequencies were significantly higher in osteoporotic women than in non-osteoporotic women (60% vs 32%; p < 0.0001 and 41% vs 14%; p = 0.0007, respectively). Genotype AA was associated with the presence of osteoporosis [odds ratio 2.58; 95% confidence interval (CI); 1.62-4.12]. Likewise, the loss of lumbar BMD and T scores were related to the presence of allele A: subjects with a single A allele displayed lower values for lumbar BMD and T score (84.02% and -1.51, respectively) than those who do not present any A allele (89.61% and -0.88, respectively). Individuals with two alleles A showed the lowest lumbar BMD and T-score values (73.77% and -2.51, respectively). Analysis of potential confounder demonstrated that aging has a significant effect on osteoporosis development (odds ratio 1.1; 95% CI; 1.1052-1.152).

Adult↗

High thoracic epidural blockade increases myocardial oxygen availability in coronary surgery patients.

BACKGROUND: High thoracic epidural techniques are increasingly being used in patients scheduled for cardiothoracic surgery, including coronary artery bypass grafting. In the present study, we evaluated the acute effects of the epidural blockade on myocardial oxygen availability by means of tissue oxygen pressure monitoring in patients submitted for surgical revascularization. METHODS: Fifty adult patients were included in a prospective, randomized, double-blind study. After placement of an epidural catheter in thoracic space T1-T2, and under general anesthesia, 5-10 ml of either normal saline or 0.3% ropivacaine was injected through the epidural catheter. Hemodynamic parameters and the intramyocardial oxygen partial pressure were recorded before and 20 min after the epidural injection. RESULTS: There were no demographic or hemodynamic differences between the groups before intervention. A significant increase in intramyocardial partial oxygen pressure was observed in the ropivacaine group (14.6 mmHg vs. 25.1 mmHg, P < 0.0005). CONCLUSION: High thoracic epidural blockade with 5-10 ml of 0.3% ropivacaine increases myocardial oxygen availability in coronary diseased patients prior to surgical revascularization without deleterious hemodynamic disturbances.

Aged↗

Effect of Black maca (Lepidium meyenii) on one spermatogenic cycle in rats.

Lepidium meyenii (Maca) grows exclusively between 4000 and 4500 m above sea level in the Peruvian central Andes. The hypocotyls of this plant are traditionally used in the Andean region for their supposed fertility-enhancing properties. The hypocotyls have different colours. Of these, Black maca has better effects on spermatogenesis. The present study aimed to test the hypothesis that Black maca has early effects during a spermatogenic cycle (12 days) of male rats. For this, testicular spermatid, epididymal sperm and vas deferens sperm counts were measured after 1, 3, 5, 7 and 12 days of treatment with Black maca. Aqueous extract of Black maca was given orally by daily gavage at a dose of 2 g kg(-1). In a spermatogenic cycle, compared with day 1, daily sperm production (DSP) was lower at day 7 (control), whereas with Black maca, the difference was observed at day 12. Epididymal sperm count was higher in rats treated with Black maca at days 1, 3 and 7, but similar to controls at days 5 and 12; similarly sperm counts in vas deferens was higher in rats treated with Black maca in days 3, 5 and 7, but similar to controls at days 1 and 12. From this, it is suggested that first action of Black maca was at epididymal level increasing sperm count after 1 day of treatment, whereas an increase in sperm count was observed in vas deferens at day 3 of treatment. Finally, an increase in DSP was observed after 7 days of treatment with Black maca. Testicular testosterone was not affected after 7 days treatment with Black maca. In conclusion, Black maca affects sperm count as early as 1 day after beginning of treatment.

Animals↗

Detection of two quantitative trait loci for resistance to ascochyta blight in an intra-specific cross of chickpea (Cicer arietinum L.): development of SCAR markers associated with resistance.

