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Biomedical subjects

P H Morris-Jones

Publications and source records attributed to P H Morris-Jones.

At least 19 recordsLinked to original sources
PubMed1994

Pubertal growth in response to testosterone replacement therapy for radiation-induced Leydig cell failure.

The adolescent growth pattern of eight boys, who had puberty induced with androgen replacement therapy following radiation-induced Leydig cell failure, was studied from induction of puberty at a mean age of 13.1 years (range 11.6-14.5) to final height at mean age of 18.8 years (range 17.7-20.3). The mean gains during puberty (SD) for standing height, sitting height, and sub-ischial leg length were 18.56 cm (3.98), 10.46 cm (2.39), and 8.1 cm (2.01) respectively, which were significantly reduced compared with normal Tanner standards (P < .001). The peak velocity for each parameter occurred in the 1st year of induced puberty in contrast to the pattern in normal adolescence, although the mean peak velocity for each auxological parameter was not significantly different from the normal Tanner standards. The mean adult standing height (SD), 167.5 cm (9.88), and mean adult leg length (SD), 80.8 cm (6.19), were not significantly different from the normal Tanner standards, whereas the mean adult sitting height (SD), 86.7 cm (4.78), was shorter (P < .001). Three of the eight patients had a leg length standard deviation score less sitting height standard deviation score in excess of +2.96 suggesting the presence of significant skeletal disproportion. Seven of the eight boys reached target genetic height, though in six, the final height was below mid-parental height (P < .05). The modest loss in height potential was mainly due to radiation-induced skeletal dysplasia attenuating the growth of the spine. The families of boys with radiation-induced Leydig cell failure requiring androgen replacement therapy can be reasonably optimistic about height prognosis as seven of the eight boys reached target genetic height.

Adolescent↗
PubMed1993

Ovarian function following the treatment of childhood acute lymphoblastic leukaemia.

Ovarian function was assessed in 40 long term survivors who had received standard United Kingdom Acute Lymphoblastic leukaemia (UKALL) protocols and were in first clinical and haematological remission. A menstrual and pregnancy history was taken (median age at assessment: 18.8 (12-34.7) years) and the acquisition of adult secondary sexual characteristics confirmed in each patient. Basal bloods were taken for follicle stimulating hormone (FSH), luteinizing hormone (LH), and serum oestradiol estimations. Serum progesterone concentration was measured in those patients who were in the luteal phase of their menstrual cycle at assessment. In addition, menstrual cycle profiles of salivary progesterone concentrations were derived from daily samples in 12 patients. All patients achieved adult sexual development; median age at menarche was early at 12.4 (9.0-14.6) years and 37 of them have regular menses. Ten patients have had 14 live births, and evidence of ovulation was seen in a further 11 patients assessed in the luteal phase of the menstrual cycle. Four patients had damaged ovaries, two of whom show evidence of ovulation; three of the four received craniospinal irradiation and one received cyclophosphamide as part of her chemotherapy regimen. None of these patients has yet developed total ovarian failure or required sex steroid replacement therapy. The medium term outlook for ovarian function is good for the majority of childhood ALL survivors. The spinal component of craniospinal irradiation is a major risk factor for ovarian damage, and cyclophosphamide may be a contributory factor. A premature menopause remains a possibility if significant follicular depletion has occurred at the time of cytotoxic treatment.

Adolescent↗
PubMed1993

Childhood B cell lymphomas arising in the mediastinum.

AIMS: To report the clinical features and pathology of four childhood cases of primary mediastinal non-Hodgkin's lymphoma of non-lymphoblastic pathology. METHODS: Biopsy material was fixed in formol-saline and routinely processed and stained. Immunohistochemical staining was performed on paraffin wax embedded sections using the alkaline phosphatase anti-alkaline phosphatase method. RESULTS: The four patients presented with a large mediastinal mass and symptoms consistent with superior vena cava syndrome secondary to lymphoma. None of the patients had any clinically important disease outside the mediastinum. The four tumours had a histological appearance similar to diffuse large cell non-Hodgkin's lymphoma with sclerosis. Immunohistochemical staining showed that these tumours were of B cell origin. One patient died from infection during treatment and two patients died with progressive disease. The remaining patient remained well 43 months off all treatment. CONCLUSIONS: These four cases further illustrate the heterogeneity of paediatric large cell lymphomas. Clinically, they seem to be equivalent to the B cell lymphoma of the mediastinum, sclerosing type, that is seen in young (predominantly female) adults. The clinical and biological features of this type of tumour in childhood are largely unknown. Using standard treatment protocols, this tumour seems to have a poor prognosis and its optimal treatment therefore requires further clarification.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

A novel variant of growth hormone (GH) insufficiency following low dose cranial irradiation.

