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Biomedical subjects

L Santiago

Publications and source records attributed to L Santiago.

At least 19 recordsLinked to original sources

Dedicated asthma center improves the quality of care and resource utilization for pediatric asthma: a multicenter study.

OBJECTIVES: To determine the relative effectiveness of pediatric asthma care among patients treated by a dedicated asthma center (AC) vs children who use the emergency department (ED) as a site of primary asthma care. METHODS: A retrospective case-control design was used. A random sample of AC cases was selected from a designated comprehensive AC over a 12-month period. Concurrent ED control patients were identified from all cases of pediatric asthma from five urban hospitals based on two or more ED visits. Cases and controls were matched (1:2) based on age and National Heart, Lung, and Blood Institute (NHLBI) asthma severity of illness classification. A telephone survey was administered to the caregivers of all enrolled patients in the study sample. RESULTS: Four elements of pediatric asthma care were examined: quality, access, hospital utilization, and functional impact of disease. Demographic data were similar between the ED cases and the AC controls. In terms of quality of care, the AC patients were more likely to use maintenance antiinflammatory medications, 60.2% vs 22.5% (OR = 5.3; 95% CI = 2.9 to 9.7) and more likely to be taking medications at school, 71.4% vs 48.1% (OR = 2.7; 95% CI = 1.5 to 4.7). In terms of access to care, the AC families were more likely to have a physician to call to assist with outpatient management, 98.2% vs 65.0% (OR = 25.3; 95% CI = 9.0 to 76.9). Frequent ED utilization (> or = 1 visit/month) was less likely in the AC patients, 9.2% vs 22.0% (OR = 0.35; 95% CI = 0.16 to 0.79) and school absenteeism was lower as well (9.5 +/- 6.7 days vs 16.6 +/- 10.3, p < 0.001). Additionally, the caregivers of the AC patients missed fewer workdays (4.7 +/- 2.8 vs 7.4 +/- 4.1; p = 0.03). CONCLUSIONS: Significant disparities in quality, access, resource utilization, and functional impact exist between AC and ED patients. Emergency physicians have a unique opportunity to improve the public health by directing ED patients toward pediatric AC treatment.

Absenteeism↗

Evidence for the involvement of two different MHC class II regions in susceptibility or protection in allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a disease with uncertain pathology. Studies have suggested a pathogenic role for T(H)2 cells. Previously, we demonstrated, in a small group of patients, that T(H)2 reactivity to a major Aspergillus fumigatus antigen was restricted by HLA-DR2 or HLA-DR5 alleles. OBJECTIVES: We sought to confirm whether susceptibility to ABPA is exclusively associated with HLA-DR locus and to investigate the involvement of HLA-DQ genes in the development of ABPA. METHODS: Genomic DNA was extracted from patients with ABPA, patients without ABPA but with positive A fumigatus skin test responses and asthma or cystic fibrosis, and healthy control subjects. HLA-DR and HLA-DQ genes were detected by using low-resolution typing; high-resolution typing was done only on HLA-DR2- and HLA-DR5-positive individuals by using sequence-specific primers (PCR-SSP). RESULTS: A significantly higher frequency of HLA-DR2 was observed in patients with ABPA versus those without ABPA (corrected P <.01) or healthy control subjects (corrected P <.01). Genotype analysis revealed that susceptibility to ABPA is associated with HLA-DR2 alleles DRB1*1503 and DRB1*1501 and, to a lesser extent, with the HLA-DR5 allele DRB1*1104. The presence of DR4 or DR7 alleles in non-DR2/5 patients with ABPA suggests that these alleles may also be contributing factors in this disease. Another striking observation was the significantly high frequency of HLA-DQ2 in patients without ABPA (67. 4%) compared with patients with ABPA (20.5%) and normal control subjects (37.7%), suggesting that these alleles may confer protection in the population without ABPA. CONCLUSION: These genetic studies suggest that HLA-DR molecules DR2, DR5, and possibly DR4 or DR7 contribute to susceptibility while HLA-DQ2 contributes to resistance and that a combination of these genetic elements determines the outcome of ABPA in patients with cystic fibrosis and asthma.

Alleles↗

Salivary cortisol as a tool for physiological studies and diagnostic strategies.

