Scintigraphic diagnosis of tricuspid regurgitation

The authors describe a simple technique for diagnosis of tricuspid regurgitation. Red blood cells were labeled in vivo with 99mTc and 22 patients were studied with ECG-gated blood-pool imaging of the liver. A single region of interest was manually drawn around the liver and a time-activity curve obtained. The per cent change in liver counts during the cardiac cycle was found to be significantly higher in the 12 patients with tricuspid regurgitation (Group I) (mean, 4.04 +/- 1.6%; range, 1.3-21.4%) compared with the 10 controls (Group II) (mean, 0.35 +/- 0.16%; range, 0.013-1.3%) (p less than 0.05). Using a 1% change in liver counts as the criterion of a positive study, all 12 cases in Group I were diagnosed correctly, but there was one false positive in Group II; thus the sensitivity was 100% and the specificity 90%.     

Should patients with a pre-operative prostatespecific antigen greater than 15ng/ml be offered radical prostatectomy?

Background Patients with prostate cancer with a pre-operative prostate-specific antigen (PSA) τ;15ng/ml who undergo radical retropubic prostatectomy (RRP) generally do not have a good outcome, yet may have organ-confined cancer and should be offered the option of surgery. Aim To assess the outcome of patients who underwent RRP with a pre-operative PSA ≥ 15ng/ml. Methods Thirty-four patients, mean pre-operative PSA: 25.46ng/ml (15.03–76.6) and mean Gleason score: 6.4 (5–9) were assessed. Results Two groups were identified. Group I: 41% (14/34) have no biochemical recurrence to mean follow up of 58 months (30–106). Mean PSA: 18.8ng/ml (15.03–25.84). Mean Gleason score: 6.1 (5–7). Clinical stage: T1c in 80%. No patient had seminal vesicle or lymph node involvement. Group II: 59% (20/34) have biochemical recurrence or died (3) from their disease to mean follow up of 66 months (36–98). Mean PSA: 28.9ng/ml (15.28–76.6). Mean Gleason score: 6.7 (5–9). Clinical stage: T1c in 25%. Eleven patients had seminal vesicle (8) involvement or positive lymph nodes (3) or both (2). Conclusion RRP seems feasible in patients whose pre-operative PSA is between 15 and 25ng/ml with stage T1c, Gleason score ≤ 7 and negative lymph node frozen section.     

Promiscuous beta-strand interactions and the conformational diseases

Conformational change plays an important role in the life of all proteins, starting from when they fold, through their function and often their fate. For an increasing number of proteins inappropriate conformational change leads to a chain of events, which culminate in the deposition of proteinacious aggregates and disease. In this review we consider the current literature on a number of proteins which form part of the Conformational Disease family. We describe here two types of aggregate that can be formed, Type I aggregates are typified by the Serpin superfamily and consist of non-fibrillar polymeric species. Type II aggregates are of the classical fibrillar form formed by a diverse range of proteins. Through biochemical and biophysical analysis of the aggregation reaction of members of these two classes we show that they form these aggregates through highly similar pathways. Essentially, the whole process can be summed up in two key stages. Firstly, the existence of conditions which increase the conformational flexibility of the protein, enabling it to adopt a partially folded state. Secondly, the propensity of this intermediate conformer to form intermolecular linkages leads to multimeric forms, a step often mediated via hydrophobic or beta -strand interactions. Our understanding of these structural changes has facilitated the rationale design of specific aggregation inhibitors. We will discuss the successes and pitfalls of such approaches to demonstrate how similar approaches may be applied to any misfolding protein.     

Radiotherapy in conjunction with intravenous infusion of 180 mg of disodium pamidronate in management of osteolytic metastases from breast cancer: clinical evaluation,biochemical markers,quality of life,and monitoring of recalcification using assessments of gray-level histogram in plain radiographs

PURPOSE: To evaluate the clinical improvement and radiographically monitor the effect of local radiotherapy in conjunction with disodium pamidronate (DP) on metastatic osteolytic disease. METHODS AND MATERIALS: Thirty-three patients with osteolytic metastasis from advanced breast cancer received radiotherapy with a 6-MV linear accelerator up to a dose of 30 Gy (3 Gy/fraction, 5 d/wk) combined with 24 monthly sessions of a 180-mg DP infusion. Conventional X-rays were obtained during the first six sessions of DP treatment, retaining the same settings for each exposure. The analysis of the image attributes was based on measuring the first-order statistics of the mean value and energy of gray-level histograms in the osteolytic region. RESULTS: The 6-month measurements compared with baseline showed statistically significant differences (p < 0.01, Wilcoxon test) in energy of gray-level histogram (-10.8%), mean value of gray-level histogram (+9.5%), pain score (-5.8 points), Eastern Cooperative Oncology Group status (-2.4 points), urine hydroxyproline/creatinine ratio (-41.7%), urine calcium/creatinine ratio (-58.8%), and bone alkaline phosphatase (-42.4%). Quality of life as determined by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (version 3) also improved. During follow-up, 88% of patients had complete and 12% partial responses (International Union Against Cancer radiologic criteria). On multivariate analysis, greater changes in the mean value of the gray-level histogram and negative nodal status were predictors for a reduction in the number of skeletal complications after therapy. Flu-like syndrome occurred in 13 patients (39%) and was well managed with mild antipyretics. CONCLUSION: Image-processing in plain radiographs offers an objective way to assess recalcification. The image-processing indexes, along with the measurements of performance status, quality of life, and biochemical markers, improved significantly. Local radiotherapy combined with long-term high-dose DP up to 180 mg is tolerable and has a high therapeutic response.     

