Supervised drug administration in patients with refractory hypertension unmasking noncompliance

Noncompliance with medication is common, particularly in asymptomatic conditions such as hypertension that require long-term treatment, and is often unsuspected. We describe two patients with refractory hypertension in whom noncompliance was confirmed by a precipitous fall in blood pressure when antihypertensive medications were given under direct supervision.     

Adenocarcinoma combined with malignant peripheral nerve sheath tumor of the gallbladder

Adenocarcinoma of the gallbladder combined with a malignant peripheral nerve sheath tumor (MPNST) in the gallbladder in an 81-year-old woman is reported. The resected gallbladder showed two distinct tumor components, the epithelioid type of MPNST and adenocarcinoma with areas of mucin production. Although the immediate postoperative course was uneventful, a pathologic fracture of her right upper femur developed 4 months after the cholecystectomy. The pathology was determined to be a feature of metastatic MPNST rather than of adenocarcinoma. A whole body bone scan revealed multiple metastases, including the left parietal skull, left ninth rib, seventh thoracic vertebra, and right upper third of the femur. Despite cholecystectomy and postoperative irradiation therapy, she died 6 months after diagnosis of the tumor. Without an autopsy the primary site of the MPNST was unknown. We found that the prognosis was very poor in patients with distal metastatic MPNST, especially in older patients.     

Evidence that mechanisms dependent and independent of nitric oxide mediate endothelium-dependent relaxation to bradykinin in human small resistance-like coronary arteries

1. The effects of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (L-NOARG), the NO scavenger, oxyhaemoglobin (HbO) and high extracellular K+ upon endothelium-dependent relaxation to bradykinin were investigated in human isolated small coronary arteries. 2. Endothelium-dependent relaxations to bradykinin were compared in vessels contracted to approximately 50% of their maximum contraction to 124 mM KCl Krebs solution, regardless of treatments, with the thromboxane A2 mimetic, U46619 and acetylcholine. All relaxations were expressed as percentage reversal of the initial level of active force. 3. L-NOARG (100 microM) caused a small but significant, 12% (P < 0.01), decrease in the maximum relaxation (Rmax: 91.5 +/- 5.4%) to bradykinin but did not significantly affect the sensitivity (pEC50: 8.08 +/- 0.17). Increasing the concentration of L-NOARG to 300 microM had no further effect on the pEC50 or Rmax to bradykinin. HbO (20 microM) and a combination of HbO (20 microM) and L-NOARG (100 microM) reduced Rmax to bradykinin by 58% (P < 0.05) and 54% (P < 0.05), respectively. HbO (20 microM) and L-NOARG (100 microM, combined but not HbO (20 microM) alone, caused a significant 11 fold (P < 0.05) decrease in sensitivity to bradykinin. HbO (20 microM) decreased the sensitivity to the endothelium-independent NO donor, S-nitroso-N-acetylpenicillamine (SNAP), approximately 17 fold (P < 0.05). 4. Raising the extracellular concentration of K+ isotonically to 30 mM, reduced the Rmax to bradykinin from 96.6 +/- 3.1% to 43.9 +/- 10.1% (P < 0.01) with no significant change in sensitivity. A combination of HbO, L-NOARG and high K+ (30 mM) abolished the response to bradykinin. High K+ did not change either the sensitivity or maximum relaxation to SNAP. 5. In conclusion, L-NOARG does not completely inhibit endothelial cell NO synthesis in human isolated small coronary arteries. By comparison, HbO appeared to block all the effects of NO in this tissue and revealed that most of the relaxation to bradykinin was due to NO. The non-NO -dependent relaxation to bradykinin in the human isolated small coronary arteries appeared to be mediated by a K(+)-sensitive vasodilator mechanism, possibly endothelium-derived hyperpolarizing factor (EDHF).     

Contemporary percutaneous treatment of unprotected left main coronary stenoses: initial results from a multicenter registry analysis 1994-1996

BACKGROUND: Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the results of percutaneous intervention may now approach those of CABG. METHODS AND RESULTS: To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15+/-8 months. Results varied considerably, depending on presentation and treatment. For patients with acute myocardial infarction, technical success was achieved in 75%, and survival to hospital discharge was 31%. For elective patients, technical success was achieved in 98.9%, and in-hospital survival was strongly correlated with left ventricular ejection fraction (P=.003). Longer-term event (death, infarction, or bypass surgery) -free survival was correlated with ejection fraction (P<.001) and was inversely related to presentation with progressive or rest angina (P<.001). Surgical candidates with ejection fractions > or = 40% had an in-hospital survival of 98% and a 9-month event-free survival of 86+/-5%, whereas patients with ejection fractions < 40% had 67% and 22+/-12% in-hospital and 9-month event-free survivals, respectively. Nine hospital survivors (10.6%) experienced cardiac death within 6 months of hospital discharge. CONCLUSIONS: While results for selected patients appear promising, until early post-hospital discharge cardiac death can be better understood and minimized, percutaneous revascularization of ULMT stenosis should not be considered an alternative to bypass surgery for most patients. When percutaneous revascularization of ULMT is required, directional atherectomy and stenting appear to be the preferred techniques, and follow-up angiography 6 to 8 weeks after treatment is probably advisable.     