Salivary cortisol is an index of plasma free cortisol and is obtained by a noninvasive procedure. We have been using salivary cortisol as a tool for physiological and diagnostic studies, among them the emergence of circadian rhythm in preterm and term infants. The salivary cortisol circadian rhythm in term and premature infants was established between 8 and 12 postnatal weeks. In the preterm infants the emergence of circadian rhythm was parallel to the onset of sleep rhythm. We also studied the use of salivary cortisol for screening for Cushing's syndrome (CS) in control and obese outpatients based on circadian rhythm and the overnight 1 mg dexamethasone (DEX) suppression test. Salivary cortisol was suppressed to less than 100 ng/dl after 1 mg DEX in control and obese patients. A single salivary cortisol measurement at 23:00 h and again after 1 mg DEX above the 90th percentile of the obese group values had sensitivity and specificity of 93 and 93% (23:00 h), and 91 and 94% (after DEX), respectively. The sensitivity improved to 100% when we combined both parameters. We also studied 11 CS children and 21 age-matched primary obese children for whom salivary cortisol sensitivity and specificity were 100/95% (23:00 h), and 100/95% (1 mg DEX), respectively. Similar to adults, sensitivity and specificity of 100% were obtained by combining 23:00 h and 1 mg DEX. The measurement of salivary cortisol is a useful tool for physiological studies and for the diagnosis of CS in children and adults on an outpatient basis.

Adolescent↗

Laparoscopic management of indeterminate renal cysts.

OBJECTIVES: We present our follow-up of patients with indeterminate renal cysts who were initially evaluated laparoscopically. We specifically address those patients discovered to have cystic renal cell carcinoma by laparoscopy and the incidence of tract seeding, local recurrence, and distant metastases. METHODS: Between July 1993 and September 1997, 35 patients with indeterminate renal cysts were evaluated laparoscopically. Under laparoscopic visualization, the cyst was located and aspirated, the fluid was sent for cytology, and the floor of the cyst was biopsied. The tissue was then evaluated immediately by one of our genitourinary pathologists, and an intraoperative decision was made. Four patients were found to have cystic renal cell carcinoma and underwent partial or radical nephrectomy in the same setting. An additional patient had a delayed partial nephrectomy 10 days after laparoscopy as a result of change in the final pathology reading. The patients with malignancy were followed with chest x-ray, liver function tests, abdominal computed tomography (CT) scans, and physical examination every 3 months for the first year and then every 6 months thereafter. The average follow-up was 20.2 months (range 8 to 30). RESULTS: Of the 35 patients evaluated in this manner, 5 (14%) were found to have cystic renal cell carcinoma. There has been no evidence of local recurrence or metastatic disease to date. Physical examinations, chest x-rays, liver function tests, and abdominal CT scans all remain negative. CONCLUSIONS: Initial laparoscopic evaluation of complex cysts can save the patient from undergoing needless open surgery. Laparoscopic biopsy of cystic renal cell carcinoma followed by open surgery does not seem to increase the incidence of peritoneal seeding, tract recurrence, or distant metastases. Although the preliminary results are very encouraging, long-term follow-up is clearly necessary.

Adolescent↗

Construction of attenuated HIV-1 accessory gene immunization cassettes.

Delivery of genetic expression cassettes into animals can effectively induce both humoral and cellular immunity to the expressed gene product. Previously, we used this strategy to immunize against HIV-1 structural and enzymatic proteins in mice, non-human primates and in humans. In contrast, the use of the accessory genes including vif, vpr, vpu and nef as immunotherapeutic vaccine targets has not been well characterized. Our goal is to design an effective genetic HIV vaccine, which includes the accessory genes as part of a multi-component immunogen. In order to develop accessory genes as genetic vaccines, we have molecularly cloned and analysed the sequence variation and immunogenic potential present in these genes derived from viral isolates obtained from HIV-1 infected patients and laboratory isolates. Prototype genetic variants were selected and their ability to induce humoral and cellular immune responses was studied in animal models. We observed that attenuated accessory genes can effectively induce both humoral and cellular responses in mice and the resulting immune response is directly correlated with DNA concentrations delivered and the number of boosts. This strategy can be used generally to develop an effective, safe DNA vaccine for any pathogen.

