Standardizing the intensity of upper limb treatment in rehabilitation medicine.

OBJECTIVE: To describe a treatment protocol for the upper limb that standardizes intensity of therapy input regardless of the severity of presentation. DESIGN: The protocol is described (Part 1) and feasibility and effect explored (Part 2). SUBJECTS: Participants (n = 11) had a single ischaemic stroke in the middle cerebral artery territory more than one year previously, and had residual weakness of the hand with some extension present at the wrist and the ability to grasp. INTERVENTIONS: Following two baseline assessments, participants attended therapy for 1 hour a day for 10 consecutive working days. Treatment consisted of a combination of strength and functional task training. Outcomes were measured immediately after training, at one month and three months. OUTCOME MEASURES: Intensity was measured with Borg Rating of Perceived Exertion. Secondary outcome measures included Action Research Arm Test (ARAT), nine-hole peg test, and Goal Attainment Scale. RESULTS: Borg scores indicated that the level of intensity was appropriate and similar across all participants despite individual differences in the severity of their initial presentation (median (interquartile range) = 14 (13-15)). The mean ARAT score significantly increased by 6.8 points (chi(2)(3) = 15.618, P<0.001), and was maintained at three-month follow-up (z = - 2.384, P = 0.016). The nine-hole peg test also showed a main effect of time and 88% of goals set were achieved. CONCLUSIONS: The physiotherapy protocol standardized intensity of treatment by grading exercise and task-related practice according to the person's residual ability, rather than simply standardizing treatment times. It was feasible and well tolerated in this group.

Demonstration of fibrin in early stages of experimental metastases.

Tumor emboli were produced in lungs of Sprague-Dawley rats by i.v. injection of Walker 256 tumor cells into the tail vein. Tissues were examined by electron microscopy at periods from 30 sec to 72 hr after tumor injection. Two methods of conventional staining were used, in addition to immunoperoxidase techniques, with antifibrin antibodies produced in rabbits. Tumor cells accompanied by a platelet mass were seen in pulmonary arterioles at the earliest time period (30 sec). By conventional staining, small amounts of fibrin were detected within the platelet clumps by 5 min after inoculation. Periodicity indicating stable fibrin was not seen by this technique until 15 to 45 min. When peroxidase-labeled antibody was applied to tissue, sections showed fibrin-positive material at 30 sec, and periodicity of fibrin was detected by 5 min. Fibrin reached a maximum by both techniques at about 1 hr and disappeared, along with the platelets, at about 9 hr. When fibrinolysin was injected prior to the tumor cell inoculation, platelets and fibrin were either absent or present only in traces, and no stable fibrin was detected. These observations show that fibrin occurs very early in small amounts in association with tumor cell emboli, and is removed while the cells are still intravascular.

TESS: a geometric hashing algorithm for deriving 3D coordinate templates for searching structural databases. Application to enzyme active sites.

It is well established that sequence templates such as those in the PROSITE and PRINTS databases are powerful tools for predicting the biological function and tertiary structure for newly derived protein sequences. The number of X-ray and NMR protein structures is increasing rapidly and it is apparent that a 3D equivalent of the sequence templates is needed. Here, we describe an algorithm called TESS that automatically derives 3D templates from structures deposited in the Brookhaven Protein Data Bank. While a new sequence can be searched for sequence patterns, a new structure can be scanned against these 3D templates to identify functional sites. As examples, 3D templates are derived for enzymes with an O-His-O "catalytic triad" and for the ribonucleases and lysozymes. When these 3D templates are applied to a large data set of nonidentical proteins, several interesting hits are located. This suggests that the development of a 3D template database may help to identify the function of new protein structures, if unknown, as well as to design proteins with specific functions.

Derivation of 3D coordinate templates for searching structural databases: application to Ser-His-Asp catalytic triads in the serine proteinases and lipases.

It is well established that sequence templates (e.g., PROSITE) and databases are powerful tools for identifying biological function and tertiary structure for an unknown protein sequence. Here we describe a method for automatically deriving 3D templates from the protein structures deposited in the Brookhaven Protein Data Bank. As an example, we describe a template derived for the Ser-His-Asp catalytic triad found in the serine proteases and triacylglycerol lipases. We find that the resultant template provides a highly selective tool for automatically differentiating between catalytic and noncatalytic Ser-His-Asp associations. When applied to nonproteolytic proteins, the template picks out two "non-esterase" catalytic triads that may be of biological relevance. This suggests that the development of databases of 3D templates, such as those that currently exist for protein sequence templates, will help identify the functions of new protein structures as they are determined and pinpoint their functionally important regions.