Two quantitative trait loci (QTLs), (QTL(AR1) and QTL(AR2)) associated with resistance to ascochyta blight, caused by Ascochyta rabiei, have been identified in a recombinant inbred line population derived from a cross of kabulixdesi chickpea. The population was evaluated in two cropping seasons under field conditions and the QTLs were found to be located in two different linkage groups (LG4a and LG4b). LG4b was saturated with RAPD markers and four of them associated with resistance were sequenced to give sequence characterized amplified regions (SCARs) that segregated with QTL(AR2). This QTL explained 21% of the total phenotypic variation. However, QTL(AR1), located in LG4a, explained around 34% of the total phenotypic variation in reaction to ascochyta blight when scored in the second cropping season. This LG4a region only includes a few markers, the flower colour locus (B/b), STMS GAA47, a RAPD marker and an inter-simple-sequence-repeat and corresponds with a previously reported QTL. From the four SCARs tagging QTL(AR2), SCAR (SCY17(590)) was co-dominant, and the other three were dominant. All SCARs segregated in a 1:1 (presence:absence) ratio and the scoring co-segregated with their respective RAPD markers. QTL(AR2) on LG4b was mapped in a highly saturated genomic region covering a genetic distance of 0.8 cM with a cluster of nine markers (three SCARs, two sequence-tagged microsatellite sites (STMS) and four RAPDs). Two of the four SCARs showed significant alignment with genes or proteins related to disease resistance in other species and one of them (SCK13(603)) was sited in the highly saturated region linked to QTL(AR2). STMS TA72 and TA146 located in LG4b were described in previous maps where QTL for blight resistance were also localized in both inter and intraspecific crosses. These findings may improve the precision of molecular breeding for QTL(AR2) as they will allow the choice of as much polymorphism as possible in any population and could be the starting point for finding a candidate resistant gene for ascochyta blight resistance in chickpea.

Analysis of Variance↗

Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis.

Multiple sclerosis (MS) is an enigmatic disease of the central nervous system resulting in sclerotic plaques with the pathological hallmarks of demyelination and axonal damage, which can be directly or indirectly orchestrated by cells from the peripheral circulation. The majority of patients with MS follow a relapsing-remitting course in the early stages of the disease (RRMS) but most ultimately enter a secondary progressive phase (SPMS). About 10% of patients follow a primary progressive course from the onset (PPMS). We measured gene expression in whole blood of people with and without chronic progressive MS (CPMS), PPMS and SPMS, to discover genes which may be differentially expressed in peripheral blood in active disease, and so identify pathologically significant genes and pathways; and we investigated genetic differences in the promoters of dysregulated genes encoded in genomic regions associated with MS. If SPMS and PPMS were independently compared to the controls, there was little overlap in the set of most dysregulated genes. Ribosomal protein genes, whose expression is usually associated with cell proliferation and activation, were dramatically over-represented in the set of most down-regulated genes in PPMS compared to SPMS (P < 10(-4), chi(2)). The T cell proliferation gene IL7R (CD127) was also underexpressed in PPMS, but was up-regulated in SPMS compared to the controls. One interleukin 7 receptor (IL7R) promoter single nucleotide polymorphism (SNP), -504 C, was undertransmitted in PPMS trios (P = 0.05, TDT), and carriers of this allele were under-represented in PPMS cases from two independent patient cohorts (combined P = 0.006, FE). The four known IL7R promoter haplotypes were shown to have similar expression levels in healthy controls, but not in CPMS (P < 0.01, t test). These data support the hypothesis that PPMS has significant pathogenetic differences from SPMS, and that IL7R may be a useful therapeutic target in PPMS.

Down-Regulation↗

Immunohistochemical expression of Ki-67 antigen, cox-2 and Bax/Bcl-2 in prostate cancer; prognostic value in biopsies and radical prostatectomy specimens.

PURPOSES: To elucidate the prognostic value of the immunohistochemical (IHC) expression of Bcl-2, Bax, Cox-2 and Ki-67 antigen in biopsy cores (C) and surgical specimens (SP) of prostate cancer (PC) and to determine the C to SP reproducibility. MATERIAL AND METHODS: The IHC study was carried out in 91 patients operated by means of radical prostatectomy (RP) with available formalin-fixed paraffin-embedded material from both C and SP. RESULTS: The IHC expression of Bcl-2 in C and SP was very low (5%). Bax was expressed in almost all the patients and did not show any prognostic value. We observed a good reproducibility between C and SP for all molecules except with Bax. In prostate C, Ki-67 and Cox-2 were considered positive in 42.9% and 67% of the patients respectively, and were related to disease-free survival in the univariate analysis. The expression of these two markers in SP was observed in 51.6% and 79.1% of the patients and the expression of Ki-67 in SP maintained its independence as prognostic factor in the multivariate analysis related to disease-free survival. CONCLUSIONS: The IHC expression of Ki-67 and Cox-2 proteins in our study do offer valuable prognostic information, mostly the first one. Thus, we think these markers might be studied in larger series of patients for its further validation as prognostic factors in prostate biopsies.

Aged↗

Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.