OBJECTIVE: We aimed to investigate the effect of low dose (1800 cGy) prophylactic cranial irradiation on physiological growth hormone secretion. DESIGN: We performed an analysis of 24-hour serum GH profiles using 20-minute sampling. PATIENTS: Forty-four children were studied, of whom 21 were long-term survivors of acute lymphoblastic leukaemia and 23 were normal children. They were further subdivided into prepubertal, pubertal and post-pubertal groups. MEASUREMENTS: GH profiles were analysed by autocorrelation, Fourier transformation and spectral analysis of stationarized data, and peak detection using the Pulsar peak detection program. RESULTS In the normal children, there was a significant increase in the median (range) area under the curve (AUC) of the GH profile between the prepubertal and pubertal groups (62 (11-124) and 137 (142-158) IU/I/h respectively, (P less than 0.01)). There was also a change in the spectral analysis through puberty. The dominant frequencies were spread widely in the prepubertal and post-pubertal groups but sharply focused in the pubertal group. In the cranially irradiated children there was no significant increase in AUC between the prepubertal (62(13-110) IU/I/h) and pubertal groups (92 (14-163) IU/I/h). The wide range of dominant frequencies persisted in the pubertal cranially irradiated group due to the presence of additional high frequency pulses. The impression of a disturbance of the periodicity of GH secretion in the cranially irradiated pubertal group was further supported by the finding that the autocorrelation function in this group alone was not significantly different from that which would arise from random data. CONCLUSIONS: A novel form of GH insufficiency has been observed after low dose irradiation in childhood in which an abnormality of periodicity and a quantitative reduction in GH secretion appears restricted to puberty.

Adolescent↗
PubMed1991

Response rates in relapsed Wilms' tumor. A need for new effective agents.

Three hundred eighty-one children with Wilms' tumor were treated in the United Kingdom Children's Cancer Study Group WT1 Study (1982 to 1986). Seventy-one patients had relapses during or after treatment with surgery and chemotherapy, and radiation therapy, depending on stage and histologic characteristics. Forty-nine patients were evaluable for disease response to second-line chemotherapy alone. Evaluation of response to chemotherapy was impossible in the remaining patients because either surgery or radiation therapy was used at the time of relapse. With second-line combination chemotherapy (which included ifosfamide, etoposide/VM26, cisplatin/carboplatin, bleomycin, melphalan, and Thiotepa [Lederle Laboratories, Pearl River, NY]), there were five complete responses and 12 partial responses. In patients with favorable histologic findings, six of nine with Stage I, five of ten with Stage II, none of 11 with Stage III, three of 16 with Stage IV, and one of five with Stage V disease survived. Two survivors were treated with chemotherapy alone; the others received combined treatment with chemotherapy, radiation therapy, and/or surgery. For those with unfavorable histologic findings of any stage, only two of 20 survived. The authors conclude that, even for patients with localized disease with favorable histologic findings, the "salvage" rate is little more than 50%, and for all other stages and histologic findings the likelihood of cure after relapse is remote. There is clearly a need for additional effective chemotherapeutic agents for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Male fertility in long-term survivors of childhood acute lymphoblastic leukaemia.

To study long-term testicular function following the treatment of acute lymphoblastic leukaemia (ALL) in childhood, 37 young adult males were assessed at two separate time points. The initial assessment was made by a wedge testicular biopsy after completion of treatment (median 9.7 years; range 4.1-16.3 years) and the subsequent assessment (median 18.6 years; range 15.4-26.8 years) consisted of the clinical examination of pubertal stage, measurement of serum gonadotrophins and testosterone and, in 19 patients, semen analysis. All 37 men completed pubertal development normally and had a testosterone concentration within the normal adult range. Six men showed evidence of severe damage to the seminiferous epithelium, five were azoospermic and one, who did not provide semen for analysis, had a reduced mean testicular volume (11 mls; normal greater than or equal to 15 mls) and a raised basal FSH level (13 UI 1-1; normal less than or equal to 6 IU 1-1). All six men with germ-cell damage had received either cyclophosphamide or both cyclophosphamide and cytosine arabinoside as part of their chemotherapy regimen. Approximately 10.7 years earlier all 37 men had undergone a testicular biopsy after completion of their chemotherapy. Morphological damage to the seminiferous epithelium had been calculated by estimating the tubular fertility index (TFI), which is the percentage of seminiferous tubules containing identifiable spermatogonia (age-matched normal = 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Effect of abdominal irradiation on growth in boys treated for a Wilms' tumor.