Systemic arterial blood pressure and urine protein/creatinine ratio in dogs with hyperadrenocorticism

OBJECTIVE: To determine prevalence and severity of systemic arterial hypertension and proteinuria in dogs with naturally developing hyperadrenocorticism and to determine whether these abnormalities resolve with adequate management of the disease. DESIGN: Case series and cohort study. ANIMALS: 77 dogs with naturally developing hyper-adrenocorticism examined once; 15 dogs examined before and after treatment. RESULTS: Among dogs examined only once, hypertension was diagnosed in 21 of 26 dogs with untreated pituitary-dependent hyperadrenocorticism (PDH), 17 of 21 with inadequately controlled PDH, 8 of 16 with well-controlled PDH, 10 of 10 with an untreated adrenocortical tumor, and 0 of 4 that had undergone adrenalectomy because of an adrenocortical tumor. Untreated dogs and dogs with inadequately controlled PDH had significantly higher blood pressures than did other dogs. Proteinuria was documented in 12 of 26 dogs with untreated PDH, 5 of 16 with inadequately controlled PDH, 3 of 14 with well-controlled PDH, 5 of 8 with an untreated adrenocortical tumor, and 1 of 3 that had undergone adrenalectomy. Dogs with untreated PDH and dogs with an untreated adrenocortical tumor had higher urine protein/creatinine ratios than did dogs with well-controlled PDH. Among dogs evaluated before and after treatment, blood pressure and urine protein/creatinine ratio did not change in 8 dogs with inadequately controlled hyperadrenocorticism, but decreased in 7 dogs with well-controlled disease. CLINICAL IMPLICATIONS: Results suggest that systemic hypertension and proteinuria are common in dogs with untreated hyperadrenocorticism and that successful treatment of hyperadrenocorticism will result in resolution of these abnormalities in many, but not all, dogs.     

Screening instruments for depression and anxiety following stroke: experience in the Perth community stroke study

Evaluation of the relative efficacy of three screening instruments for depression and anxiety in a group of stroke patients was undertaken as part of the Perth community stroke study. Data are presented on the sensitivity and specificity of the Hospital Anxiety and Depression Scale (HAPS), the Geriatric Depression Scale and the General Health Questionnaire (GHQ) (28-item version) in screening patients 4 months after stroke for depressive and anxiety disorders diagnosed according to DSM-III criteria. The GHQ-28 and GDS but not the HADS depression, were shown to be satisfactory screening instruments for depression, with the GHQ-28 having an overall superiority. The performance of all 3 scales for screening post-stroke anxiety disorders was less satisfactory. The HADS anxiety had the best level of sensitivity, but the specificity and positive predictive values were low and the misclassification rate high.     

Cloning and characterization of cDNAs encoding S-RNases from almond (Prunus dulcis): primary structural features and sequence diversity of the S-RNases in Rosaceae

The ability of histamine H3 receptor ligands to interact with 5-HT3 receptors in NG108-15 cells was studied using the whole cell patch clamp recording technique. Imetit, a histamine H3 receptor agonist, generated inward currents and exhibited weak partial agonist activity at the 5-HT3 receptor (EC50 = 11.8 microM). Imetit-induced currents were slow to desensitize and at a high concentration reduced in size. The histamine H3 receptor antagonists iodophenpropit and thioperamide did not generate inward currents but were able to inhibit 5-hydroxytryptamine (5-HT) responses with an IC50 of 1.57+/-0.3 microM and 13.7+/-3.5 microM, respectively. Thioperamide is probably a non-competitive antagonist which may have more than one binding site on the receptor.     

Lipid hydroperoxides induce apoptosis in T cells displaying a HIV-associated glutathione peroxidase deficiency

8E5 is a chronically human immunodeficiency virus (HIV)-infected human T cell line, which we have previously shown to be extremely susceptible to hydrogen peroxide (H2O2)-induced apoptosis due to a HIV-associated catalase deficiency. Here we report that HIV gene expression additionally renders 8E5 cells 10-fold more sensitive than either uninfected A3.01 cells or HIV-infected but nonexpressing 8E5L cells to killing by 15-hydroperoxyeicosatetraenoic acid (15-HPETE), as well as several other hydroperoxy fatty acids. Whereas the viability of A3.01 and 8E5L cells was relatively unaffected by exposure to 10 microM 15-HPETE, similarly treated 8E5 cells underwent apoptosis, as demonstrated by morphological changes and the presence of fragmented DNA. The unique susceptibility of 8E5 cells was attributable to their inability to convert 15-HPETE to 15-hydroxy-eicosatetraenoic acid (15-HETE) owing to a marked reduction in glutathione peroxidase activity. Since oxidized lipids have been reported to accumulate in oxidatively stressed, HIV-infected individuals, a HIV-associated glutathione peroxidase deficiency may contribute to the depletion of CD4 T cells that occurs in the acquired immune deficiency syndrome (AIDS).