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BACKGROUND Stroke has profound impacts on families. Often, family members, including stroke survivors and the person who takes up the role of the primary caregiver, would encounter demands on finances, rehabilitation arrangement, and even conflicts. Hence, a family-oriented intervention is expected to enable families to rebuild internal and external resources to achieve optimal rehabilitation and community reintegration. OBJECTIVE This study aims to describe a design of a two-tier family-oriented care management intervention for enhancing the family functioning and care capacity of the caregivers of stroke survivors. METHODS The two-tier care management intervention was guided by a standardized protocol conducted by trained professional care managers (first tier) with the support of trained volunteers (second tier), which lasted for 8-12 weeks. Participants were recruited through collaborating hospitals according to inclusion and exclusion criteria. In order to examine the effectiveness and cost-effectiveness of the two-tier care management intervention, a two-arm randomization multicenter study was designed, including an active comparison group, which was guided by a standardized protocol conducted by trained volunteers. Dyadic participants, including both stroke survivors and their primary caregivers for both groups, were invited to participate in a questionnaire survey using standardized and purposefully developed measures 3 times: before the intervention, immediately after the intervention, and 2 months after the intervention. The primary outcome was family functioning measured by the Family Role Performance Scale and Family Assessment Device-General Functioning Scale. The secondary outcomes included caregiving burden, depressive symptoms, care management strategies, and the incremental cost-effectiveness ratio. RESULTS Recruitment began in January 2017 and was completed at the end of April 2019. Data collection was completed at the end of March 2020. As of March 2020, enrollment has been completed (n=264 stroke caregivers). A total of 200 participants completed the baseline questionnaires. We aim to publish the results by mid-2021. CONCLUSIONS This study successfully developed a two-tier care management protocol that aims to enhance the family functioning of the caregivers of stroke survivors. Guided by a standardized protocol, this family-oriented two-tier intervention protocol was found to be feasible among Chinese families. CLINICALTRIAL ClinicalTrials.gov NCT03034330; https://ichgcp.net/clinical-trials-registry/NCT03034330 INTERNATIONAL REGISTERED REPORT RR1-10.2196/16703

Cutaneous Rosai-Dorfman disease in a male patient presented as a clinically malignant left breast mass. The intra-operative frozen section indicated a benign inflammatory lesion and a simple excision was performed. The disease was apparently limited to the skin and subcutis of the left breast with no lymph nodes or other organs involvement. While the lesion demonstrated the characteristic morphology of Rosai-Dorfman disease, the diagnosis of granulomatous mastitis, epithelioid sarcoma and other cutaneous xanthohistiocytic proliferations were considered. In the absence of lymphadenopathy, a high index of diagnostic awareness is required to recognize the uncommon, solitary cutaneous Rosai-Dorfman disease.

A case of oligomeganephronic renal hypoplasia is described. The patient presented in infancy with vomiting and diarrhoea and eventually developed progressive renal failure. Glomerular morphometry allowed definitive diagnosis and demonstrated a decrease in number and an increase in size of the glomeruli. Electron dense deposits seen on electron microscopy correlated with positive fluorescence for IgG and simulated overload glomerulitis.

Tissue levels of neutral O-alkylglycerolipids were measured in rat liver during the course of hepatocarcinogenesis produced by feeding diethylnitrosamine. Enzyme altered foci, not recognizable with conventional histological techniques, were shown to be present in specimens obtained after 3 or 6 weeks feeding the carcinogen. Frank hyperplastic nodules were present at 11 weeks and hepatocellular carcinoma were found in all rats at 18 weeks. At no point during the course of carcinogenesis did the liver show an increase in either-linked neutral glycerolipids, characteristic of animal tumours. On the contrary, lower levels of neutral O-alkylglycerolipids were found in tissues containing hyperplastic nodules or tumour.