Primary acute renal failure ("acute tubular necrosis") in the transplanted kidney: morphology and pathogenesis.

"Acute tubular necrosis" (ATN) in the transplanted kidney, when properly differentiated from other causes of acute renal failure, appears to be a relatively benign condition. It has been widely assumed to be pathologically identical to ATN in the native kidney, but its histopathologic features have not been studied in detail. Because immunosuppressive therapy with cyclosporine adds an additional layer of complexity to the morphologic changes observed, in the present study we have confined our observations to patients immunosuppressed with steroids and azathioprine. Thirteen renal allograft biopsies from patients with ATN and 5 biopsies from patients with normal allograft function were compared with the previously obtained series of 57 native kidney ATN biopsies and 20 control biopsies. Both qualitative and quantitative differences between transplant and native kidney ATN were found. Compared with native kidney ATN, transplant ATN showed significantly less thinning and absence of proximal tubular brush border and less variation in size and shape of cells in individual tubular cross-sections. There were also significantly fewer casts and less dilatation of Bowman's space and a significantly greater number of polarizable crystals presumed to be oxalate in transplant ATN. In native kidney ATN the tubular injury sites were mostly characterized by desquamation of individual epithelial cells leaving areas of bare basement membrane (the "non-replacement" phenomenon). In transplant ATN, sites of tubular injury, although rare and affecting only short tubular segments, were characterized by the actual presence of identifiable necrotic tubular cells, a finding seldom seen in native kidney ATN. There also was a greater interstitial infiltrate of mononuclear inflammatory cells in transplant ATN compared to native kidney ATN. Electron microscopic studies of 9 transplant ATN biopsies showed a mild reduction in proximal tubular brush border compared with controls but this alteration was significantly less than that observed in native kidney ATN. There was no significant alteration in proximal or distal basolateral infoldings and this contrasted sharply with the marked reduction in basolateral infoldings of the plasma membrane observed in native kidney ATN. Disintegrated necrotic cells were found by electron microscopy in transplant ATN whereas these were not observed in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. On the other hand, there were significantly greater numbers of "non-replacement" sites in the distal tubules in native kidney ATN compared to transplant ATN.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of Lipiodol and evidence for tumor necrosis in hepatocellular carcinoma.

To study the distribution and thromboembolic effect of Ultrafluid Lipiodol, 15 surgically removed hepatocellular carcinomas with selective intraarterial Lipiodol injection 7 to 10 days before surgery and 15 noninjected controls were studied radiologically and histologically. Tissue blocks were processed with an en bloc silver impregnation technique for Lipiodol localization in histologic sections. Lipiodol was distributed evenly in tumors measuring less than 5 cm in diameter and peripherally in tumors measuring 10 cm or more. Lipiodol droplets were mainly extracellular. There was no difference in tumor architecture or in hemorrhage and necrosis scores between Lipiodol-injected cases and negative controls (1.18 versus 0.92). Similarly, in injected cases, no differences were observed between Lipiodol-positive and Lipiodol-negative areas (scores of x-ray Lipiodol-positive versus Lipiodol-negative areas: 1.17 versus 1.36; scores of microscopic Lipiodol-positive versus Lipiodol-negative areas: 1.18 versus 1.14). Lipiodol-negative but hypodense areas examined by x-ray proved to be necrosis or fibrosis with or without viable tumor islands. Lipiodol has no thromboembolic effects. The uneven Lipiodol distribution may account for its failure as a carrier for chemotherapeutic agents in large tumors.

Demonstration of Lipiodol in paraffin sections using a modified silver impregnation technique.

To demonstrate postangiographic Lipiodol (LIP) in hepatocellular carcinoma (HCC) in paraffin sections, direct impregnation of formalin-fixed tissue blocks with silver nitrate (AgNO3) was followed by routine processing. LIP appeared as black globules in the sinusoids. Ninety-four tissue blocks from 13 postangiographic LIP HCCs and 69 from 8 non-LIP HCCs and 4 fatty livers were studied. Seventy-two of 73 negative controls and all positive blocks as seen on soft tissue radiographs (STRs) were correctly coded (specificity 98.6%, sensitivity 100%). Twenty-six of the 44 LIP-negative areas on STRs from LIP cases contained scanty globules of less than 10 microns in diameter. Fatty change gave no positive readings. Thus, modified AgNO3 impregnation is a simple, accurate means of detecting LIP in high-quality paraffin sections suitable for tumor diagnosis and, if applied to postangiographic LIP, ultrasonographically guided liver biopsy, can verify that a biopsy has reached a suspected tumor focus.