BACKGROUND: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. METHODS: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. RESULTS: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. CONCLUSION: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Adult↗

A linkage map of chickpea (Cicer arietinum L.) based on populations from Kabuli x Desi crosses: location of genes for resistance to fusarium wilt race 0.

Two recombinant inbred line (RIL) populations derived from intraspecific crosses with a common parental line (JG62) were employed to develop a chickpea genetic map. Molecular markers, flower colour, double podding, seed coat thickness and resistance to fusarium wilt race 0 (FOC-0) were included in the study. Joint segregation analysis involved a total of 160 markers and 159 RILs. Ten linkage groups (LGs) were obtained that included morphological markers and 134 molecular markers (3 ISSRs, 13 STMSs and 118 RAPDs). Flower colour (B/b) and seed coat thickness (Tt/tt) appeared to be linked to STMS (GAA47). The single-/double-podding locus was located on LG9 jointly with two RAPD markers and STMS TA80. LG3 included a gene for resistance to FOC-0 (Foc0(1)/foc0(1)) flanked by RAPD marker OPJ20(600) and STMS marker TR59. The association of this LG with FOC-0 resistance was confirmed by QTL analysis in the CA2139 x JG62 RIL population where two genes were involved in the resistance reaction. The STMS markers enabled comparison of LGs with preceding maps.

Chromosome Mapping↗

Risk groups in patients with bladder cancer treated with radical cystectomy: statistical and clinical model improving homogeneity.

PURPOSE: In this study we identified homogeneous risk groups, with no survival overlap among the subgroups that make up each risk group, in patients with transitional cell carcinoma of the bladder treated with radical cystectomy alone. MATERIALS AND METHODS: Predictive factors for tumor death were analyzed with univariate and multivariate analysis among a group of 298 patients with transitional cell carcinoma of the bladder treated with radical cystectomy alone. Independent variables were progressively incorporated according to their statistical power in a stepwise process identifying a model with independent subgroups. The risk groups were identified according to different survival cutoff points including subgroups with similar survival. To search a clinical application and to check the strength of this model a new model was also set up using the weight score based on the size of hazard ratio from multivariate analysis. RESULTS: Univariate analysis demonstrated that lymphatic invasion status, pathological stage (P), lymph node status (N) and prostatic stroma status (St) were predictive variables for tumor death, and the latter 3 were independent variables in the multivariate analysis. By taking the most powerful, N, as the reference variable, and progressively incorporating additional variables, a model was found including 7 independent subgroups. In this model only 2 subgroups, N1 and N2-3, included more than 1 category and their survival was also calculated. Three risk groups were identified establishing different survival cutoffs. The 5-year cancer specific survival rate was 86.4% for low risk (P1-2N0St-), 64.4% (range 60.9% to 65.3%) for intermediate risk (P1-2N1St-, P3N0St-, HR = 2.7) and 28.1% (range 0% to 47.7%) for high risk (N2-3, P4, St+, N1P3, HR = 8.7). This model was also reproduced using the weight score based on the size of the hazard ratio from the multivariate analysis CONCLUSIONS: Three homogeneous risk groups were identified with high statistically significant survival differences among them and no survival overlap among subgroups that make up the risk groups.

Adult↗

Treatment of municipal wastewater UASB reactor effluent by unconventional flotation and UV disinfection.

Post-treatment of an UASB reactor effluent, fed with domestic sewage, was conducted using two-stage flotation and UV disinfection. Results were compared to those obtained in a parallel stabilisation pond. The first flotation stage employed 5 - 7.5 mg L(-1) cationic flocculant to separate off more than 99% of the suspended solids. Then, phosphate ions were completely recovered using carrier flotation with 5-25 mg L(-1) of Fe (FeCl3) at pH 6.3-7.0. This staged flotation led to high recoveries of water and allowed us to separate organic matter and phosphate bearing sludge. The water still contained about 1 x 10(2) NMP/100 mL total coliforms, which were removed using UV radiation to below detection levels. Final water turbidity was < 1.0 NTU, COD < 20 mg L(-1) O2 and 71 mNm(-1), the liquid/air interfacial tension. This flotation-UV flowsheet was found to be more efficient than the treatment in the stabilisation pond and appears to have some potential for water reuse. Results were discussed in terms of the biological, chemical and physicochemical mechanisms involved.

Ammonia↗

Effect of Lepidium meyenii (Maca) on spermatogenesis in male rats acutely exposed to high altitude (4340 m).