Peripheral glomerular capillary walls were studied in 26 cases of IgA nephropathy by means of the transmission electron microscope. Ultrastructural abnormalities were identified in 11 cases (42%). Abnormalities of the glomerular basement membrane (GBM) were the most frequent change which consisted of localized thinning, lamination, irregular thickening, disruption, membranolysis and aneurysmal dilatation of the GBM. Subendothelial electron dense deposits were seen. Necrosis and detachment of the podocytes from the GBM were also encountered. The changes were correlated with the clinical findings at the time of diagnosis which showed a significant correlation of these peripheral glomerular capillary wall lesions with proteinuria. With light microscopy, crescents were significantly more frequently seen in the cases showing the ultrastructural capillary wall abnormalities than those without. This observation suggested that local peripheral glomerular capillary wall damage was an important factor in the pathogenesis of the extracapillary lesions in IgA nephropathy.

Peripheral blood T-lymphocyte subsets in 179 Chinese subjects were enumerated by an indirect immunoalkaline staining method done on ordinary blood smears. Absolute counts (X 10(9)/L) were 1.32 +/- 0.53 (T11), 0.73 +/- 0.31 (T4), 0.45 +/- 0.22 (T8) for males (n = 135) and 1.22 +/- 0.39 (T11), 0.69 +/- 0.20 (T4), 0.44 +/- 0.19 (T8) for females (n = 44). T4:T8 ratio for males and females were 1.79 and 1.58, respectively (0.05 less than P less than 0.10). Within-film area-to-area difference was 4.2 +/- 2.1% (n = 537 films). Interobserver discrepancy was 54 per 3,000 cells counted, or 1.8%. Film-to-film difference was 5.4 +/- 2.6% (30 pairs). T-lymphocyte subsets enumeration by immunostaining blood smears is a simple and reliable alternative to the immunofluorescence method. It avoids procedures that could artifactually affect lymphocyte subsets. The lower T4:T8 ratios revealed in this study could result because of technical reasons.

Glomeruli from 48 cases of glomerulonephritis (Gn) were isolated and studied by means of the scanning electron microscope (SEM). Overall glomerular loss due to processing was 2.4%. SEM of these isolated glomeruli showed good preservation of glomerular structure. Changes of the podocyte cell body and its foot processes were noted and correlated with light microscopic morphology. Individual podocyte necrosis, variable foot process fusion and cell body swelling were seen in IgA nephropathy. Podocyte degeneration with separation from the glomerular basement membrane was evident in idiopathic minimal change Gn while idiopathic membranous Gn was characterized by globular swelling of the podocyte cell bodies. In focal sclerosing Gn, large spherical bodies arising from swollen podocyte cell bodies were frequently encountered. Innumerable microvilli and small spherical bodies characterized membranoproliferative Gn. Variable podocyte cell body swelling, microvilli and small spherical bodies were seen in cases of lupus nephritis. Taken alone, none of the SEM changes were diagnostic. However, when the type of the change, the severity and the combination of the changes were considered as a whole, they were indicative of what light microscopy might reveal and helpful in differentiating between idiopathic minimal change Gn and focal sclerosing Gn.

By means of electron microscopy, three types of mesangial cell change were identified in IgA nephropathy. They represented proliferative, phagocytic and resting mesangial cells. The proliferative mesangial cells were characterised by the presence of centrioles, numerous free ribosomes, well developed Golgi apparatus and SER. They were found in the proliferative forms of IgA nephropathy. Phagocytic mesangial cells had numerous spinous cytoplasmic processes, better differentiated RER and numerous dense bodies and lipid inclusions. They were found in all histological forms of IgA nephropathy. The resting mesangial cells were unusual and were occasionally present in cases with normal numbers of mesangial cells.

