Effectiveness of the “living successfully with low vision” self-management program: Results from a randomized controlled trial in Singaporeans with low vision

ObjectiveTo determine the effectiveness of the “Living Successfully with Low Vision” (LSLV) self-management program to improve patient-reported outcomes in Singaporeans.MethodsIn this randomized controlled trial, 165 participants with low vision (LV) were recruited and assigned to usual care (LV aid training only; N = 82) or LSLV program (N = 83). The LSLV program focuses on problem solving, coping mechanism and anticipation/preparation for future needs. The primary outcome was vision-related quality of life (VRQoL; measured using the Impact of Vision Impairment [IVI] questionnaire), while secondary outcomes included health-related quality of life; mental health; and self-efficacy, assessed at baseline, 2-weeks and 6-months post-intervention. Within- and between-group comparisons were conducted using paired t-tests and repeated measures analysis of covariance, respectively.ResultsA total of 128 individuals (77.6%) completed all assessments. At 2 weeks, LSLV participants alone experienced a significant within-group improvement in the mean IVI Emotional score (P = 0.05) but not at 6 months. No other within- or between-group effects were observed.ConclusionWhile SM programs have shown promising results in the management of many chronic diseases, our findings suggest that the LVSM program was not an effective approach for LV rehabilitation in Singapore.Practice implicationOther evidence-based strategies to improve QoL in patients with LV may be warranted.     

Clinicopathological characterization of so-called “cholangiocarcinoma with intraductal papillary growth” with respect to “intraductal papillary neoplasm of bile duct (IPNB)”

Cholangiocarcinoma (CC) of the biliary tract occasionally presents a predominant intraductal papillary growth in the bile ducts, called as biliary tract carcinoma (BTC) of papillary growth (PG) and intrahepatic CC (ICC) of intraductal growth (IG) type. Recently, intraductal papillary neoplasm of bile duct (IPNB) has been proposed as a pre-invasive biliary neoplasm. This study was performed to characterize pathologically BTC of PG type and ICC of IG type with respect to IPNB. It was found that 126 of such 154 CCs (81.8%) fulfilled the criteria of IPNB, while the remaining 28 cases showed different histologies, such as tubular adenocarcinoma and carcinosarcoma. These IPNBs occurred in old aged patients with a male predominance, and the left lobe was rather frequently affected in the liver. A majority of these cases were high grade IPNB (43 cases) and invasive IPNB (77 cases), while low grade IPNB was rare (6 cases). Pancreatobiliary type was predominant (48 cases) followed by gastric (30 cases), intestinal (29 cases) and oncocytic (19 cases) types. Mucus hypersecretion was found in 45 cases, and this was frequent in IPNB at the intrahepatic large bile duct and hilar bile ducts but rare at the extrahepatic bile ducts. Interestingly, 36 cases of high grade and invasive IPNBs contained foci of moderately differentiated adenocacinoma within the intraductal papillary tumor. In conclusion, a majority of ICC of IG type and BTC of PG type could be regarded as a IPNB lineage, and clinically detectable IPNBs were already a malignant papillary lesion.     

Mucinous cystic tumor with CK20 and CDX2 expression of the thymus: Is this a benign counterpart of adenocarcinoma of the thymus,enteric type?

Primary thymic adenocarcinoma is extremely rare. Moreover, thymic pure epithelial benign neoplasms are extremely rare. We encountered a cystic tumor almost purely composed of goblet cell‐like mucus‐producing cells of the thymus. A mass lesion of the mediastinum was detected in a 54‐year‐old man. The gross specimen presented a unilocular cystic lesion containing abundant mucin, measuring 8 × 5.5 × 4.5 cm. Microscopic examination revealed a cystic tumor consisting of bland mucus‐producing cells resembling goblet cells and forming tiny daughter cysts within the dense fibrous capsule. No destructive growth or infiltration into surrounding thymic tissue was observed. Papillary growth was found in a small focus. Immunohistochemically, tumor cells were positive for cytokeratin 20 and caudal type homobox 2, which are representative markers of enteric differentiation. The patient has been well without any recurrence for approximately ten years after the operation. Thus, the tumor should be regarded as a mucinous cystic tumor in the thymus. Very recently, thymic adenocarcinoma with enteric differentiation was proposed as a novel subtype of thymic carcinoma. This case could be regarded as a benign counterpart of adenocarcinoma of the thymus, enteric type. A further follow‐up study is required to confirm the exact biological behavior of this tumor.     

Effect of histamine on gastric acid secretion “in vitro”: Interference with endogenous prostaglandins

The interference between histamine and endogenous prostaglandins (PGs) was investigated in the isolated gastric fundus from immature rats by evaluating the effect of nonsteroidal antiinflammatory agents (NSAIDs) on the acid response to histamine and the effect of histamine on PGs production by the gastric mucosa. Indomethacin (10^–5 M) and diclofenac (10^–5 M) caused a dose-dependent enhancement of the response to histamine, dimaprit and DBcAMP, but did not affect bethanechol-, isoprenaline- and forskokin-induced acid production. The enhancing effect of indomethacin was abolished in low Ca²⁺ medium. PGE₂ and 6-keto PGF₁ levels in the mucosal solution were not modified by histamine, while being reduced by indomethacin. From these data it is concluded that endogenous PGs may negatively modulate the secretory response to histamine. However, a direct effect of the amine on cyclooxygenase to increase PGs synthesis seems to be excluded since histamine did not modify PGs levels in the mucosal solution.     