To study the effect of abdominal irradiation on spinal growth in childhood we have measured final height, sitting height, and leg length in 30 male survivors of a Wilms' tumor. Twenty-one patients received whole abdominal irradiation by either megavoltage therapy (MV: n = 11) or orthovoltage therapy (OV: n = 10); the remainder received flank irradiation. To examine the effect of the adolescent growth spurt on the irradiated spine we have followed prospectively seven patients who received whole abdominal irradiation and nine patients who received flank irradiation through puberty. Compared to a normal population there is a modest reduction in median final standing height SDS (H.SDS: -1.15) accompanied by a marked reduction in median final sitting height SDS (S.HT SDS: -2.41) with no apparent effect on median subischial leg length SDS (SILL.SDS: 0.04). This reduction in spinal growth is reflected by a strongly positive disproportion score (DPS; [SILL SDS-S.HT SDS] + 2.81). The incidence of scoliosis after abdominal irradiation has been low (10%). During puberty there is a significant fall in median sitting height SDS after both whole abdominal (median fall: -0.9, P = 0.02) and flank irradiation (median fall: -1.85, P = 0.01), and this is reflected in a significant increase in disproportion (DPS: whole abdominal; median rise +1.4, P = 0.02: flank, median rise +1.34, P = 0.01). After MV irradiation there is a significant correlation between the degree of disproportion and the age at treatment (P less than 0.0005). The younger the patient is at treatment the more severe is the restriction on spinal growth and the shorter and more disproportionate they become as an adult. The estimated eventual loss in potential height from abdominal irradiation at the age of one is 10 cm and at five years is 7 cm.

Abdomen↗
PubMed1990

How curable is relapsed Wilms' tumour? The United Kingdom Children's Cancer Study Group.

Three hundred and eighty one children with Wilms' tumour were treated on the United Kingdom Children's Cancer Study Group WT1 Study (1980/6). Seventy one patients relapsed during or after treatment, which included surgery and chemotherapy, with irradiation depending on stage and histology. Despite treatment with various combinations of chemotherapy, surgery, and radiotherapy there were only 17 survivors. For unfavourable histology, any stage, only two of 20 survive. We conclude that, after relapse, even for patients who have had localised disease and favourable histology, the 'salvage' rate is little more than 50% and for all others the likelihood of cure is very small. Three of 41 children who relapsed less than 12 months from diagnosis survive, compared with 14 of 30 who relapsed later. It is essential that even with this 'good prognosis' tumour initial treatment is optimal and given by centres experienced in management of children's cancer. Furthermore, there is a clear need for additional effective chemotherapeutic agents for relapsed patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Gonadal dysfunction due to cis-platinum.

Gonadal function was studied in 15 patients 12 pubertal or postpubertal, and three prepubertal, who had been treated during childhood for nonmetastatic osteosarcoma of the long bones by chemotherapy regimens that included cis-platinum and adriamycin. Of seven postpubertal female patients assessed (mean age at diagnosis 16.5 years), three were amenorrhoeic and showed evidence of ovarian damage with raised gonadotrophin levels and a low serum oestradiol concentration. One patient who had regular periods had a raised luteal-phase follicle-stimulating hormone (FSH) concentration suggestive of gonadal dysfunction. Severe oligospermia or reduced testicular volumes in the presence of raised gonadotrophin levels were observed in three of the five pubertal males (mean age at diagnosis 13.25 years). A reliable assessment of gonadal function was not possible in three male patients who remained prepubertal at the time of study. The median total dose of cis-platinum received by those patients with gonadal damage (median dose, 490 mg) was significantly higher than in those patients with normal gonadal function (median dose, 300 mg) (P = 0.01). In the boys the damage to the testes was primarily directed at the germinal epithelium. Leydig cell function was intact and the males progressed spontaneously through puberty. In the girls, unlike the boys, there was evidence of reversibility of gonadal damage with time. This is the first study to show gonadal dysfunction due to cis-platinum and adriamycin therapy in childhood.

Adolescent↗
PubMed1989

Ovarian failure following abdominal irradiation in childhood: natural history and prognosis.

Ovarian function has been reviewed sequentially since 1975 in 53 patients treated in childhood between 1942 and 1985 for an intraabdominal tumour with surgery and external abdominal radiotherapy (XRT). Of 38 patients who received whole abdominal XRT (20-30 Gy), 27 failed to undergo or complete pubertal development (pubertal failure) and a premature menopause (median age 23.5 years) occurred in a further ten. Of 15 patients who received flank XRT (20-30 Gy), ovarian function (median age at last assessment 15.2 years) was normal in all but one in whom pubertal failure occurred. In only one patient, who developed pubertal failure after whole abdominal XRT and required sex steroid replacement therapy (HRT) to achieve normal secondary sexual characteristics, has there been evidence of reversibility of ovarian function with a documented conception at the age of 22.7 years. Five patients who developed pubertal failure required bilateral augmentation mammoplasties despite sex steroid replacement therapy. Four patients have had documented conceptions, all received whole abdominal XRT (20-26.5 Gy) and subsequently developed a premature menopause. There have been no live births, with all miscarriages occurring in the second trimester. The outlook for normal ovarian function following whole abdominal XRT is poor, flank XRT introduced intermittently from 1972, has resulted in less pubertal failure but the possibility of a premature menopause may with time become a reality.