Appendicitis During Pregnancy

Acute appendicitis is the most common extra-uterine surgical emergency requiring immediate surgical intervention during pregnancy [1]. Six young female patients presented with appendicitis during May 1996 to May 2001 in different service hospitals. Five patients underwent emergency appendectomy successfully. Gestational age at presentation included first trimester in 4 patients, second trimester in 2 patients and none in third trimester. 84% had pathologically proven acute appendicitis. One patient presented with appendicular lump in first trimester, proved on ultra sonography examination, which was treated by Oshner Sherren regime and subsequently interval appendectomy was done in second trimester. No long term adverse maternal morbidity or mortality was reported. One patient had premature onset of labour and delivered. Natural history of acute appendicitis is not changed during pregnancy while gestational physiological changes obscure the accurate diagnosis of acute appendicitis.Key Words: Acute appendicitis, Appendectomy, Pregnancy     

Opioid treatment for agitation in patients with advanced dementia

BACKGROUND: Some patients with advanced dementia cannot convey the experience of pain verbally and may react to pain with aggressive and agitated behaviors. We hypothesized that unrecognized pain could contribute to agitation and that low dose opioid therapy might reduce agitation by reducing pain. We therefore attempted to determine the effect of opioids on agitation in demented patients. METHODS: We administered placebo for 4 weeks and a long-acting opioid for another 4 weeks to nursing home patients with advanced dementia and severe agitation despite treatment with psychotropic drugs. Patients and study nurses did not know if the medication administered was placebo or opioid. We measured the Cohen-Mansfield Agitation Inventory (CMAI) score at baseline and every two weeks. RESULTS: Among 47 patients who entered the study, 25 completed the two phases. The median age for the 25 patients was 85.5 years. Analyses of the data of these 25 patients and of the patients <85 years-old showed no significant differences in agitation level between the placebo and opioid phases. However, among the 13 patients who completed the study and were > or =85 years old, the agitation level at the end of the opioid phase was significantly lower than at the end of the placebo phase (mean change in CMAI score: -6.4; 95% confidence interval (CI): -10.96, -1.8). The decrease in agitation in the patients > or =85 years old persisted after adjusting for sedation. The results remained unchanged when we expanded the analyses to include four > or =85 patients who dropped out of the study after the second week of the opioid phase. CONCLUSION: Low dose, long-acting opioids can lessen agitation that is difficult to control in very old (> or =85) patients with advanced dementia.     

Metalloproteinase inhibitors: new opportunities for the treatment of rheumatoid arthritis and osteoarthritis

The clinical efficacy of anti-TNF-alpha therapies have highlighted the apparently central role that TNF-alpha plays in the pathology of rheumatoid arthritis, particularly the inflammatory component. Recent identification of a metalloproteinase from the metzincin superfamily responsible for the production of the soluble form of this cytokine, has generated a large amount of pharmaceutical interest and presents the prospect of a metalloproteinase inhibitor as an anti-inflammatory drug. However, the traditional focus of metzincin inhibitor research has been the identification of inhibitors of matrix metalloproteinases; enzymes associated with matrix destruction, a feature common to both rheumatoid arthritis and osteoarthritis. Inhibitors of this class of metalloproteinase are now in clinical evaluation in patients. This review summarises the current development status of metalloproteinase inhibitors in arthritic diseases and discusses some of the issues that have arisen during their progress to become clinical treatments for these diseases.     

Obstetric and nonmalignant gynecologic bleeding: treatment with angiographic embolization

Eight patients (seven post partum, one post abortion) with massive pelvic hemorrhage related to pregnancy and one patient with uncontrollable bleeding following a cervical biopsy underwent angiography to facilitate the identification and treatment of bleeding sites. In all nine patients pelvic hemorrhage was successfully controlled with embolization under angiographic guidance. Angiographic embolization allowed preservation of the uterus in six patients referred prior to hysterectomy, and one patient subsequently became pregnant. When conservative measures and minor surgical repairs have failed, embolization should be the next step in the treatment of postpartum hemorrhage to avoid major surgery in an unstable patient and to maintain reproductive function.