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Biomedical subjects

C Hernandez

Publications and source records attributed to C Hernandez.

At least 55 records · Page 3Linked to original sources

Treatment of non-resectable malignant iris tumours with custom designed plaque radiotherapy.

BACKGROUND: Plaque radiotherapy is the most common method of managing posterior uveal melanoma but its use for iris melanoma and iris metastases has not yet been evaluated. METHODS: Fourteen patients with non-resectable iris melanoma and four with iris metastasis were treated with plaque radiotherapy. The tumour response to treatment and the local side effects of the radioactive plaque were evaluated. RESULTS: In the iris melanoma group over a mean follow up of 26 (range 6-75) months, the tumour regressed in 13 of the 14 patients (93%) and recurred as diffuse seeding in one patient (7%). Despite large doses of radiation given transcorneally, the cornea developed epitheliopathy, abrasion, and oedema in only one case each. The major radiation side effects were localised iris vasculopathy without glaucoma in two cases, posterior synechiae in five cases, and cataract in six cases. In the iris metastasis group, tumour regression was observed in all four patients (100%) and radiation side effects were not evident over the relatively short mean follow up period of 8 (range 4-9) months. All of the 14 patients with irradiated iris melanoma have remained systemically healthy without metastasis while three of the four patients with irradiated iris metastases have died of metastases from the primary neoplasm. CONCLUSION: Custom designed plaque radiotherapy appears to be an effective alternative method of controlling non-resectable diffuse iris melanoma and solitary iris metastasis and has relatively few side effects.

Brachytherapy↗

Inhibition of tumoral cell respiration and growth by nordihydroguaiaretic acid.

The effects of nordihydroguaiaretic acid (NDGA), best known as an inhibitor of lipoxygenase activities, on the culture growth, oxygen consumption, ATP level, viability, and redox state of some electron carriers of intact TA3 and 786A ascites tumor cells have been studied. NDGA inhibited the respiration rate of these two tumor cell lines by preventing electron flow through the respiratory chain. Consequently, ATP levels, cell viability and culture growth rates were decreased. NDGA did not noticeably inhibit electron flow through both cytochrome oxidase and ubiquinone-cytochrome b-c1 complex. Also, the presence of NDGA changed to redox state of NAD(P)+ to a more reduced level, and the redox states of ubiquinone, cytochrome b and cytochromes c + c1 changed to a more oxidized level. These observations suggest that the electron transport in the tumor mitochondria was inhibited by NDGA at the NADH-dehydrogenase-ubiquinone level (energy-conserving site 1). As a consequence, mitochondrial ATP synthesis would be interrupted. This event could be related to the cytotoxic effect of NDGA.

Adenosine Triphosphate↗

Validation of the medical expert system RENOIR.

RENOIR is an expert system developed to assist the diagnosis of 37 diseases of connective tissue and inflammatory arthropathies. Precise diagnosis of rheumatic diseases implies great uncertainty and there is no gold standard with which to compare the expert system output. To overcome this problem a set of clinical cases was submitted to RENOIR and its diagnoses were compared with those of clinicians. Medical records of 81 patients with rheumatic diseases were interpreted by RENOIR and by 12 clinicians at three different expertise levels in rheumatology. Distances between the likelihoods of the 37 considered diseases provided by clinicians and RENOIR were computed as a disagreement measure. Mahalanobis distance was used to correct the collinearity between the possibilities of each pair of diseases. Using the resulting matrices of distances between experts, cluster analyses were carried out to classify RENOIR among human experts. Greater differences between RENOIR and clinicians than among clinicians themselves were not found.

Cluster Analysis↗

Modification of the effect of tamoxifen, cis-platin, DTIC, and interferon-alpha 2b on human melanoma cells in culture by a mixture of vitamins.