Biotin-rich intranuclear inclusions in morule-lacking adenocarcinoma of the gallbladder: a new category of “neoplastic/non-morular” lesions

Biotin-rich intranuclear inclusions, also called optically clear nuclei, are observed in various neoplastic and non-neoplastic lesions, including pregnancy-related endometrium and benign and malignant neoplasms with morular structures. A recent study reported that lesions with biotin-rich intranuclear inclusions can be classified as (non-neoplastic) pregnancy-related endometrial and as (neoplastic) morular category. In the present report, we describe two cases of well-differentiated adenocarcinoma of the gallbladder in which biotin-rich intranuclear inclusions were found without morular structures. Immunohistochemically, as reported previously, the intranuclear inclusions were positive for biotin and two biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase). Intranuclear expression of -catenin was also observed in neoplastic cells with and without intranuclear inclusion. We also detected a frame shift mutation of APC gene in one case but no mutation of -catenin gene in both cases. Although intranuclear expression of -catenin by mutation of APC gene might contribute to carcinogenesis in our cases, the relationships among intranuclear expressions of -catenin, biotin, biotin-binding enzymes and intranuclear inclusions remain unclear. Our cases are the first neoplastic lesions with biotin-rich intranuclear inclusions that lacked morular structures. We propose a new neoplastic/non-morular category for lesions with biotin-rich intranuclear inclusions.     

HIV-1 progression links with viral genetic variability and subtype,and patient’s HLA type: analysis of a Nairobi-Kenyan cohort

In a Nairobi-Kenyan cohort of 50 HIV-1 positive patients, we analysed the prevalence of HIV-1 subtypes and human leucocyte antigen (HLA) alleles. From this cohort, 33 patients were selected for the analysis of HIV-1 infection progression markers (i.e. CD4 cell counts and viral loads) and their association with HIV-1 genetic variability and subtype, and patient’s HLA type. HIV-1 gag genetic variability, analysed using bioinformatics tools, showed an inverse relationship with CD4 cell count whereas with viral load that relationship was direct. Certain HLA types and viral subtypes were also found to associate with patients’ viral load. Associations between disease parameters and the genetic makeup of the host and virus may be crucial in determining the outcome of HIV-1 infection.     

A cognitive analysis of an acquired dysgraphic patient with an “allographic” writing disorder

This study reports the writing performance of an Italian dysgraphic patient who produces many “allographic” errors in his handwriting, which involve the apparently uncontrollable mixing of upper- and lower-case forms (e.g. “bolva” written as BolVA). We describe the patient's writing errors (which also include letter-form errors and the production of superimposed letters) and offer an interpretation of his impaired performance within a slightly modified version of a functional model of the processes underlying normal handwriting. We suggest that the patient has impaired selection of appropriate allographic forms of letters and has an additional deficit in the spatial control of the execution of his writing strokes.     

5-year cost/benefit analysis of revision of failed unicompartmental knee replacements (UKRs); not “just” a primary total knee replacement (TKR)

BackgroundA number of studies suggest that one advantage of a unicompartmental knee replacement (UKR) is ease of revision to a total knee replacement (TKR). We aimed to perform a cost/benefit analysis of patients undergoing this procedure at our centre to evaluate its economic viability.MethodsFrom our own prospective joint replacement database we identified 812 consecutive tibio-femoral UKRs performed (1994–2007) of which 23 were revised to TKR (2005–2008). These were then matched to a cohort of primary TKRs (42 patients). Data were collected regarding patient demographics, cost of surgery, clinical outcome (OKS) and follow-up costs at five years.ResultsThere was no significant difference in implant costs or in length of stay, however tourniquet time was significantly higher in the revision group (average 93 min (UKR) vs 75 min (TKR) p < 0.0001).At five years there was no significant difference in clinical outcome between the revision UKR and primary TKR groups, mean OKS 27 and 32 respectively (p = 0.20). The revision group had a greater complication and revision rate, attending significantly more follow-up appointments (average 6 (UKR) vs 2 (TKR) p < 0.0001) and consultant appointments (average 4 (UKR) vs 0.4 (TKR) p < 0.0001). This was translated to significantly higher follow-up costs.ConclusionRevision of UKR to TKR is not universally a straightforward procedure comparable to a standard primary replacement. Despite cost of components not being significantly higher than primary TKR there are multiple hidden follow-up costs. The clinical outcomes are however similar at 5 years.     

