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.     

Optical properties of Intralipid: a phantom medium for light propagation studies.

Intralipid is an intravenous nutrient consisting of an emulsion of phospholipid micelles and water. Because Intralipid is turbid and has no strong absorption bands in the visible region of the electromagnetic spectrum, and is readily available and relatively inexpensive, it is often used as a tissue simulating phantom medium in light dosimetry experiments. In order to assist investigators requiring a controllable medium that over a finite range of wavelengths is optically equivalent to tissue, we have compiled previously published values of the optical interaction coefficients of Intralipid, most of which were measured at a wavelength of 633 nm. We have extended the measurements of the absorption and reduced scattering coefficients from 460 to 690 nm and the total attenuation coefficient from 500 to 890 nm. These measurements show that, for stock 10% Intralipid, the absorption coefficient varies from 0.015 to 0.001 cm-1 between 460 and 690 nm, the reduced scattering coefficient varies from 92 to 50 cm-1 between 460 and 690 nm, the total attenuation coefficient varies from 575 to 150 cm-1 between 500 and 890 nm, and the average cosine of scatter varies from 0.87 to 0.82 between 460 and 690 nm. With these data, we discuss the design of an optically tissue-equivalent phantom consisting of Intralipid and black India ink.     

Postnephrectomy arteriovenous fistula of the renal pedicle treated with detachable balloons: A case report

A case of postnephrectomy arteriovenous fistula of the right renal pedicle is reported here. The diagnosis was confirmed by angiography, and successful treatment was achieved using detachable balloon.     

Effect of an education and activation programme on functional limitations and patient-perceived recovery in acute and sub-acute shoulder complaints – a randomised clinical trial

Background  

The education and activation programme (EAP) aims at coping with psychosocial determinants to prevent the development of chronic shoulder complaints (SCs). The effect of the EAP on functional limitations and patient-perceived recovery after 6 and 26 weeks is evaluated in a randomised clinical trial.     

Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.