A cross-sectional study of vitamin C intake and blood pressure in the elderly.

Data collected as part of a study designed to examine the nutritional status of non-institutionalized elderly individuals, ages 60-100 years, residing in the Boston area were used to investigate the relationship between blood pressure (BP) and vitamin C intake reported by three-day diet records. Four hundred and ten subjects not taking antihypertensive medications were grouped into 5 categories of vitamin C intake: < 60, 60-119, 120-179, 180-239, > or = 240 mg/day. Relative differences in systolic and diastolic BP between subjects consuming > or = 240 mg/day compared to those consuming < 60 mg/day were -6.9% (p < 0.05) and -6.6% (p < 0.05), respectively. The prevalence of elevated BP (systolic > or = 160 mmHg or diastolic > or = 100 mmHg) was approximately 50% lower (p < 0.05) across this range of vitamin C intake. Adjustment of these associations for age, sex, body mass, smoking, dietary sodium:potassium ratio, and other dietary factors did little to alter the relationship between vitamin C and BP. These results lend support to the hypothesis that vitamin C and BP are related, but further research is required to test whether the relationship is causal.     

In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models and antimalarial activity of major metabolites on Plasmodium falciparum.

Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.     

Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.

We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.     

Pelvic floor muscle training with biofeedback and bladder training in elderly women: a feasibility study.

OBJECTIVE: It is generally assumed that interventions used to treat urinary incontinence (UI) in young women could simply be applied to older competent and motivated women, but these assumptions have not been formally tested. The purpose of this study was to determine the feasibility of using physical therapies to treat UI in older women. DESIGN: Twelve-week time series. SETTINGS AND SUBJECTS: We recruited women older than 75 years with UI from an outpatient urology clinic and a waiting list for incontinence surgery. METHODS: After a baseline evaluation, the women collected data on their incontinence symptoms and bladder habits for 3 weeks using the 72-hour voiding diary and the 24-hour pad test. They then received 6 physical therapy treatments consisting of a combination of bladder training and pelvic floor muscle training assisted with biofeedback for 6 weeks. This was followed by another 3-week period of data collection and a final evaluation. RESULTS: Ten women participated in the study; 7 completed it. They were all comfortable with the treatment. They complied with the study demands in terms of attendance at treatment session (100%), data collection (96%), and completion of exercises at home (82%). The authors observed a decrease in the number of incontinent and urgency episodes. CONCLUSION: This preliminary study demonstrates that some women older than 75 years are good candidates to undertake physical therapies for UI and follow study demands. Random controlled studies that include this population will provide evidence regarding the effectiveness of these therapies.     

Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer

Rhenium-186 hydroxyethylidene diphosphonate (¹⁸⁶Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using ¹⁸⁶Re-HEDP Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the ¹⁸⁶Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq ¹⁸⁶Re-HEDP showed grade 3 toxicity (thrombocytes 25–50 × 10⁹/1), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% ± 10% IUA; range: 11%–44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of ¹⁸⁶Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of ¹⁸⁶Re-HEDP has been initiated.     

Magnetic resonance imaging of the craniocervical junction

Magnetic resonance imaging has become the study of choice for the majority of abnormalities of the craniocervical junction as well as for demonstration of primary pathology of the spinal cord, and brain stem. Although the applications of MR are currently limited by its high cost, relatively long scan time, and low sensitivity to calcification, new pulse sequences, faster scan strategies, and lower cost MR scanner are changing this situation. MR contrast agents and the use of 3-D imaging techniques combined with gradient echoes promise to play a role in MR of the craniocervical junction in the near future.     

Fertilization and early embrology: Monozygotic twinning in the human is associated with the zona pellucida architecture

Six cases of identical twin pregnancies which occurred in 2163cycles of in-vitro fertilization during a 3 year period arereported. Monozygosity was confirmed when the number of fetusesexceeded the number of embryos replaced (n = 4) or when twoconcepti were observed in a single amniotic sac (n = 2). Eachof the reported pregnancies resulted from replacement of embryoseither with naturally thin zonae pellucida or embryos whosezonae had been breached during micromanipulation for assistedfertilization (subzonal sperminsertion) or assisted hatching.That such cases exclusively gave rise to monozygosity suggestsa link between the physical state of the zona pellucida, hatching,and generation of identical twins.     

In vivo fluorescence spectroscopy and imaging of human skin tumours

The feasibility of using in vivo autofluorescence for the diagnosis of skin cancer was evaluated. In vivo fluorescence measurements were performed on healthy human volunteers, and patients with different types of benign and malignant skin tumours. Fluorescence spectra as well as fluorescence images were acquired. The excitation-emission matrix of normal skin (n=3) showed a broad peak at the shortest excitation wavelength (365 nm) and at 440 nm fluorescence wavelength, smoothly decreasing towards longer excitation and fluorescence wavelengths. Non-melanoma skin tumours (n=31) and control skin excited with 375 nm showed a broad fluorescence band from 400 to 700 nm, peaking around 436 nm. No significant differences in measurements between tumours and the corresponding control sites were found. A large spatial variation in the fluorescence intensity was observed both in the tumours and in the control sites. Standard deviations found ranged from 0.15 to 1.5 times the mean fluorescence. Fluorescence images, excited with 375 nm and taken with an image intensified CCD camera, on eight malignant melanomas and eight benign pigmented lesions did not indicate any fluorescence intensity distribution specific to the malignancy of the lesion. Neither the shape of the fluorescence spectra, nor the spatial distribution of the fluorescence intensity showed any signature specific to the histopathological nature of the lesions investigated. Optical diagnostics of skin tumours using the autofluorescence does not seem to be feasible at the present time.     

Combined mortality and morbidity of direct surgical treatment of abdominal aortic aneurysm

Two hundred aneurysms of the abdominal aorta were treated surgically from 1980 to 1987 by the same surgeon. There were 187 men and 13 women whose mean age was 66.1 years. Nine patients were 80-years-old or more. Eighty-seven percent of patients had preoperative risk factors, 30% of which were coronary artery disease. The operative approach was through a transverse laparotomy in 188 patients compared to 11 midline incisions and one lumbotomy. An aortoaortic tube was inserted in 87 patients, a bifurcated prosthesis in 99, and a tube bypass in 14. Five patients (2.5%) died within the 30 day perioperative period. Death was due to colonic necrosis, right heart chamber thrombosis, renal failure after repeat operation for acute lower limb ischemia, and myocardial infarction associated with renal and respiratory failure. The morbidity rate was 15.7% (31 patients) and included seven neurologic accidents, four respiratory complications, five ischemic events of the lower limbs requiring reoperation and one amputation, four cardiac complications, two renal failures, one reversible colonic ischemia, one revision for incomplete hemostasis, one phlebitis, one sliding syndrome, and five minor infections or cutaneous complications. Mean duration of hospital stay was 10.9 days. These results confirm that direct operation on aortic aneurysms can be performed in patients from all age groups and even with associated diseases. A rapid, simple technique based on a transverse approach, minimal dissection and insertion of aortoaortic tubes, whenever feasible, appears to reduce combined mortality-morbidity.Presented at the Annual Meeting of the Societé de Chirurgie Vasculaire de Langue Française, May 20–21, 1988, La Grande Motte, France.