The clinical diagnosis of Alzheimer's disease without the use of head imaging studies. A cliniconeuropathological study

Although head imaging studies are frequently used in the work-up of dementia, published criteria for the clinical diagnosis of Alzheimer's disease (AD) do not require them. Since our brain bank contains cases in which physicians had specifically diagnosed AD without using a head imaging study, we thought it of interest to investigate the accuracy of their clinical diagnoses. We retrospectively reviewed 911 consecutive dementia cases for those clinically diagnosed as either AD or senile dementia (SD). Twenty-one were identified in which head imaging studies had not been used, each diagnosed as AD or SD by a different physician. In only three had the physician reported a reason why a study was not done. In all 21 cases the primary neuropathological cause of the dementia was AD. Neuropathology in addition to AD was also noted, including cortical Lewy bodies in three, infarcts on gross examination in three, multiple microscopic infarcts in four, and multiple cerebral metastases in one. Acknowledging a number of study limitations, it is remarkable that the judgment of the physicians was correct regarding AD in all 21 cases. It is questionable if a head CT or MRI scan at time of diagnosis would have benefited any of the patients.     

Medical laboratory quality and accreditation in Jordan

ObjectivesTo investigate and describe the current status of quality regulations and accreditation standards in the medical laboratories in Jordan.Design and methodsDescribe the demography of Jordan. Classify the medical laboratories by health sectors. Describe the authority bodies in regard to health sectors and medical laboratories. Review the current by laws of licensing a medical laboratory, quality regulations, and accreditation projects currently active in Jordan.ResultsJordan is a developing country in the Middle East with limited resources, young population, but special success in education and health sectors. Medical laboratory services are being provided by many sectors. In regard to licensing to open a private laboratory, regulations are set and applied well. Regulations with regard to quality are set, but are not uniformly applied. Accreditation is a new concept, a voluntary process, and been granted to few laboratories by international accreditation bodies. Two local accreditation projects have started licensing to open a private laboratory is well regulated.ConclusionsQuality regulations are set, but not uniformly applied. Accreditation is a new concept and needs to be encouraged and improved.     

Plumbagin,a medicinal plant (Plumbago zeylanica)-derived 1,4-naphthoquinone,inhibits growth and metastasis of human prostate cancer PC-3M-luciferase cells in an orthotopic xenograft mouse model

We present here first time that Plumbagin (PL), a medicinal plant-derived 1,4-naphthoquinone, inhibits the growth and metastasis of human prostate cancer (PCa) cells in an orthotopic xenograft mouse model. In this study, human PCa PC-3M-luciferase cells (2 × 10⁶) were injected into the prostate of athymic nude mice. Three days post cell implantation, mice were treated with PL (2 mg/kg body wt. i.p. five days in a week) for 8 weeks. Growth and metastasis of PC-3M-luciferase cells was examined weekly by bioluminescence imaging of live mice. PL-treatment significantly (p = 0.0008) inhibited the growth of orthotopic xenograft tumors. Results demonstrated a significant inhibition of metastasis into liver (p = 0.037), but inhibition of metastasis into the lungs (p = 0.60) and lymph nodes (p = 0.27) was not observed to be significant. These results were further confirmed by histopathology of these organs. Results of histopathology demonstrated a significant inhibition of metastasis into lymph nodes (p = 0.034) and lungs (p = 0.028), and a trend to significance in liver (p = 0.075). None of the mice in the PL-treatment group showed PCa metastasis into the liver, but these mice had small metastasis foci into the lymph nodes and lungs. However, control mice had large metastatic foci into the lymph nodes, lungs, and liver. PL-caused inhibition of the growth and metastasis of PC-3M cells accompanies inhibition of the expression of: 1) PKCε, pStat3Tyr705, and pStat3Ser727, 2) Stat3 downstream target genes (survivin and Bcl_xL), 3) proliferative markers Ki-67 and PCNA, 4) metastatic marker MMP9, MMP2, and uPA, and 5) angiogenesis markers CD31 and VEGF. Taken together, these results suggest that PL inhibits tumor growth and metastasis of human PCa PC3-M-luciferase cells, which could be used as a therapeutic agent for the prevention and treatment of human PCa.     

