INVESTIGATIONS ON NITROGEN COMPOUNDS AND NITROGEN METABOLISM IN PLANTS. I. THE REACTION OF NITROGEN COMPOUNDS WITH NINHYDRIN ON PAPER: A QUANTITATIVE PROCEDURE.
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Biomedical subjects
Publications and source records attributed to J F Thompson.
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Isolated limb perfusion (ILP) with cytotoxic agents is an effective but complex procedure. Isolated limb infusion (ILI) has been developed as a simpler alternative. Catheters are inserted percutaneously into the axial artery and vein of the affected limb and a pneumatic tourniquet is inflated proximally. Cytotoxic agents are then infused through the arterial catheter and circulated with a syringe for 15 to 20 minutes. Progressive hypoxia occurs, but normothermia is maintained. To date, 175 ILIs have been performed: 164 for melanoma and 11 for other tumours. Results obtained are similar to those obtained by conventional ILP. Morbidity is low and treatment of frail and elderly patients who would not tolerate ILP is possible. An elective double ILI protocol can be used to obtain the additional benefits of fractionated chemotherapy. The possibility of increasing ILI response rates by using other drugs and drug combinations and by multiple fractionated dosing is being investigated.
The clinical and histological features of 13 malignant melanomas in children less than 13 years of age in New South Wales, Australia, were compared with those in a control group of children with 15 Spitz nevi, 4 of which were considered atypical, and 2 unusual compound nevocellular nevi. Six of the controls had been previously diagnosed histologically as malignant melanoma. The objective observations made by one or more histopathologists experienced in reporting melanocytic lesions, and the clinical details, mainly from the Sydney Melanoma Unit files, were entered on a detailed protocol. Evaluation was assisted by the use of SPSS-X software on a mainframe VAX computer. Six of the 13 children with malignant melanoma died with their disease. The most frequent clinical features found in the malignant melanomas were bleeding, ulceration, itching, and black or variegated color. Recent enlargement and darkening were noted in the majority of both the malignant melanomas and the Spitz nevi. Histological features favoring malignancy in this series were mitoses within 0.25 mm of the dermal margin of the melanoma, a dermal mitotic rate exceeding 2/mm2, ulceration, surface exudate, large pigment granules, and clear-cell differentiation. The median thickness of the malignant melanomas was 1.3 mm but in the 4 children who died with melanoma the median thickness was 2.9 mm. Absence of mitoses, predominance of spindle cells, and diffuse maturation favored Spitz nevus. The median thickness of the Spitz nevi was 0.7 mm.
In patients with advanced or recurrent melanoma confined to a limb, hyperthermic isolated limb perfusion (ILP) with melphalan produces complete remission in 35-40% of cases and partial remission in a further 35-40%. Mild or moderate limb toxicity is usual, but severe toxic reactions in the limb sometimes occur. After preliminary reports suggested that cisplatin administered by ILP was even more effective than melphalan yet less toxic, a study was undertaken to further assess the value of hyperthermic ILP with cisplatin in the management of limb melanoma. Ten patients were treated. The procedure failed to eliminate melanoma in the limb in 5 of the 6 who received therapeutic ILPs for recurrent disease, and recurrence developed in 2 of the 4 patients who received prophylactic ILPs. Toxicity in the perfused limbs was unacceptably high, with 2 of the 10 patients having severe reactions, one necessitating amputation. We conclude from the results of this study and from a review of literature that neither cisplatin nor any other drug or drug combination so far used for ILP in melanoma patients achieves results which are clearly superior to those achieved with melphalan. Studies are currently in progress investigating double perfusion protocols, new strategies with regional hyperthermia, and the administration by ILP of biological response modifiers such as tumor necrosis factor and interferon. However, for the present, hyperthermic ILP with melphalan remains the treatment most likely to be successful in eliminating or controlling advanced or recurrent melanoma in a limb.