Abdominal Neoplasms↗
PubMed1989

Ovarian failure following abdominal irradiation in childhood: the radiosensitivity of the human oocyte.

Ovarian function has been studied sequentially since 1975 in 19 patients treated in childhood for an intra-abdominal tumour with surgery and whole abdominal radiotherapy (total dose 30 Gy). Eleven patients received chemotherapeutic agents that are not known to cause gonadal dysfunction. All but one patient have developed ovarian failure with persistently elevated gonadotrophin levels (FSH and LH greater than 32 IU/litre) and low serum oestradiol values (less than 40 pmol/litre) before the age of 16 years. The majority (n = 12) did not progress beyond breast stage 1 without sex steroid replacement therapy. As the number of oocytes within the ovary declines exponentially by atresia from approximately 2,000,000 at birth to approximately 2000 at the menopause, we have been able to estimate that the LD50 for the human oocyte does not exceed 4 Gy.

Abdomen↗
PubMed1988

Growth in children treated for acute lymphoblastic leukaemia.

Growth was assessed in 82 children with acute lymphoblastic leukaemia (ALL) who achieved complete continuous first remission following treatment. 34 received prophylactic cranial irradiation at a total dose over 2000 cGy (group I) and 48 at a dose of 1800 cGy (group II). Chemotherapy was given over two or three years and was more intense in group II. Both groups showed a similar significant decrease in height standard deviation score (SDS) over four years (group I -0.31, group II -0.39). 15 children in group I were followed to ten years and continued to show restricted growth with a mean height SDS decrease of -0.84 (range 0 to -1.7). The greatest reduction in yearly decrements in height SDS occurred in the first year after diagnosis. In both groups height SDS increased significantly on completion of chemotherapy. Thus chemotherapy protocols contribute to growth retardation in ALL. In most of these children the mean loss of height over ten years was not sufficiently great to justify long-term growth hormone (GH) therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Prevention of cisplatin-induced hypomagnesemia.

Twenty-eight children were treated for various cancers with protocols that included dichlorodiamine platinum (cisplatin). Sixteen children were given intravenous magnesium after the administration of cisplatin, and 12 were given intravenous magnesium before and after administration of cisplatin. Serum magnesium concentration levels were monitored before, during, and after the full course of treatment and found to be lower in the first group of patients than in the second group. We recommend that magnesium supplements be given to patients receiving cisplatin during the precisplatin hydration period to prevent hypomagnesemia.

Adolescent↗
PubMed1988

Nutrition, infection, and morbidity in leukemia.

Seven of the 25 children with acute leukemia were malnourished on admission. Of the 11 children who presented with fever, 6 had protein energy malnutrition and a bacterial infection was confirmed. They had a lower total leucocyte count. Out of 18 well-nourished children, 5 presented with a fever and the causative organism was isolated in 1 patient. There were more patients with a palpable liver in the malnourished group, and they had a high morbidity due to infections during remission induction.

Acute Disease↗
PubMed1987

Evaluation of desmin as a diagnostic and prognostic marker of childhood rhabdomyosarcomas and embryonal sarcomas.

The diagnostic and prognostic relevance of desmin expression in 80 rhabdomyosarcomas (RMS) and 5 embryonal sarcomas (ES) was examined using a peroxidase anti-peroxidase staining procedure. Fifty-nine RMS but only one ES stained for desmin (P less than 0.05). The maximum percentage of desmin containing cells was 49 in RMS compared with only 1% in ES. Desmin positivity correlated inversely with survival (P less than 0.02) in that RMS with high proportions of desmin positive cells were associated with poorer prognoses than those containing fewer desmin positive cells. If the degree of expression of desmin is related to myogenic differentiation, then our results indicate that poorly differentiated RMS tend to have a better prognosis than the well differentiated tumours. One possible explanation is that the poorly differentiated RMS respond better to chemotherapy than to well differentiated RMS. A multivariant analysis incorporating desmin staining, treatment, histology, age and gender revealed that the two most significant independent prognostic factors were treatment and histology.

Desmin↗