The effect of a mixture of vitamins in modifying the efficacy of commonly used drugs in the treatment of human melanoma has not been studied. Vitamin C and d-alpha-tocopheryl succinate (alpha-TS) alone reduced the growth of human melanoma (SK-30) cells in culture, whereas beta-carotene (BC), 13-cis-retinoic acid (RA), or sodium selenite alone was ineffective. RA caused morphological changes, as evidenced by flattening of cells and formation of short cytoplasmic processes. A mixture of four vitamins (vitamin C, BC, alpha-TS, and RA) was more effective in reducing growth of human melanoma cells than a mixture of three vitamins. The growth-inhibitory effect of cis-platin, decarbazine, tamoxifen, and recombinant interferon-alpha 2b was enhanced by vitamin C alone, a mixture of three vitamins (BC, alpha-TS, and RA), and a mixture of four vitamins (vitamin C, BC, alpha-TS, and RA) that contained 50 micrograms/ml of vitamin C. These data show that a mixture of three or four vitamins can enhance the growth-inhibitory effect of currently used chemotherapeutic agents on human melanoma cells.

Ascorbic Acid↗

Biocidal efficacy of a flocculating emergency water purification tablet.

Chlor-Floc (CF) emergency water purification tablets were tested for bactericidal, virucidal, and cysticidal efficacy in water at temperatures ranging from 5 to 25 degrees C. The minimal required log reduction was achieved for bacteria, Giardia muris, and rotavirus, but CF did not achieve the required log reduction of poliovirus at any of the temperatures or times investigated. The biocidal properties of the CF tablet were equivalent to if not greater than those of the Globaline iodine tablet, and the CF tablet was a more rapid cysticide under several potential use conditions. Therefore, it is a suitable substitute for iodine tablets for emergency purification of drinking water. Clarification of turbid waters was effective, but filtration through a cloth is necessary to prevent flocculated sediment from entering the canteen. The CF tablets met military requirements for emergency water purification and are safe and acceptable for use by the military.

Journal Article↗

Cataractogenesis after Cobalt-60 eye plaque radiotherapy.

PURPOSE: This study was designed to estimate the actuarial incidence of typical postirradiation cataracts and to identify prognostic factors related to their development in melanoma-containing eyes treated by Cobalt-60 plaque radiotherapy. Our special interest was the impact of calculated radiation dose and dose-rate to the lens. METHODS AND MATERIAL: The authors evaluated the actuarial occurrence of post-irradiation cataract in 365 patients with primary posterior uveal melanoma treated by Cobalt-60 plaque radiotherapy between 1976 and 1986. RESULTS: Only 22% (S.E. = 4.6%) of the patients who received a total dose of 6 to 20 Gy at the center of the lens developed a visually significant cataract attributable to the radiation within 5 years after treatment. Using multivariate Cox proportional hazards modeling, the authors identified thickness of the tumor, location of the tumor's anterior margin relative to the equator and the ora serrata, and diameter of the eye plaque used as the best combination of covariables for predicting length of time until development of cataract. Surprisingly, the dose of radiation delivered to the lens, which was strongly correlated to all of these covariables, was not a significant predictive factor in multivariate analysis. CONCLUSION: The results suggest that success of efforts to decrease the occurrence rate of post-irradiation cataracts by better treatment planning might be limited in patients with posterior uveal melanoma.

Adult↗

Regression of retinoblastoma after plaque radiotherapy.

A review of 400 consecutive patients with retinoblastoma disclosed that 103 tumors in 103 eyes were treated with solitary plaque radiotherapy. The tumors were from 1 to 16 mm (mean, 7 mm) in basal diameter and from 1 to 8 mm (mean, 4 mm) in thickness. Thirty-one tumors were treated with plaque radiotherapy as initial treatment, whereas 72 tumors were treated with plaque radiotherapy as secondary treatment after failure of other methods. Of the 102 tumors on which adequate follow-up data were available, all responded initially to plaque radiotherapy with tumor regression. Over the mean follow-up of 38 months (range, six to 192 months), 89 tumors (87%) showed persistent regression and 13 (13%) showed tumor recurrence. The recurrence occurred at a mean interval of five months (range, one to 11 months) after plaque radiotherapy. A statistical analysis of tumor size, tumor location, tumor proximity to the optic disk and foveola, presence of vitreous seeds, radioactive plaque diameter, plaque shape, radioisotope, and primary or secondary treatment disclosed no important predictors of tumor recurrence. Carefully selected retinoblastoma, even juxtapapillary and macular tumors and those with localized vitreous seeds, can be successfully treated with plaque radiotherapy.

Brachytherapy↗

A rule-based postoperative pain controller: simulation results.