Lepidium meyenii (Maca) is a Peruvian hypocotyl that grows exclusively between 4000 and 4500 m in the central Andes. Maca is traditionally employed in the Andean region for its supposed fertility-enhancing properties. The aim of this study was to test the hypothesis that Maca can prevent high altitude-induced testicular disturbances. Adult male rats were exposed for 21 days to an altitude of 4340 m and treated with vehicle or aqueous extract of Maca (666.6 mg/day). The lengths of the stages of the seminiferous epithelium and epididymal sperm counts were obtained at 0, 7, 14 and 21 days of exposure. The stages of the seminiferous tubules were assessed by transillumination. A dose-response study was also performed at sea level to determine the effect of Maca given to male rats at doses of 0, 6.6, 66.6 and 666.6 mg/day for 7 days on body weight, seminiferous tubule stages and epididymal sperm count. The length of stage VIII and the epididymal sperm count were increased in a dose-dependent manner in Maca-treated rats but treatment reduced the length of stage I. At the highest dose, sperm count increased 1.58 times, the length of stage VIII increased 2.4 times and the length of stage I was reduced 0.48 times compared with the value at dose 0. Exposure to high altitude resulted in a reduction in epididymal sperm count after 7 days and lower values were maintained up to 21 days. Altitude reduced spermiation (stage VIII) to half and the onset of spermatogenesis (stages IX-XI) to a quarter on days 7 and 14 but treatment with Maca (666.6 mg/day) prevented these changes. Data on transillumination and epididymal sperm count in the Maca-treated group exposed to high altitude were similar to those obtained at sea level. Maca increased the sperm count on day 21 of exposure to high altitude to values similar (1095.25 +/- 20.41x10(6) sperm, means +/- S.E.M.) to those obtained in the Maca-treated group at sea level (1132.30 +/- 172.95x10(6) sperm). Furthermore, in the Maca-treated group exposed for 21 days to high altitude, epididymal sperm count was higher than in the non-treated group at sea level (690.49 +/- 43.67x10(6) sperm). In conclusion, treatment of rats with Maca at high altitude prevented high altitude-induced spermatogenic disruption.

Altitude↗

[Bilateral compartment syndrome after surgical perfusion for chronic ischemia of the lower extremities].

A 61-year-old man diagnosed with advanced stage Leriche syndrome underwent revascularization surgery with placement of an aortobifemoral shunt and prosthesis under combined general and lumbar epidural anesthesia. After 6 hours he developed bilateral lower extremity compartment syndrome with acute anuric kidney failure caused by severe rhabdomyolysis. Thirty hours after surgery the patient suffered cardiac arrest due to hyperkalemia and was unresponsive to advanced cardiopulmonary resuscitation. The delay in diagnosis, in part owing to the epidural block provided for surgery, and loss of muscle mass led to the unfavorable outcome in this case.

Acute Kidney Injury↗

Conservative elective treatment of upper urinary tract tumors: a multivariate analysis of prognostic factors for recurrence and progression.

PURPOSE: We evaluate the safety and efficacy of conservative elective treatment of upper urinary tract tumors, and determine predictive factors for recurrence and progression to optimize indications of this type of treatment. MATERIALS AND METHODS: Since 1984 we have performed a prospective study of conservative treatment of single, low grade and stage, less than 3 cm. upper tract tumors. The study includes 54 patients with a normal contralateral kidney who had been followed for more than 36 months. Open conservative surgery was performed in 31 cases and endourological surgery in 23. Minimum followup was 36 months, maximum 210 and mean 84.8. Univariate and multivariate analyses of recurrence and progression were performed in relation to age, sex, association with a bladder tumor, bladder tumor stage and grade, sequence of bladder tumor in relation to upper urinary tract tumor, number of previous bladder tumor recurrences, association with bladder carcinoma in situ, upper urinary tract tumor grade, stage, location, size and therapy, and upper urinary tract cytology. RESULTS: Of the 54 patients 19 (35%) had recurrence, which was bilateral recurrence in 4, and progression occurred in 9 (16%). At the end of analysis 44 (62.9%) patients were disease-free and alive at a mean time of 92.88 months, 13 (24%) died disease-free at a mean of 72.7 months and 7 (12.9%) died of disease at a mean of 97.85 months. Cause specific mortality occurred in 7 (12.9% cases). Among the 54 initially conservatively treated units 42 (77.7%) kidneys were ultimately preserved. On univariate and multivariate analysis tumor location in the renal pelvis and association with a previous multi-recurrent bladder tumor were variables significantly related to recurrence and progression, as well as bilateral recurrence. CONCLUSIONS: Conservative treatment is an optional approach for select upper urinary tract tumors. The strongest risk factors for recurrence and progression were association with a previous multi-recurrent bladder tumor and tumor location in the renal pelvis but these conditions were also the strongest risk factors for bilateral recurrence. Conservative treatment can also be recommended in these cases but only with compliant patients and close followup.