Invasion of the hepatic capsule by tumour metastases to the liver.

Liver metastases of Waler 256 tumour in rats and of C3HBA tumour in mice were produced by mesenteric vein inoculation of tumour suspensions. Gross liver nodules were examined by light microscopy and by transmission and scanning electron microscopy. Subcapsular tumour nodules were seen to penetrate the hepatic capsule in all animals and to lodge on the peritoneal surface. Penetration occurred by stretching and attrition of the thin hepatic capsule in these animals. Studies done on human hepatic metastases revealed a different picture. In only a small number of such cases did peritoneal involvement occur from subcapsular nodules, and in these the penetration was limited, apparently by way of capsular veins and lymphatics. The thick fibrous capsule of human liver appears thus to form a barrier to peritoneal tumour dissemination.

Multicentric reticulohistiocytosis: a report of a case and a review of the pathology.

A case of multicentric reticulohistiocytosis (MR) in a 24-yr-old woman is presented. MR is a rare disorder characterized by progressive polyarthropathy and a papulo-nodular skin rash. The diagnosis was established by histological examination of biopsies of erythematous nodules on the fingers which showed circumscribed collections of large mononuclear cells and multinucleate giant cells in the reticular dermis. These were embedded in a fine network of mature fibrous tissue with a scanty lymphocytic infiltrate. Histochemical, immunopathological and ultrastructural investigations confirmed that the large mononuclear cells had the properties of macrophages. The histopathological features of MR are reviewed in the light of current knowledge of macrophage physiology, and evidence for lymphocyte-histiocyte interactions in the pathogenesis of this bizarre granulomatous disorder is presented.

IgA nephropathy in relapsing polychondritis.

Relapsing polychondritis (RP) is a multisystem autoimmune disease characterized by the presence of antibodies to type II collagen. This collagen is found predominantly in cartilaginous tissues, vitreous humor, aorta and notochord. Involvement of the kidney is rare, only 7 cases having been recorded, and there is no type II collagen in glomeruli. Six of the previous cases had crescentic glomerulonephritis. We report here two cases of biopsy proven RP in which IgA nephropathy was seen, the first examples recorded. Both patients had hematuria and slight proteinuria, with mild impairment of renal function. The histological and immunofluorescence pattern on both biopsies was in keeping with IgA nephropathy. Both patients received steroids with diminution/disappearance of hematuria and proteinuria. In view of the potentially progressive nature of glomerular disease with RP, the renal status should be investigated in all patients with RP.

Immune response to transplanted pancreas in pigs.

Segmental allografts of the body and tail of the pancreas have been carried out in pigs using an open duct technique. Diabetes was induced by total pancreatectomy. Control animals on no immunosuppression survived an average of 17 days while animals receiving CyA survived 30 days. In the CyA group those with adequate serum levels of CyA survived 46 days while those with low levels survived 18 days. Once the animal became diabetic rejection was not reversible. In this model complement dependent cytotoxicity was more useful than lymphocyte mediated cytotoxicity in predicting rejection. However the rejected pancreas showed intensive mononuclear infiltration. Malabsorption resulting from total pancreatectomy used to induce diabetes may have contributed to the erratic CyA absorption. Prolonged and relatively normal pancreatic allograft function is possible, but adequate CyA levels must be achieved and maintained. Monitoring of serum levels is essential.

Establishing a district palliative care team for children.

The children's palliative care team aims to ensure a high standard of care and support for children with life-threatening illnesses and their families. The team works through primary care teams and with hospital staff to ensure consistency and continuity of care and to maintain awareness of good practice and acts as a resource for staff from independent and voluntary agencies. The team consists of a consultant community paediatrician, clinical child psychologist, a dedicated social worker, sick children's trained district nurse, a senior member of staff from the children's ward, a health visitor, a school nurse, and a special school nurse. Other professionals are co-opted to the team as and when considered necessary, for example hospice consultant, pain specialist, dietician, paediatric pharmacist, chaplain. This paper describes how the children's palliative care team was set up and the first 2 years of its functioning.