We describe a system for controlling postoperative pain, a phenomenon that is difficult to treat by conventional control methods due to interpatient variability, interferences, non-linearity and the lack of a plausible, well-defined mathematical model. The system consists of two phases. In Phase 1 a closed-loop fuzzy controller implementing a suitable control strategy brings the patient to a zero-pain state. In Phase 2, an open-loop computer-assisted continuous infusion controller maintains a constant concentration of the analgesic (alfentanil) in plasma, subject to an upper safety limit on infusion rate; the set-point of this controller is periodically revised (either maintained or reduced) on the basis of feedback on the duration of zero pain (set-point reduction is necessary because the open-loop system has no means of knowing whether analgesic is accumulating in the patient). Pain is quantified by the patient on a numerical scale of 1 to 10 at 1.5-min intervals during Phase 1 and 9-min intervals during Phase 2. In simulation trials in which a fixed approximate model was used for the effect of sedation on pain while the pharmacokinetics of alfentanil were varied from one simulated patient to another, zero pain was achieved in under 15 min with minimal overshoot in plasma drug concentration and was maintained, with only minor deviation, by means of low drug concentrations.

Alfentanil↗

Plaque radiotherapy in the management of retinoblastoma. Use as a primary and secondary treatment.

BACKGROUND: Radioactive episcleral plaque brachytherapy is a treatment method for selected retinoblastomas. The authors have used this technique since 1976 as both a primary and a secondary treatment method after other methods failed to achieve tumor control. METHODS: A review of the records of 400 consecutive children with retinoblastoma showed that solitary plaque radiotherapy was used as a method of management in 103 cases. The authors' overall experience was evaluated, and the results between primary and secondary plaque therapies were compared in these 103 cases. RESULTS: Of the 103 tumors, the mean basal diameter was 7 mm, and the mean thickness was 4 mm. Overlying vitreous seeds were clinically apparent in 50 cases (48%). The mean proximity of the tumor margin to the optic disc margin was 6 mm and to the foveola was 6 mm. The mean follow-up period was 40 months. In 89 cases (86%), the tumor was controlled by one plaque application, whereas in 13 cases (13%), tumor recurrence after initial tumor shrinkage necessitated subsequent treatment. Final visual outcome was good in 63 cases (62%), poor in 30 (29%), enucleation in 9 (9%), and unknown in 1 case. The poor vision was due to foveal retinoblastoma (with or without amblyopia) in 25 cases (83%). Eight of the nine enucleated eyes were treated initially with external beam radiotherapy then later with plaque radiotherapy. In 31 cases (30%), plaque radiotherapy was used as a primary treatment to the tumor, while in 72 cases (70%), it was a secondary form of management after failure of other methods to control the tumor. Statistical analysis showed that tumors treated with plaque radiotherapy as a primary measure were more likely to be larger in in base (P = 0.01) and thickness (P = 0.01) than secondary treated tumors. The secondary treated retinoblastomas were more likely to have vitreous seeds (P = 0.02) than the primary treated tumors. The rate of tumor control and patient survival was similar between the two groups. CONCLUSION: Plaque radiotherapy is very effective in treating selected retinoblastomas with a high rate of tumor control and patient survival. It can be used successfully as a primary or a secondary treatment for tumors that have not been adequately controlled by other therapeutic methods.

Brachytherapy↗

Incidence of dysplasia and carcinoma of the uterine cervix in an Appalachian population.

BACKGROUND: Cervical cancer mortality rates in the Appalachian population of southeastern Kentucky have been shown to be unusually high. To better understand the high cervical cancer death rate in this area, we developed a population-based cervical disease registry. PURPOSE: This study describes the incidence of cervical dysplasia, carcinoma in situ, and invasive cervical cancer in 1986 and 1987 among White women in a 36-county area of Appalachian Kentucky based on histologic diagnoses. METHODS: We compared average annual age-adjusted incidence rates for carcinoma in situ and invasive cervical cancer in the study area with those for women in the Surveillance, Epidemiology, and End Results (SEER) Program. RESULTS: The incidence rate of invasive cervical cancer for women in the study area (14.9 per 100,000) was nearly twice that for White women in the SEER population (7.8 per 100,000), but it was similar to that for Black women in the SEER population (15.3 per 100,000). The incidence of carcinoma in situ for women in the study population (38.2 per 100,000) was 21% higher than that for White women (31.5 per 100,000) or for Black women (31.2 per 100,000) in the SEER population. The average annual age-adjusted incidence rate for all grades of dysplasia among women in the study population was 194.6 per 100,000. No comparable population-based incidence rates for dysplasia could be identified. CONCLUSIONS: Cervical cancer incidence rates are higher in Appalachian Kentucky than in the SEER population. Poverty appears to be a factor associated with these rates. IMPLICATIONS: Low-density populations such as those in rural Appalachia deserve greater attention in cancer control research. The population-based cervical dysplasia rates reported here may be useful for comparisons in future investigations.