Adult↗

Late oncological occurrences following radical cystectomy in patients with bladder cancer.

PURPOSE: To evaluate the prognoses and predictive factors of late oncological occurrences and its impact on follow-up strategy in patients with bladder tumours treated with radical cystectomy. MATERIALS AND METHODS: Late oncological occurrences were considered when they took place after three years from cystectomy or when early recurrence was controlled with therapy and patients developed recurrence again after a three-year disease-free interval. Univariate and multivariate analysis of predictive factors for late oncological occurrences were carried out on 215 patients at risk of late oncological recurrences. RESULTS: Among 357 patients treated with cystectomy, 163 (45.6%) relapsed, 149 (41.7%) of them as early recurrence and 17 (4.7%) were considered as late oncological events. This incidence increased up to 8% when patients at risk were considered. Three patients with early recurrence reached a complete response after treatment and relapsed again as late recurrences. Distant metastases and local recurrence represented 78.5% of early recurrence as opposed to 11.7% in late oncological occurrences, whereas, extravesical urothelium recurrences represented 8.6% and 70% respectively (p<0.01). Among patients with late oncological occurrences, nine (53%) were disease-free, seven with urothelial recurrence and two of three with lymph-node recurrence whereas only eight (5.6%) patients with early recurrence were free of tumour (p<0.0001). Multiple tumours, prostate involvement and organ-confined tumours in cystectomy specimen were the independent variables for predicting late oncological occurrences in multivariate analysis. CONCLUSIONS: Recurrences in the remaining urothelium prevail as the pattern of late oncological occurrences. The prognosis of these events is significantly better than an early recurrence. Patients at risk of late oncological occurrences are those with multiple tumours, prostate involvement and with organ-confined tumours in cystectomy specimen. After three years from cystectomy, the follow-up schedule of these patients be limited to performing an annual CT-scan and urinary cytology to detect essentially upper urinary tract recurrence and extrapelvic lymph-nodal recurrence. Afterwards an annual intravenous urography might replace to CT-scan since lymph-nodal involvement was not detected.

Adult↗

Effect of high altitude exposure on spermatogenesis and epididymal sperm count in male rats.

The present study was designed to determine the effect of exposure to high altitude on spermatogenesis using transillumination technique and sperm count in male rats. In addition, the effect of oral intubation for intragastric administration of vehicle on testicular parameters in adult male rats in a schedule of 42 days was assessed. Male rats were exposed to Cerro de Pasco (Peru) at 4340 m for 3, 7, 14, 21, 28, 35 and 42 days resulting in a modification of the pattern of the seminiferous tubule stages. At day 3, stages I, IV-V, VI, VII and IX-XI were relatively shorter at high altitude than at sea level. At day 7, stages VIII, IX-XI, XII and XIII-XIV were reduced. At day 14, stages VII, VIII and IX-XI were reduced. At day 21 and 28, stages VIII, XII and XIII-XIV were significantly increased at high altitude. At day 35 an increase in stage XIII-XIV was observed. At day 42, stages II-III, IX-XI and XII were significantly increased at high altitude. Epididymal sperm count was significantly reduced at day 7 of exposure to high altitude and maintained low levels with respect to sea level up to 42 days. In conclusion, high altitude exposure affects spermatogenesis, particularly onset of mitosis and spermiation. This in turn affects epididymal sperm count.

Altitude↗

Clinical panurothelial disease in patients with superficial bladder tumors: therapeutic implications.