The clinical course and biopsy findings of twenty-one patients with IgA nephropathy, followed up for a mean period of 37.4 mth (range 24-54 mth) after diagnosis, were reviewed retrospectively to determine whether the clinical presentations, the laboratory findings or histopathologic changes have prognostic implications. An age of 24 yr or above and a serum creatinine of 0.18 mmol/l or above at diagnosis correlated significantly with renal insufficiency at the end of the follow-up (P = 0.0230.03). Proteinuria of 1.5 g/d or more and hypertension (systolic greater than 150 mmHg or diastolic greater than 100 mmHg) when well controlled, were not found to be significant. Asymptomatic proteinuria and gross hematuria, on the other hand, correlated negatively with renal insufficiency at the end of the follow up (P = 0.034). With respect to histopathological changes, greater than 30% global glomerular sclerosis and moderate or marked tubular atrophy correlated significantly with renal insufficiency (P = 0.005 and 0.005). However, less than 10% glomerular crescents, small amounts of mesangial electron dense deposits or absent ultrastructural peripheral glomerular capillary wall abnormalities correlated negatively with renal insufficiency (P = 0.017, 0.030.03).

Environmental factors contributing to incidences of thyroid carcinoma are re-evaluated and emphasized in this study. Thyroid cancers appear to occur independent of endemic goiter, based on epidemiologic and histologic evidence. While environmental factors appear to be important, the specific etiologic agent has not yet been identified or suggested. The number of thyroid cancer incidences available from cancer registries are analyzed in an attempt to identify a specific environmental carcinogenic agent. The presence of active volcanoes that produce abundant lava is found to be the common denominator of lceland and Hawaii, where the incidence of thyroid cancer is outstandingly high. Comparison with other areas with active volcanoes is made. The presence of a carcinogenic agent in the lava is postulated and its possible mode of action on humans through fish products is hypothesized.

The clinical and autopsy findings in a premature baby who died of acute renal failure after therapy with gentamicin (5 mg/kg/day) and penicillin are presented. The serum gentamicin concentration had reached toxic levels when anuria developed. Numerous periodic acid Schiff (PAS) positive, diastase resistant cytoplasmic inclusion bodies which appeared as myelin figures in cytosegresomes under the electron microscope were identified in the proximal convoluted tubules. The pathological changes induced by gentamicin in the human neonatal kidneys have not been previously reported.

Administration of N-nitrosodimethylamine (NDMA) to zinc deficient rats intragastrically twice weekly for 8 weeks resulted in the development of forestomach tumors in 63% of treated animals. The tumors were frequently found at the junction between the fore and glandular stomach and were multiple. Smaller numbers of tumors were also present in the more proximal parts of the forestomach. All tumors were squamous papillomas. Similar tumors were not observed in zinc sufficient pair-fed rats given NDMA. These findings showed that NDMA, a non-esophageal and non-forestomach carcinogen in the rat, was tumorigenic in the presence of zinc deficiency.

A case of a peripheral lung tumour histologically categorized as a sclerosing hemangioma of the lung is presented. Ultrastructurally, the tumour is composed of a mixture of epithelial and mesenchymal elements in varying stages of differentiation. Type II pneumocytes are identified as one epithelial component, while primitive mesenchymal cells with a tendency to develop into pericytes are the predominant mesenchymal component. The tumour appears to differentiate along the line of the pulmonary alveolar septa, and should be designated as a 'pulmonary alveolar mixed tumour'.

A method for the preparation of human renal biopsy specimens for scanning electron microscopy (SEM) is described. This involves glomerular isolation by fine needle dissection and the simultaneous processing of 10 or more specimens in a specially designed tissue cassette. The method is simple and reliable with minimal glomerular loss during processing. Processed glomeruli appear intact under the SEM. They have clean surfaces with minimal extraneous deposits. Surface topography of the glomerulus is clearly seen and changes of the podocytes in glomerular diseases can be readily studied.

