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Biomedical subjects

A J Howat

Publications and source records attributed to A J Howat.

At least 55 records · Page 3Linked to original sources

Nucleolar organizer regions in Spitz nevi and malignant melanomas.

Nucleolar organizer regions (NOR) are loops of DNA that transcribe ribosomal RNA; they can be easily identified in formalin fixed paraffin embedded tissue using a silver (Ag) method. It has been suggested that the number of AgNOR per cell can differentiate between benign and malignant melanocytic lesions of skin. We have studied 29 Spitz nevi (SN) and 39 invasive malignant melanomas (MM) by the same silver method. SN showed between 1.0 and 1.6 AgNOR per cell with a mean of 1.2. MM counts ranged from 1.2 to 4.2 with a mean of 2.0. It is concluded that the AgNOR method cannot reliably differentiate SN from MM; however, a count of more than 2.0 AgNOR per cell would favor a diagnosis of MM rather than SN.

Flow Cytometry↗

Silver-stained nucleoli and nucleolar organizer region counts are of no prognostic value in thick cutaneous malignant melanoma.

Nucleolar organizer regions (NORs) can be stained by a simple one-step silver technique; the black dots formed are termed AgNORs. Often AgNORs are tightly clustered, appearing as one silver-stained nucleolus (AgNu). We have assessed this technique as a possible prognostic indicator for thick (greater than 3.0 mm) primary cutaneous malignant melanoma (CMM). Three groups were studied: (A) seven thick CMM that had not metastasized 8-20 years after excision; (B) three thick CMM that developed metastases 6-9 years after excision; and (C) twelve CMM that presented with metastases or developed them within 4 years of excision. Two methods of counting silver-stained black dots in nuclei were employed: one method counted easily discernible black dots consisting of AgNus and dispersed AgNORs; the other attempted to count actual AgNORs both dispersed and clustered within AgNus. Scores per nucleus by the first method were 1.5-6.7 in group A, 1.1-2.6 in group B, and 1.4-5.4 in group C. AgNOR counts by the second method were 6.2-13.0 in group A, 5.4-8.9 in group B, and 5.3-10.5 in group C. No significant difference was present between groups for scores by either method. Due to the subjectively, technical difficulty, non-reproducibility, and tedium associated with the second method of attempting to count individuals AgNORs, the first method is recommended. It is concluded that this technique is of no value in predicting prognosis for CMM.

Cell Nucleolus↗

Upper oesophageal gastric heterotopia: a prospective necropsy study in children.

Three hundred specimens of oesophagus obtained at necropsy from infants and children aged from 0 to 14 years, dying from a variety of causes, were examined prospectively for evidence of gastric heterotopia. Gastric heterotopia was observed in 63 (21%) of the whole series, representing a much higher incidence than reported previously. Excluding deaths in the perinatal period, the incidence appeared to be inversely related to age. Heterotopia was restricted to the subcricoid level of the oesophagus and often showed a close association with lymphoid tissue. There was no association with congenital malformation, and heterotopia occurred more commonly in those infants whose deaths were unexplained, although the reason for this association was unclear.

Adolescent↗

Malignant lymphoma of bone in children.

From 1960 to 1985 at the Royal Children's Hospital, Melbourne, seven cases of malignant lymphoma of bone (MLB) were identified in children younger than 16 years of age. Over the same period there were 88 cases of Ewing's sarcoma (ES), which illustrates the rarity of MLB. All cases were staged and treated according to protocols current at the time, namely, systemic chemotherapy with radiotherapy to the primary lesions. One child received radiotherapy alone as chemotherapy was not then available (1963). The disease-free five-year survival rate in our small series is 57%, which compares favorably with the 62% that we have calculated from survival data available from 26 previously reported cases of MLB in children and better than the 35% to 50% quoted in adult series of MLB. The main problem in differential diagnosis is distinguishing MLB from ES. A positive diagnosis of MLB rather than ES can be made, however, by observation of the characteristic reticulin staining pattern, the absence of cytoplasmic glycogen, and the ultrastructure.

Adolescent↗

Encephalomyelitis in two sisters who died suddenly at home.

Two sudden infant deaths of female siblings occurring at the ages of six and 5 1/2 months are reported. The temporal separation of their deaths was 14 months. Both showed virtually identical pathological findings within the central nervous system, consistent with encephalomyelitis. No causative agent, metabolic defect or common predisposing factor was identified and no evidence of a relationship to immunisation could be established.

Encephalomyelitis↗

Metastatic basal cell carcinoma.

A case of metastasizing basal cell carcinoma is presented. Although primary surgical excision appeared complete, local recurrence continued over the following 5 years terminating in metastases to lungs, kidneys, bones and lymph nodes.

Bone Neoplasms↗

Angiomatosis: a vascular malformation of infancy and childhood. Report of 17 cases.