A pilot study of a test for visual recognition memory in adults with moderate to severe intellectual disability

Objective assessment of memory functioning is an important part of evaluation for Dementia of Alzheimer Type (DAT). The revised Picture Recognition Memory Test (r-PRMT) is a test for visual recognition memory to assess memory functioning of persons with intellectual disabilities (ID), specifically targeting moderate to severe ID. A pilot study was performed to investigate whether the r-PRMT could differentiate DAT-related memory decline from pre-existing poor memory functioning of persons with moderate to severe ID. The r-PRMT scores were compared between 26 participants with DAT and moderate to severe ID and 33 controls with similar levels of ID. The results revealed that the controls with DS showed uniformly high scores in contrast to those with DAT on the r-PRMT and the score distributions of two groups were distinctly different with no overlap. On the other hand, the controls with non-DS etiologies scored much lower with a wider score spread, resulting in significant overlap with the score distribution of the participants with DAT. In conclusion, the r-PRMT may be effective in identifying persons with DAT among persons with moderate to severe ID from DS. However, the r-PRMT may result in a high false positive error rate in discriminating those with DAT among persons with moderate to severe ID from non-DS etiologies, if the judgment is based on a single point assessment.     

Intensive chemotherapy with combinations containing anthracyclines for refractory and relapsing multiple myeloma. Finnish Leukaemia Group

94 patients with refractory multiple myeloma were treated in a multicentre trial with combinations of cytotoxic drugs including anthracyclines. All were refractory to a 5-drug combination containing 3 alkylating agents, vincristine and methylprednisolone (MOCCA). With a combination of epirubicin and iphosphamide a 50% response was achieved in 9% of 22 patients. The response rate after schedule VAP (vincristine, doxorubicin and prednisolone) was 8% of 13 patients and that after schedule VAD (vincristine, doxorubicin and dexamethasone) 20% of 59 patients. The previous chemotherapy had lasted for less than 12 months in 13 cases from among all these patients, and 5 of these (38%) responded. In contrast, there were only 10 responders (12%) among the 81 patients with longer previous chemotherapy.     

Semi-quantitative assay of D antigen site density by flow cytometric analysis

Summary. This study describes the comparative measurement of D antigen site density using a fluorescent indirect antiglobulin test (FIAT) read by flow cytometry. The test results confirmed the continuum of D antigen strength from weakest D through to R₂R₂ and also allowed the majority of weak D samples to be adequately distinguished from D-negative samples.     

Interferon (IFN)-α Activation of Human Blood Mononuclear Cells In Vitro and In Vivo for Nitric Oxide Synthase (NOS) Type 2 mRNA and Protein Expression: Possible Relationship of Induced NOS2 to the Anti–Hepatitis C Effects of IFN-α In Vivo

Although researchers have noted high level activation of rodent mononuclear phagocytes for nitric oxide (NO) synthase type 2 (S2) expression and NO production with a variety of agents such as interferon (IFN) γ and endotoxin, it has been difficult to demonstrate activation of human mononuclear phagocytes. The purpose of this study was to determine if IFN-α serves as an activator in vitro and in vivo in humans. Treatment of normal monocytes or mononuclear cells in vitro with IFN-α caused a dose-dependent increase in monocyte NOS2 activity and NO production, and increased expression of NOS2 protein and mRNA expression. To determine if in vivo administration of IFN-α also modulated NOS2, we studied blood cells from patients with hepatitis C before and after IFN-α therapy. Untreated patients with chronic hepatitis C virus infection had levels of NOS activity and NOS2 antigen in freshly isolated mononuclear cells similar to those of healthy subjects, and they expressed minimal or no NOS2 mRNA. However, IFN-α treatment of patients with hepatitis C infection was associated with a significant elevation in mononuclear cell NOS activity, NOS2 antigen content, and NOS2 mRNA content. IFN-α–treated patients had significant decreases in levels of serum alanine aminotransferase and plasma hepatitis C mRNA. The degree of IFN-α–enhanced mononuclear cell NOS2 antigen content correlated significantly with the degree of reduction in serum alanine aminotransferase levels. Thus, IFN-α treatment of cells in vitro or administration of IFN-α to hepatitis C patients in vivo increases expression of mononuclear cell NOS2 mRNA expression, NOS activity, NOS2 antigen expression, and NO production. Since NO has been reported to have antiviral activity for a variety of viruses, we speculate that induced NO production may be related to the antiviral action(s) of IFN-α in hepatitis C infection.     