Appalachian Region↗

Substance P in the regulation of mucociliary transport in the frog palate.

1. Mucociliary transport of carbon particles across the palate of anesthetized Rana pipiens was accelerated by electrical stimulation of the palatine nerve. 2. Transport was also accelerated by intracardiac injection of acetylcholine and of substance P in a dose-dependent manner. 3. Acceleration of transport by acetylcholine and by substance P was selectively blocked by atropine and by the substance P antagonist Spantide, respectively. 4. Acceleration of transport by nerve stimulation was blocked partially by atropine and by Spantide, and completely by the two administered concurrently. 5. It is concluded that nerve stimulation releases both acetylcholine and substance P or a similar neuropeptide. 6. Taken in conjunction with the literature, the data suggest that these substances are involved in the normal mechanism for stimulating mucociliary clearance of the palate in response to the presence of particles.

Acetylcholine↗

Role of glycosylation and deglycosylation in biosynthesis of and resistance to oleandomycin in the producer organism, Streptomyces antibioticus.

Cell extracts of Streptomyces antibioticus, an oleandomycin producer, can inactivate oleandomycin in the presence of UDP-glucose. The inactivation can be detected through the loss of biological activity or by alteration in the chromatographic mobility of the antibiotic. This enzyme activity also inactivates other macrolides (rosaramicin, methymycin, and lankamycin) which contain a free 2'-OH group in a monosaccharide linked to the lactone ring (with the exception of erythromycin), but not those which contain a disaccharide (tylosin, spiramycin, carbomycin, josamycin, niddamycin, and relomycin). Interestingly, the culture supernatant contains another enzyme activity capable of reactivating the glycosylated oleandomycin and regenerating the biological activity through the release of a glucose molecule. It is proposed that these two enzyme activities could be an integral part of the oleandomycin biosynthetic pathway.

Anti-Bacterial Agents↗

Hyperoxia-induced airway hyperresponsiveness and remodeling in immature rats.

We exposed 21-day-old rats to either normoxia or hyperoxia (greater than 95% O2) for 8 days and assessed in vivo airway responsiveness to aerosolized and intravenous methacholine (MCh) and airway architecture. Airway responsiveness was determined using a plethysmographic method. Hyperoxia increased airway cholinergic responsiveness, as reflected in a decreased mean ED200 (concentration of MCh required to increase respiratory system resistance by 100%) for both aerosolized MCh [air exposed, 5.94 +/- 2.50 vs. O2 exposed, 0.29 +/- 3.34 (SD) mg/ml, P = 0.0013, unpaired t test] and intravenous MCh (air, 1.40 x 10(-8) vs. O2, 2.45 x 10(-10) mol/kg, P = 0.0002). Airway morphometry was studied in a separate cohort of animals. After fixation by distension with Formalin at 25 cmH2O pressure, each airway cross section was photographed, and airway circumference, epithelial area, and smooth muscle layer area were determined by means of contour tracing using a digitizing pad and microcomputer. For the small airways (circumference less than 1,000 microns), hyperoxia increased both mean epithelial thickness (air, 4.88 +/- 0.53; O2, 8.64 +/- 0.90 microns) and mean smooth muscle layer thickness (air, 2.69 +/- 0.11; O2, 4.79 +/- 0.56 microns; P less than 0.0001 for each). O2 had similar effects on the larger (1,000-3,000 microns) central airways (P less than 0.0001 for both layers). We conclude that chronic hyperoxic exposure induces both airway hyperresponsiveness and airway wall thickening in immature rats.

Aerosols↗