Angiomatosis is a complex vascular malformation of infancy and childhood consisting of proliferating blood vessels with accompanying mature fat and fibrous tissue, lymphatics and sometimes nerves, that may involve skin, subcutaneous tissue, skeletal muscle and occasionally bone; lesions are non-encapsulated with poorly defined infiltrative borders. Treatment is surgical, with local recurrence being common. We report 17 cases of angiomatosis presenting in children. Recurrences occurred in 10 patients, with multiple recurrences occurring in four. One child was treated with foot amputation followed two years later by mid-thigh amputation in an attempt to control local disease. Histology in all cases showed a mixture of small and medium-sized blood vessels, fat, connective tissue and lymphatics; nerves were increased in several cases. All lesions showed nests of proliferating capillaries, arranged in a lobular pattern, pushing into adjacent muscle and fat. This appearance was not seen in a large comparison group of vascular soft tissue lesions, and may serve as an indicator of angiomatosis with its associated risk of recurrence.

Angiomatosis↗

Bilateral metachronous periosteal osteosarcoma.

The first case of bilateral metachronous periosteal osteosarcoma (OS) is reported. A 14-year-old white boy presented with a 1-month history of pain and swelling in his right thigh. Periosteal OS was diagnosed on a basis of the radiologic and pathologic findings. Treatment was with local resection and total hip replacement after a short course of high-dose methotrexate; multi-agent chemotherapy was continued postoperatively for 3 months. He remained well for 3 years. He then represented with a mass in the left femur that had been slowly growing for about 1 year. Radiologic and biopsy studies showed periosteal OS. Full investigations showed no evidence of metastatic disease. Treatment consisted of local resection without chemotherapy. He remained well for 6 months after the second excision until developing multiple pulmonary metastases. All further therapy was refused. The question as to whether the second tumor was a new primary lesion or a metastasis is discussed, together with possible differential diagnoses.

Adolescent↗

Renal glomerular size in infants with congenital heart disease and in cases of sudden infant death syndrome.

Recurrent apnoea and chronic hypoventilation have been implicated in the pathogenesis of the sudden infant death syndrome (SIDS) and markers of chronic hypoxaemia have been reported in such infants at post mortem examination. Markers of chronic hypoxaemia are common in cyanotic congenital heart disease. Glomerular enlargement in congenital heart disease is said to be related to hypoxaemia although the precise mechanism whereby this occurs is not clear. We have established a normal range of glomerular size for the postperinatal period and confirmed glomerular enlargement to be a common finding in children with congenital heart disease of similar age. In contrast glomerular size in SIDS is not different from controls. The results question the role of significant chronic hypoxaemia being involved in these deaths.

Autopsy↗

Primitive neuroectodermal tumour of the central nervous system associated with malignant rhabdoid tumour of the kidney: report of a case.

Malignant rhabdoid tumour of the kidney is a recently reported tumour presenting in young children. Irrespective of stage and despite intensive chemotherapy these tumours have a poor prognosis, with death usually occurring within a matter of months. A recent report has shown the association of second embryonal tumours of the central nervous system occurring in patients with the renal tumour; most of these second tumours have occurred in the posterior fossa. We report here an infant who presented with a mass in the right groin, showing features of a poorly differentiated sarcoma, possibly rhabdomyosarcoma. Further investigations revealed a tumour in the lower pole of the right kidney which was subsequently shown to be a malignant rhabdoid tumour. The child was given chemotherapy but re-presented at 10 months of age with hydrocephalus, irritability and spasms leading to death. At autopsy a large tumour was found filling the right lateral and third ventricles; histology showed a primitive neuroectodermal tumour with focal astrocytic differentiation. Residual rhabdoid tumour was restricted to a few para-aortic lymph nodes and focal lymphatic micrometastases in lungs. The association of two embryonal neoplasms of possible similar histogenesis is discussed.

Brain Neoplasms↗

Nuclear fragmentation and epithelioid change of germinal centers in the lymphoid tissue of child deaths.

Two hundred postmortems were studied retrospectively to assess the frequency of nuclear fragmentation (NF) and epithelioid change (EC) in the germinal centers of lymphoid tissues in children. Sections of spleen, mesenteric lymph node, tonsils, and appendix were included in the survey. Thirty-seven of 200 cases (18.5%) showed NF or EC or a combination. These morphological changes were considered to represent different stages of a common pathological reaction for which a classification is proposed. The type of lymphoid change correlated approximately with the duration of the preceding illness. Although more common between the ages of 1 and 3 years, they were found to extend throughout the age range studied. There was a negative correlation between the presence of NF and EC and the cause of death, but a significant association with clinical documentation of shock was present, supporting previous evidence that shock is the significant factor in pathogenesis.

Adolescent↗