AIDS Vaccines↗

Urinary IL-6 is elevated in patients with urolithiasis.

PURPOSE: To evaluate the possible role of cytokines interleukin (IL)-1beta, IL-1alpha and IL-6 in patients with urolithiasis. MATERIALS AND METHODS: Fifty-six patients currently with stone disease, 63 patients with bacterial cystitis, and 66 normal individuals were evaluated for urinary IL-1alpha, IL-1beta and IL-6. Clean catch urine samples were obtained and evaluated for cytokine levels using enzyme immunoassays for the respective cytokines. Statistical analysis of the results was carried out using the Kruskal-Wallis test followed by Newman-Keuls test and the chi-squared test. RESULTS: The patients with stone disease had significant elevations in IL-6 (p value< 10(-7)) relative to normal subjects. The levels of IL-6 in stone patients were lower than those of patients with bacterial cystitis. Neither IL-1beta nor IL-1alpha was elevated in stone patients relative to normals. By contrast, bacterial cystitis patients showed significant elevations in all three cytokines relative to normal subjects. Chi-squared analysis confirmed that stone patients had elevated IL-6 without elevation in either IL-1alpha or IL-1beta relative to normal subjects. CONCLUSIONS: Stone patients show significant elevations in IL-6 without marked increases in either IL-1beta or alpha relative to normal subjects. This elevation in IL-6 is not from infection as is seen in bacterial cystitis subjects. The elevation in IL-6 may be useful in the understanding of the pathogenesis of urolithiasis or as a potential marker for stone disease and we are currently investigating these possibilities.

Cystitis↗

The association of HLA-DR alleles and T cell activation with allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by the mold Aspergillus fumigatus. We previously reported that the majority of T cell clones (TCC) isolated from three ABPA patients, and specific for a dominant Ag of A. fumigatus, Asp f 1, were IL-4-producing CD4+ Th2 cells capable of responding to Ag in association with the HLA-DR subtypes DRB1*1501, *1503, and *1601 for HLA-DR2, and DRB1*1101, *1104, and *1202 for HLA-DR5. In the present study we extended the previous findings to determine whether the observed restriction with the HLA-DR2/5 subtypes held importance in a larger patient population. Serotyping revealed that 16 of 18 ABPA patients were either HLA-DR2, HLA-DR5, or both. Compared with a normal control population, the frequencies of HLA-DR2 (50 vs 22.3%) and HLA-DR5 (44.4 vs 19.8%) were significantly increased in these ABPA patients. Genotype analyses of an additional 15 patients identified the same HLA-DR subtypes previously shown functional for Asp f 1 Ag presentation. The relative avidities of Asp f 1 peptides for the purified HLA-DR subtypes, DRB1*1501 (functional) and DRB1*1502 (nonfunctional), were examined to determine whether differential binding to the HLA-DR subtypes explains successful Ag presentation. Similar low binding avidities were detected for both HLA-DR subtypes, indicating that the functionality cannot be simply explained by differences in binding affinities. Thus, the limited number and their role in Ag presentation emphasizes the possibility that the six identified HLA-DR subtypes are important in the pathophysiology of ABPA.

Alleles↗

Modified Pereyra bladder neck suspension: 10-year mean followup using outcomes analysis in 125 patients.

PURPOSE: We attempt to determine the long-term success rate of the modified Pereyra bladder neck suspension, identify preoperative factors predictive of long-term outcome, and investigate the influence of method and length of followup on reported continence status after modified Pereyra bladder neck suspension. MATERIALS AND METHODS: The charts of 177 patients who underwent modified Pereyra bladder neck suspension at our institution more than 5 years ago were reviewed. An attempt was made to contact all patients either by mail or telephone to complete a patient survey questionnaire. RESULTS: Of 177 patients 125 (71%) completed the patient survey with a mean followup of 9.8 years. At survey followup 20% of the patients reported no incontinence of any type and 51% reported stress urinary incontinence with or without urge incontinence. Of the patients 71% reported significant improvement in the incontinence and 73% were satisfied with the results of the procedure. No accurate preoperative predictors of long-term outcome were identified. The method and length of followup had significant impact on reported continence status after modified Pereyra bladder neck suspension. CONCLUSIONS: This long-term study using outcomes analysis reveals a high rate of recurrent stress incontinence after modified Pereyra bladder neck suspension. However, most patients maintain significant subjective improvement and remain satisfied with the results of the operation.