BACKGROUND: The incidence of epitrochlear lymph node metastasis for patients with melanomas on the hand or forearm is disputed, and management guidelines for these nodes are unclear. METHODS: The records of 13,139 consecutive melanoma patients were reviewed to document the incidence of metastatic disease in epitrochlear nodes. The frequency of direct lymphatic drainage to epitrochlear nodes was determined for 109 patients with melanomas of the distal upper limb who had undergone preoperative lymphoscintigraphy. RESULTS: Nine of 801 patients (1.1%) with upper limb primary melanomas developed metastatic disease in an epitrochlear node, and one other patient with an occult primary tumor did so. Six of these ten patients underwent elective axillary node dissection at the time of surgery for epitrochlear node disease, and three were found to have metastatic disease in an axillary node. Epitrochlear node metastasis occurred in only two of 83 (2.4%) patients with upper extremity melanoma who underwent therapeutic axillary dissection. Of the 109 patients who underwent lymphoscintigraphy, four (3.7%) demonstrated lymphatic drainage to an epitrochlear node. CONCLUSIONS: Epitrochlear nodal involvement from melanoma of the distal upper extremity is rare, and routine epitrochlear node clearance at the time of either elective or therapeutic axillary dissection for upper extremity melanoma is not indicated. However, it is desirable to perform an axillary dissection whenever surgery for metastatic disease in an epitrochlear node is performed.
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A 10-year-old boy developed internal herniation of the small intestine associated with significant ischemia, which was reduced without resection. Severe diarrhea, hypoalbuminemia, and lymphopenia ensued while he was receiving total parenteral nutrition. Resolution of symptoms occurred only after resection of an area of ileum, which revealed persistent inflammation and atrophy. Postischemic epithelial cell regeneration of the intestine is discussed in light of this patient's protein-losing enteropathy.
In contrast to observations in other species, neither enteric mucosal weight, protein content, nor DNA content of either the suckled or artificially fed guinea pig changes over the first 24 h following term birth. In guinea pigs delivered 5 days prematurely, however, statistically significant increases in proximal enteric mucosal mass (38%), protein content (51%), and DNA content (35%) occur in suckled animals over the first 24 h of life but not in artificially fed animals. These observations illustrate that the enteric mucosal hyperplasia secondary to natural feeding, quantitatively and temporally, is species-specific and suggest that this effect is manifested only during a finite period of intestinal development. They raise doubts, therefore, concerning the importance of early enteric mucosal hyperplasia in adaptation of all species to extrauterine life.
Vascular smooth muscle cells must monitor and respond to their mechanical environment; however, the molecular response of these cells to mechanical stimuli remains incompletely defined. By applying a highly uniform biaxial cyclic strain to cultured cells, we used DNA microarray technology to describe the transcriptional profile of mechanically induced genes in human aortic smooth muscle cells. We first identified vascular endothelial growth factor (VEGF) as a mechanically induced gene in these cells; VEGF served as a positive control for these experiments. We then used a DNA microarray with 5000 genes with putative functions to identify additional mechanically induced genes. Surprisingly, relatively few genes are mechanically induced in human aortic smooth muscle cells. Only 3 transcripts of 5000 were induced >2.5-fold: cyclooxygenase-1, tenascin-C, and plasminogen activator inhibitor-1. Downregulated transcripts included matrix metalloproteinase-1 and thrombomodulin. The transcriptional profile of mechanically induced genes in human aortic smooth muscle cells suggests a response of defense against excessive deformation. These data also demonstrate that in addition to identifying large clusters of genes that respond to a given stimulus, DNA microarray technology may be used to identify a small subset of genes that comprise a highly specific molecular response.
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Azathioprine and prednisolone may lead to intolerable long-term side effects in some patients with a renal allograft. We have converted 9 patients with stable grafts but severe side effects from conventional immunosuppression to cyclosporine alone. While the steroid side effects largely resolved and there were no problems with acute rejection associated with conversion, the long-term follow up of these patients has demonstrated a number of problems. The average follow-up period since conversion is now 2 years: 2 patients have died, 2 grafts have been lost, and 1 patient required conversion to azathioprine. Chronic nephrotoxicity, gout, indomethacin-induced acute oliguria, and squamous cell carcinomas were the most troublesome effects seen. The disadvantages of conversion outweigh the advantages in most of the patients that we converted.
The historical development of integrated treatment programs for locally advanced or aggressive cancers, for which the results of surgical excision or radiotherapy are unsatisfactory, is reviewed. Chemotherapy should be used first (induction chemotherapy), while tumour vasculature is intact; intra-arterial infusion gives a greater regional effect. Central residual tumour may be eradicated by subsequent radiotherapy and/or surgery. Regional induction chemotherapy is particularly useful in treating locally advanced stage III breast cancer, locally advanced head and neck cancer, gastric cancer, and locally advanced sarcomas and melanomas of the limbs. A team approach, involving surgical and medical oncologists, radiotherapists, immunologists, and others should improve the results in these patients.
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