PURPOSE: We established the prognostic and therapeutic implications of panurothelial involvement in patients with superficial bladder tumors for optimizing therapeutic approaches in those at risk for panurothelial involvement. MATERIALS AND METHODS: We studied the records of 35 patients with clinical panurothelial disease. Since all of these patients presented with high risk superficial bladder cancer during followup, they were included in specific therapeutic and followup regimens. Radical procedures or conservative therapies were indicated mainly according to pathological examination and the recurrence pattern. RESULTS: Panurothelial involvement was a late stage of a recurrent and diffuse process that essentially developed in sequences, in which all patients presented with high risk superficial bladder tumors. This process involved continued relapse after panurothelial involvement developed. Notably 19 patients (79.1%) at risk for recurrence had repeat relapse in the urothelium. In the upper urinary tract 12 patients (34.3%) had bilateral involvement, including 7 (41.2%) of 17 patients after cystectomy. We identified 2 subgroups of patients. The subgroup with a better prognosis included 27 patients in whom late panurothelial disease developed step by step after a complete response to intravesical therapy, including 14 (51.8%) who were free of disease. The other subgroup with a poor prognosis included 8 patients with concurrent bladder carcinoma in situ and prostate involvement as well as early panurothelial disease, of whom only 2 (25%) were disease-free. All patients underwent many therapeutic approaches. A mean of 7.5 surgical procedures per patient were done, including a mean of 5.5 transurethral resections, a mean of 1 conservative approach to the upper urinary tract and a mean of 1.1 radical procedures. At a median followup of 111 months 10 patients (28.5%) were disease-free but only 7 (20%) retained the bladder, while 19 (54.3%) died of tumor. CONCLUSIONS: Patients with high risk superficial bladder multifocal tumors and associated bladder carcinoma in situ are at high risk for panurothelial involvement. Radical cystectomy may be recommended in these patients when initially or during followup, concurrent high risk superficial bladder tumors and prostate involvement develop or prostate involvement recurs. For the upper urinary tract conservative therapies may be advisable when noninfiltrating tumors are diagnosed even after cystectomy due to the high rate of bilateral new onset disease. When cystectomy is performed, extended excision of the upper urinary tract and pyelo-intestinal anastomosis may be considered.

Aged↗

The chorea of McLeod syndrome.

Among the movement disorders associated with acanthocytosis, McLeod syndrome (McKusick 314850) is the one that is best characterized on the molecular level. Its defining feature is low reactivity of Kell erythrocyte antigens. This is due to absence of membrane protein KX that forms a complex with the Kell protein. KX is coded for by the XK gene on the X-chromosome. We present six males (aged 29 to 60 years), with proven XK mutations, to discuss the chorea associated with McLeod syndrome. The movement disorder commonly develops in the fifth decade and is progressive. It affects the limbs, the trunk and the face. In addition to facial grimacing, involuntary vocalization can be present. In early stages there may only be some restlessness or slight involuntary distal movements of ankles and fingers. Lip-biting and facial tics seem more common in autosomal recessive choreoacanthocytosis linked to chromosome 9. This, together with the absence of dysphagia in McLeod syndrome, may help in differential diagnosis. Recent findings suggest a role for the endothelin system of the striatum in the pathogenesis of McLeod syndrome.

Adult↗

Neutron or photon irradiation for prostate tumors: enhancement of cytokine therapy in a metastatic tumor model.

We have shown that implantation of human prostate carcinoma PC-3 cells in the prostates of nude mice led to the formation of prostate tumors with metastases to para-aortic lymph nodes. We found that day 6 prostate tumors were responsive to systemic injections of interleukin 2 (IL-2) therapy. We have now investigated the combination of primary tumor irradiation and IL-2 for metastatic prostate cancer in this preclinical tumor model. The effect of neutron radiation was compared with that of photon radiation. Advanced prostate tumors (approximately 0.4 cm) were irradiated, and a day later, mice were treated with systemic IL-2 for three weekly cycles. In separate experiments, mice were either sacrificed on day 30 to assess prostate tumor size and tumor histology or followed for survival. A dose-dependent inhibition of prostate tumor growth was caused either by photons or neutrons, but neutrons were more effective than photons with a relative biological effectiveness of 2. The tumor inhibition obtained with 250 cGy neutrons and 500 cGy photons was significant (>75%) and was further increased (> or = 90%) by addition of IL-2 therapy. In survival studies, the combination of radiation and IL-2 showed a significant survival advantage compared with untreated mice (P < or = 0.005) or radiation alone (P < or = 0.003) and an increase in median survival compared with IL-2 alone. Histologically, the combined regimen resulted in a greater degree of tumor destruction, inflammatory response, and vascular damage than that observed with each modality alone. After this combined treatment, no tumor was histologically detected in the para-aortic lymph nodes of these mice, and the lymph nodes were significantly smaller. These findings showed that primary tumor irradiation, either with neutrons or photons, enhanced IL-2 therapeutic effect for the treatment of advanced prostate cancer. This combined modality induced an antitumor response that controlled the growth of prostate tumors and their metastases.

Adenocarcinoma↗