Female↗

Dihydropyridine receptor mutations cause hypokalemic periodic paralysis.

Hypokalemic periodic paralysis (hypoKPP) is an autosomal dominant skeletal muscle disorder manifested by episodic weakness associated with low serum potassium. Genetic linkage analysis has localized the hypoKPP gene to chromosome 1q31-q32 near a dihydropyridine (DHP) receptor gene. This receptor functions as a voltage-gated calcium channel and is also critical for excitation-contraction coupling in a voltage-sensitive and calcium-independent manner. We have characterized patient-specific DHP receptor mutations in 11 probands of 33 independent hypoKPP kindreds that occur at one of two adjacent nucleotides within the same codon and predict substitution of a highly conserved arginine in the S4 segment of domain 4 with either histidine or glycine. In one kindred, the mutation arose de novo. Taken together, these data establish this DHP receptor as the hypoKPP gene. We are unaware of any other human diseases presently known to result from DHP receptor mutations.

Alleles↗

The corpus cavernous electromyography in the erectile dysfunction diagnosis.

The single potential analysis of cavernous electric activity (CC-EMG), registration bands were studied in 144 patients with erectile dysfunction followed from November 1992 to March 1993. We attempted to correlate abnormal electromyographic records with reduction of the cavernous bodies and albuginea expansibility, as measured by cavernosometry/rigidometry. In this selected group of patients, with venous leak of different flow, the main associated causes of the erectile dysfunction were cavernous neuromyopathy (91), diabetes mellitus (20), disturbances of the arterial influx (7), endocrinological factors (4), Peyronie's disease (3). Some patients (15) presented with a penile bend. A history of alcohol and tobacco use was obtained: 38 patients smoked 15 to 60 cigarettes/day and 43 patients drank moderate to heavy. The coexistence of other pathologies, has been investigated, showed many other associated diseases. The study attempts to determine if some electromyographic standards in patients with erectile dysfunction, could, by themselves, be a formal indication to penile implant, for a PGE1 self-injection program or for use of a vacuum device. Our results suggest that at least in some cases CC-EMG studies may be clinically relevant and allow choice of optimal therapy.

Action Potentials↗

Three-day treatment of typhoid fever with two different doses of ceftriaxone, compared to 14-day therapy with chloramphenicol: a randomized trial.

Fifty-nine adult Filipino patients suffering from typhoid fever documented by blood culture were randomly allocated to one of three different drug regimens. Nineteen patients received 3 g ceftriaxone iv once daily for three days. Twenty patients received 4 g ceftriaxone iv once daily for three days and 20 patients received oral chloramphenicol 3 g daily in divided doses for two days followed by 2 g daily for 12 days. Eighteen patients were cured (95%) with 3 g of ceftriaxone for three days. All patients receiving 4 g ceftriaxone per day for three days or chloramphenicol for 14 days were cured. In the ceftriaxone groups two patients developed typhoid fever 30 and 45 days respectively after completion of treatment and one further patient had evidence of reinfection. Three patients relapsed within 15 to 17 days in the chloramphenicol group. Fever subsided in most patients between six and eight days, with three patients having a prolonged and moderate fever for 11 days in the ceftriaxone groups. This study suggests that a short treatment of three days of typhoid fever with ceftriaxone (3 or 4 g once daily) is adequate and not hazardous as far as relapses are concerned.

Adolescent↗

Prenatal diagnosis and carrier detection of a cryptic translocation by using DNA markers from the short arm of chromosome 5.

DNA markers from the short arm of chromosome 5 were used to examine a large family in which a microscopically undetectable translocation was segregating. In addition to confirming that three retarded children were hemizygous for loci distal to 5p14, these analyses identified five individuals as being carriers of the balanced translocation. The use of molecular probes provided informed genetic counseling to the family for the first time. With the DNA markers from 5p, prenatal diagnosis was performed on two fetal chorionic villus samples, both of which were found to have unbalanced karyotypes. The identification of translocation carriers was complicated by recombination between the small translocated segment of 5p and the corresponding region on the normal homologue, which changed the haplotype of the translocated 5p segment.

Animals↗