Let's not push the “panic” button: A critical analysis of panic and panic disorder in adolescents

Although recently published research has suggested the widespread prevalence of panic and panic disorder in older children and adolescents, several methodological considerations must be noted. A review of the studies of preadult panic reveals problems of internal and external validity, including small sample sizes, unreliable assessment procedures, restricted settings and sources of information, lack of assessment of panic severity, and lack of normative data. Although recent research has provided new and tantalizing information, it is suggested that definitive conclusions from the available data about panic prevalence in the general and clinical populations are not yet warranted. It is recommended that more cautious inferences should be made given the extant data, while future research should concentrate on amending existing methodological flaws. Implications for psychological theories of panic are also discussed.     

Immunohistochemical analysis of various serum proteins in living mouse thymus with “in vivo cryotechnique”

It has been difficult to clarify the precise localizations of soluble serum proteins in thymic tissues of living animals with conventional immersion- or perfusion-fixation followed by alcohol dehydration owing to ischemia and anoxia. In this study, ??in vivo cryotechnique?? (IVCT) followed by freeze-substitution fixation was performed to examine the thymic structures of living mice and immunolocalizations of intrinsic or extrinsic serum proteins, which were albumin, immunoglobulin G1 (IgG1), IgA, and IgM, as well as intravenously injected bovine serum albumin (BSA). Mouse albumin was more clearly immunolocalized in blood vessels and interstitial matrices of the thymic cortex than in tissues prepared by the conventional methods. The immunoreactivities of albumin and IgG1 were stronger than those of IgA and IgM in the interstitium of subcapsular cortex. The injected BSA was time-dependently immunolocalized in blood vessels and the interstitium of corticomedullary areas at 3.5 h after its injection, and then gradually diffused into the interstitium of the whole cortex at 6 h and 12 h. Thus, IVCT revealed definite immunolocalizations of serum albumin and IgG1 in the interstitium of thymus of living mice, indicating different accessibility of serum proteins from the corticomedullary areas, not from the subcapsular cortex of living animals, depending on various molecular sizes and concentrations.     

“That's a good question”: University researchers' views on ownership and retention of human genetic specimens

PurposeTo explore the views of university-based investigators conducting genetic research with human specimens regarding ownership and retention of specimens, and knowledge of related institutional review board and university policies.MethodsData were collected in three phases: a qualitative pilot study of 14 investigators; a web-based survey taken by 80 investigators; and follow-up, in-depth interviews with 12 survey respondents.ResultsInvestigators named a variety of single or multiple owners of human specimens and often expressed confusion regarding specimen ownership. Most associated ownership with rights to control, and responsibilities to maintain, specimens. Investigators viewed specimens as “precious” resources whose value could be increased through long-term or infinite retention, particularly in light of anticipated technological advances in genome science. Their views on ownership and retention were shaped by perceptions of institutional review board policies as immortalized in subject informed consent documents, rather than knowledge of actual policies.ConclusionLong-term retention of human specimens makes confusion about ownership particularly problematic. Given findings that investigators' views on ownership and retention are largely guided by their perception of university policies, the need for clear, consistent policies at the institution level is urgent.     

Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between “precursor-like” and “regular type” lesions

Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically “regular type” IDC-P and “precursor-like” IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.     

“Well,good luck with that”: reactions to learning of increased genetic risk for Alzheimer disease

PurposeApolipoprotein-E (APOE) genetic testing to estimate risk for developing late-onset Alzheimer disease is increasingly being offered without prior genetic counseling or preparation. Consumer interest continues to grow, raising the question of how best to conduct such testing.MethodsTwenty-six semistructured interviews were carried out to study the reactions of individuals who had already learned of their higher risk after APOE testing had been done because of a family history of Alzheimer disease, or from genetic tests done for other health-related or general-interest reasons.ResultsAdverse psychological reactions were reported by a substantial fraction of the participants, including those who had specifically sought testing, those for whom the information came as a surprise, those with a family history, and those with no known history. Still, nearly all of those interviewed said that they had benefited in the long term from lifestyle changes, often learned from online sources, that they subsequently made.ConclusionThe results show that people should be prepared prior to any genetic testing and allowed to opt out of particular tests. If testing is carried out and a higher risk is revealed, they should be actively assisted in deciding how to proceed.     

The direct effects of stored blood products may worsen prognosis of cancer patients; shall we transfuse or not? An explanation of the adverse oncological consequences of blood product transfusion with a testable hypothesis driven experimental research protocol

Francis and colleagues reported an association between blood transfusion and worsened cancer prognosis. Since then there has been much debate over whether there is in fact such an association. We propose a possible mechanism which could explain much of the conflicting clinical and experimental evidence, and which can be readily tested experimentally. It is suggested that the extracellular accumulation of bioactive factors in blood transfusion products can directly and indirectly cause tumour growth and hence a worsening of prognosis. This theory can be applied both in vitro and in vivo. Two separate UK studies have shown that perioperative blood transfusion is associated with worsened prognosis in head and neck squamous cell cancer patients. Furthermore, pilot experiments have shown that as blood ages, endothelial growth factors are leached from the metabolically compromised red cell. We believe that we have provided a rationale to explain the conflicting findings of research to date in this area. That red cells should store endothelial reparative growth factors would seem logical, as would the release of any factors as the metabolic processes of the anucleate red cell decline over time. As a result, leuco-depletion should be promoted and blood transfusion should be avoided if possible.