The influence of dimethylnitrosamine (NDMA), a liver carcinogen and nitrosobenzylmethylamine (NBMA) as esophageal carcinogen on [3H]thymidine incorporation into DNA was studied in the esophagus, liver, forestomach and gastric-stomach of fasted zinc-deficient and pair-fed zinc-sufficient rats, measured 1 h after the thymidine injection. In the untreated animals, dietary zinc deficiency significantly depressed [3H]thymidine incorporation (89%) into the DNA of forestomach only. NDMA, administered 4 h before death at 30 mg/kg, produced 50-55% inhibition in [3H]thymidine incorporation in the esophagus of rats of both dietary groups. This inhibition became more pronounced in the forestomach, reaching 90-94% in the zinc-deficient forestomach and 63-86% in their zinc-sufficient counterparts at NDMA levels ranging from 5 to 20 mg/kg. NBMA at 2 mg/kg produced 60% inhibition in the DNA synthesis of zinc-deficient esophagus and 40% in the corresponding zinc-sufficient ones, this difference being significant at P less than 0.01. On the other hand, [3H]thymidine incorporation in the forestomach DNA was markedly lowered in the presence of NBMA. Recovery of DNA synthesis in the 4 tissues from a single dose of NDMA or NBMA was monitored up to 12 days. Following NDMA injection, [3H]thymidine incorporation in the forestomach of both dietary groups remained inhibited (3% of untreated control) for 5 days, a significant recovery (45% of untreated control) was observed only in the zinc-sufficient animals. Following NBMA injection, [3H]thymidine incorporation was also inhibited in the zinc-deficient esophagus for a longer time than in the zinc-sufficient ones. In autoradiographic studies, the percentage of cells showing 30 or more grains/nucleus was significantly decreased (P less than 0.001) in the NBMA-treated and marginally decreased (P less than 0.05) in the NDMA- or NBMA-treated zinc-deficient and zinc-sufficient rats as compared with the saline-treated zinc-sufficient controls. These results were discussed in the light of our previous findings that NBMA enhanced esophageal tumorigenesis in the zinc-deficient rats and that NDMA, a liver carcinogen produced forestomach tumors in the zinc-deficient but not in the zinc-sufficient rats.

Renal biopsies of 44 Chinese patients with primary IgA glomerulonephritis (IgA Gn) were examined by light (LM), electron (EM) and immunofluorescent microscopy (IF). The diagnosis of IgA Gn was based on IF staining showing predominant mesangial IgA deposition in the absence of systemic diseases. With LM, IgA Gn was not essentially different from other idiopathic forms of glomerulonephritis. The glomerular lesions showed features of focal proliferative glomerulonephritis (45.4%), focal sclerosing glomerulonephritis (25%), minimal glomerular lesions (18.2%) and diffuse mesangial proliferative glomerulonephritis (11.4%). Membranous and membrano-proliferative forms were not encountered. The variable LM findings contrasted markedly with the constancy of IF staining. EM revealed lumpy electron dense deposits in the mesangium in all cases which, in the relative absence of subendothelial and subepithelial deposits, might also be helpful in diagnosis.

Histochemical studies of mucins were carried out on 17 autopsy specimens of cholangiocarcinomas associated with clonorchiasis. All tumours produced epithelial mucins which were mixtures of neutral and acid mucopolysaccharides without any histochemically demonstrable components of sialic and uronic acids. The mucins were qualitatively similar to that secreted by normal and Clonorchis-infested bile ducts. However carboxymucins were reduced and sulphomucins were absent or present only in trace amounts in the neoplastic epithelium; in the hyperplastic epithelium in clonorchiasis sulphomucins were abundant. The HID-AB technique for sulphomucins is valuable in differentiating hyperplastic bile ducts and cholangiocarcinoma.

A renal biopsy from a patient with lepromatous leprosy but no history of erythrema nodosum leprosum (ENL) showed histologic, immunofluorescent, and ultrastructural features typical of immune-complex glomerulonephritis. A literature review found reports of 187 renal biopsies from leprosy patients, with glomerulonephritis in 31% of the cases, and a variety of other renal lesions. This accumulated evidence demonstrates that, contrary to widely held opinion, there is no association between glomerulonephritis and a history of ENL. Furthermore, it suggests that glomerulonephritis in leprosy patients has a similar incidence in lepromatous and non-lepromatous cases. These observations have an important bearing on concepts regarding the pathogenesis of immune complex glomerulonephritis in leprosy and the humoral immune mechanisms in patients with leprosy.