FK506 in combination with methotrexate for the prevention of graft- versus-host disease after marrow transplantation from matched unrelated donors

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus- host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno- occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan- Meier estimates of disease-free survival at 2 years for good-risk, poor- risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.     

Spacing of cytochrome oxidase blobs in visual cortex of normal and strabismic monkeys

Some models of visual cortical development are based on the assumption that the tangential organization of V1 is not determined prior to visual experience. In these models, correlated binocular activity is a key element in the formation of visual cortical columns, and when the degree of interocular correlation is reduced the models predict an increase in column spacing. To examine this prediction we measured the spacing of columns, as defined by cytochrome oxidase (CO) blobs, in the visual cortex of monkeys whose binocular vision was either normal or disrupted by a strabismus. The spatial distribution of blobs was examined in seven normal and five strabismic macaques. Tangential sections through the upper layers of the visual cortex were stained to reveal the two-dimensional (2D) pattern of CO blobs. Each blob was localized and their center-to-center spacing, packing arrangement and density were calculated using 2D nearest-neighbor spatial analyses. The mean center-to-center spacing of blobs (590 microm for normally reared and 598 microm for strabismic macaques) and the mean density of blobs (3.67 blobs/mm2 for normally reared and 3.45 blobs/mm2 for strabismic macaques) were not significantly different. In addition, the 2D packing arrangement of the blobs was not affected by strabismus. While it is clear that neural activity plays a key role in the elaboration and refinement of ocular dominance cortical modules, we conclude that it does not determine the spatial period of the pattern of CO blobs. This suggests that aspects of the neural circuitry underlying the columnar architecture of the visual cortex are established prenatally and its fundamental periodicity is not modifiable by experience.      

F4 (K88) fimbrial adhesin FaeG expressed in alfalfa reduces F4+ enterotoxigenic Escherichia coli excretion in weaned piglets

Transgenic plants are attractive bioreactors to large-scale production of recombinant proteins because of their relatively low cost. This study reports for the first time the use of transgenic plants to reduce enterotoxigenic Escherichia coli (ETEC) excretion in its natural host species. The DNA sequence encoding the major subunit and adhesin FaeG of F4+ ETEC was transformed into edible alfalfa plants. Targeting of FaeG production to chloroplasts led to FaeG levels of up to 1% of the total soluble protein fraction of the transgenic alfalfa. Recombinant plant-produced FaeG (pFaeG) remained stable for 2 years when the plant material was dried and stored at room temperature. Intragastric immunization of piglets with pFaeG induced a weak F4-specific humoral response. Co-administration of pFaeG and the mucosal adjuvant cholera toxin (CT) enhanced the immune response against FaeG, reflected a better induction of an F4-specific immune response. In addition, the intragastric co-administration of CT with pFaeG significantly reduced F4+ E. coli excretion following F4+ ETEC challenge as compared with pigs that had received nontransgenic plant material. In conclusion, transgenic plants producing the FaeG subunit protein could be used for production and delivery of oral vaccines against F4+ ETEC infections.     

Management of Vascular Injuries in a Forward Hospital

Background

Management of vascular injuries poses a challenging problem under warlike conditions. Several authorities recommend limb revascularisation only within first 6-8 hours, as the outcome after delayed revascularisation is poor.

Methods

A retrospective analysis of 61 consecutive patients with vascular injury in a forward hospital over a 25- month period was carried out.

Results

Vascular injuries constituted 3.1% of all injuries. The mean injury to treatment delay (lag time) was 11 hours, and 10 patients received treatment after 12 hours. The overall amputation rate was 15%, but only 6.5% for those revascularised within 12 hours and 44% for those undergoing surgery after 12 hours (Chi-square 4.59, p < 0.05). Presence of associated fractures was associated with an adverse outcome (Chi-square 4.24, p < 0.05), as was ligation in comparison to revascularisation (Chi-square 7.86, p < 0.005). Popliteal injuries were associated with a high amputation rate.

Conclusions

Failure to revascularise (ligation of artery), presence of associated fracture, and restoration of circulation beyond 12 hours are associated with a high amputation rate.Key Words: Vascular injuries, trauma, amputation     

Parathyroid Neoplasms: The Army Hospital (Research & Referral) Experience

Background

Neoplasms of the parathyroid are common but parathyroid carcinoma is exceptionally rare. In contrast to most other malignant endocrine tumours that are usually less hormonally active, malignant parathyroid tumours are hyper functional. Malignant parathyroid tumours pose a diagnostic dilemma for the pathologist.

Objective

To study the clinicopathological profile of a case series of parathyroid neoplasms and determine features which facilitate a malignant diagnosis.

Methods

A retrospective analysis of seven cases of surgically treated parathyroid tumours over a three-year period at a single centre was done. Clinical, haematological, biochemical, and radiological data was accrued from medical records. The histopathology slides were reviewed along with the clinicopathological profile in an attempt to delineate markers of malignancy.

Results

Patients ranged from 30 to 58 years of age. Males and females were approximately equal. Weakness and bone pain were the commonest presenting symptoms. Over 50% had significant hypercalcaemia and all had elevated serum parathormone. Clinically apparent mass was seen in only one. All tumours were successfully localised using CT scan and MRI. Thick fibrous capsule and broad septal fibrosis was seen in both the carcinomas; these were thin in the adenomas. Mitotic counts of 1-3 per high power field (HPF), capsular invasion and nodal metastasis were noted in the malignant tumours.

Conclusion

Elevated serum calcium and parathormone values point to a parathyroid neoplasm. Current imaging modalities are successful in localising the tumour preoperatively. Markedly elevated serum calcium, broad fibrous bands, mitotic counts and capsular invasion are indicators of malignancy.Key Words: Parathyroid, Adenoma, Carcinoma     

Atrophy of the residual alveolar ridge following tooth loss in an historical population

Oral Diseases (2010) 17 , 33–44 Objectives: To study the natural aetiopathology of jaw atrophy after tooth loss, unaltered by prosthetic procedures, an historical population without modern dental treatment was examined. Methods: Based on the hypothesis that there are predictable changes in shape during jaw‐atrophy, frequency and degree of atrophy as well as clinical aspects of bone quality and resorption were determined in the skeletal remains of 263 individuals. The potential association between age and frequency/severity of atrophy was analysed. Results: Atrophy in at least one jaw segment was present in 45.2% of the analysed jaw specimens. The residual ridge underwent a series of changes in shape and height following the pattern of resorption described for modern populations. The severity of these alterations was associated with the age of the individual and the region within the jaw. Atrophy was frequently related to structural degradation of the covering cortical layer. Conclusions: These findings prove that atrophy of the jaw evidently does occur, displaying similar patterns of resorption in a population without modern prosthetics, where the negative effect of ill‐fitting dentures is excluded. The basic information about alterations of shape and the cortical layer covering the residual crest might help to provide a deeper insight into aetiopathological mechanisms of this common oral disease.