Guidelines for the use of fresh frozen plasma

Fresh frozen plasma should only be used to treat bleeding episodes or prepare patients for surgery in certain defined situations. Definite indications for the use of FFP: 1. Replacement of single coagulation factor deficiencies, where a specific or combined factor concentrate is unavailable. 2. Immediate reversal or warfarin effect. 3. Acute disseminated intravascular coagulation (DIC). 4. Thrombotic thrombocytopenic purpura (TTP). Conditional uses: FFP only indicated in the presence of bleeding and disturbed coagulation: 1. Massive transfusion. 2. Liver disease. 3. cardiopulmonary bypass surgery. 4. Special paediatric indications. No justification for the use of FFP: 1. Hypovolaemia. 2. Plasma exchange procedures. 3. 'Formula' replacement. 4. Nutritional support. 5. Treatment of immunodeficiency states.     

STRL33, A Novel Chemokine Receptor–like Protein, Functions as a Fusion Cofactor for Both Macrophage-tropic and T Cell Line–tropic HIV-1

The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for subgroups of CD4⁺ cells can be explained, at least partly, by the selective use of G protein–coupled receptors (GPCRs). We have identified a novel human gene, STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to chemokine receptors and to chemokine receptor–like orphan receptors. STRL33 is expressed in lymphoid tissues and activated T cells, and is induced in activated peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest, STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for fusion mediated by Envs from both T cell line–tropic and macrophage-tropic HIV-1 strains. STRL33-transfected Jurkat cell lines also supported enhanced productive infection with HIV-1 compared with control Jurkat cells. Despite the sequence similarities between STRL33 and chemokine receptors, STRL33-transfected cell lines did not respond to any in a panel of chemokines. Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection.     

Intraoperative angioedema induced by angiotensin II receptor blocker: a case report

Background

Angiotensin II receptor blockers are a class of antihypertensive agent that is developed to exclude the adverse effects of angiotensin converting enzyme inhibitors. However, as angiotensin II receptor blockers have begun to be more widely prescribed, cases of angiotensin II receptor blocker-induced angioedema have been reported. Rare cases of angioedema following surgery in patients using angiotensin converting enzyme inhibitors have been published.

Case presentation

A 38-year-old man with past history of hypertension was admitted for an elective lumbosacral spine surgery. He had been taking Valsartan 160 mg a day for the past 4 years.At the end of the surgical procedure and turning the patient into supine position, we noticed severe swelling in the neck and the face with.an edematous tongue, floor of the mouth, glottis, and supraglottic areas. A diagnosis of drug induced angioedema was made and intravenous dexamethasone, diphenhydramine and ranitidine were given. The patient remained intubated and was transferred to the intensive care unit. The valsartan was suspected to be the precipitating factor for the angioedema and was therefore discontinued.The swelling started to regress after 2 h, and resolved completely by the third day.

Conclusion

The precise mechanism of angiotensin II receptor blocker-induced angioedema is still unknown and should be thoroughly investigated. This report demonstrates a unique case of intraoperative angiotensin II receptor blocker-induced angioedema. Potential differential diagnoses of postoperative facial edema are discussed in detail, including the prolonged prone positioning for posterior spine surgery. Anesthesiologists should be aware of such rare, but potentially dangerous, perioperative adverse reaction that can occur with angiotensin II receptor blockers use.