Search PubMed⌕ Search

Biomedical subjects

P N Plowman

Publications and source records attributed to P N Plowman.

At least 19 recordsLinked to original sources
PubMed2006

Clinical and cellular ionizing radiation sensitivity in a patient with xeroderma pigmentosum.

XP14BR is a cell line derived from a xeroderma pigmentosum (XP) patient from complementation group C. The patient was unusual in presenting with an angiosarcoma of the scalp, treated by surgical excision and radiotherapy. Following 38 Gy in 19 fractions with 6 MEV electrons, a severe desquamation and necrosis of the underlying bone ensued, and death followed 4 years later. The cell line was correspondingly hypersensitive to the lethal effects of gamma irradiation. We had previously shown that this sensitivity could be discriminated from that seen in ataxia-telangiectasia (A-T). The cellular response to ultraviolet radiation below 280 nm (UVC) was characteristic of XP cells, indicating the second instance, in our experience, of dual cellular UVC and ionizing radiation hypersensitivity in XP. We then set out to evaluate any defects in repair of ionizing radiation damage and to verify any direct contribution of the XPC gene. The cells were defective in repair of a fraction of double strand breaks, with a pattern reminiscent of A-T. The cell line was immortalized with the vector pSV3neo and the XPC cDNA transfected in to correct the defect. The progeny derived from this transfection showed the presence of the XPC gene product, as measured by immunoblotting. A considerable restoration of normal UVC, but not ionizing radiation, sensitivity was observed amongst the clones. This differential correction of cellular sensitivity is strong evidence for the presence of a defective radiosensitivity gene, distinct from XPC, which is responsible for the clinical hypersensitivity to ionizing radiation. It is important to resolve how widespread ionizing radiation sensitivity is amongst XP patients.

Cell Death↗
PubMed2005

Comparison of radiosurgery planning modalities for acoustic neuroma with regard to conformity and mean target dose.

PURPOSE: To evaluate dose conformity and mean target dose in light of previous comparative studies and state-of-the-art radiosurgery delivery modalities. MATERIALS AND METHODS: Seven patients with acoustic neuromas deemed clinically suitable for linear accelerator or Gamma Knife radiosurgery were planned such that the minimum doses for any plan were equal. Gamma Knife plans were prepared in three ways: by altering the prescription of previously published data, by hand and with the assistance of an automatic planning algorithm (wizard). The linear accelerator plans were prepared utilizing a micro-multileaf collimator in both static and dynamic modes. The dose volume histogram analyses lead to a measure of conformity and the mean and minimum target dose for each plan. Statistical significance was calculated as each planning modality was compared with every other. RESULTS: All Gamma Knife plans demonstrated a statistically significantly better conformity when compared with fixed field linear accelerator techniques. When compared to linear accelerator techniques the wizard-assisted Gamma Knife plans demonstrated significantly better conformity. The mean target dose for all the Gamma Knife plans was significantly higher than that of the linear accelerator plans (19.2 Gy vs. 13.4 Gy). CONCLUSIONS: Conformity of the prescription isodose to the target shape is of major importance in radiosurgery. The modalities compared represent commercially available and widely accepted systems. Gamma Knife plans derived using the 'wizard' option and finalized by hand yield the best conformity.

Algorithms↗
PubMed2005

Thyroid orbitopathy possibly predisposes to late-onset of periocular lymphoma.

AIM: The prevalence of thyroid orbitopathy, compared with an estimate for the United Kingdom population, is examined in a large cohort of patients treated for periocular lymphoma. PATIENTS AND METHODS: Clinical details were reviewed for patients presenting to the Orbital Clinic at Moorfields Eye Hospital with biopsy-proven periocular lymphoma. Recorded evidence of prior thyroid gland abnormality or thyroid eye disease was sought and treatment details recorded, together with that of the subsequent periocular lymphoma. The calculated prevalence of thyroid orbitopathy in our patients with periocular lymphoma was compared with an estimate based upon published figures for a United Kingdom population. RESULTS: Of 369 patients with periocular lymphoma, 20 (5%) had a history of thyroid disease and adequate notes were available in 10 cases: All had autoimmune thyrotoxicosis between 11 and 27 years (median 17.5) before diagnosis of periocular lymphoma and 6/10 had thyroid orbitopathy-none receiving orbital radiotherapy for treatment of their thyroid eye disease. Using a calculated estimate for the UK prevalence of thyroid orbitopathy, the probability of even these six cases of ophthalmopathy among 369 patients with periocular lymphoma is very low (P=0.007). CONCLUSION: Compared with a population estimate, patients with periocular lymphoma had a significantly greater prevalence of preceding thyroid orbitopathy, with a median latency of 17 years. Thyroid orbitopathy possibly predisposes to later local lymphoma in a manner similar to the late emergence of lymphoma with other chronic inflammatory diseases-such as Sjögren's syndrome, Hashimoto's thyroiditis, coeliac disease, or Helicobactergastritis.

Adult↗
PubMed2005

Final adult height and body mass index after cure of paediatric Cushing's disease.

OBJECTIVE: Linear growth data after cure of paediatric Cushing's disease (CD) have been reported infrequently. We evaluated final adult height (FH) and body mass index (BMI) in a cohort of paediatric patients treated successfully for CD. PATIENTS AND METHODS: Fourteen patients (10 male, age range 6.4-16.6 years) fulfilled the diagnostic criteria for CD. All had had transsphenoidal surgery (TSS), combined with pituitary irradiation (RT) (45 Gy in 25 fractions) in six. All were cured (post-TSS cortisol < 50 nmol/l or mean cortisol post-RT < 150 nmol/l). Subjects analysed had bone ages at diagnosis of < 15 'years' (male) and < 13 'years' (female). RESULTS: At diagnosis, height SDS was [mean (range)]-2.5 (-4.2 to -0.8) and body mass index (BMI) SDS +2.7 (0.8-5.1). Following cure, 13 patients had GH deficiency (peak GH < 20 mU/l) and were treated with hGH (+ GnRH analogue in four). Height SDS at FH (n = 10) or latest assessment (n = 4) was -1.3 (-3.9-0.2) and increased compared to diagnosis (P < 0.01). The difference between final or latest height SDS and target height SDS was -1.2 (-3.3-0.5), that is less (P < 0.01) than the difference between the height SDS at diagnosis and target height SDS of -2.4 (-3.9 to -0.5). At final height or latest assessment, BMI SDS was +1.7 (0.4-6.2), being decreased compared to diagnosis (P < 0.05) but greater than the normal population (P < 0.01). CONCLUSION: Catch-up growth was demonstrated in paediatric patients cured from CD, with the majority achieving FH within target height range. Early diagnosis and treatment of GH deficiency is recommended to achieve optimal long-term growth. Excess adiposity remains a potential long-term complication.

Adolescent↗
PubMed2005

Tumour surveillance imaging in patients with extrapituitary tumours receiving growth hormone replacement.

OBJECTIVE: GH replacement is widely used in the management of patients with adult-onset (AO)-GH deficiency (GHD). In most cases, AO-GHD arises as a result of pituitary/peripituitary tumours and/or their treatment, but the effect of GH replacement on recurrence/regrowth of these tumours is unknown. The aim of this study was to examine the effect of GH replacement in a group of patients with primary tumours of the parasellar region, many of which (e.g. craniopharyngioma, glioma or germ cell tumours) might be anticipated to have a higher recurrence rate than secretory and nonsecretory anterior pituitary tumours. PATIENTS AND DESIGN: We report here our experience of prospective imaging in 50 consecutive patients (21 males; mean age 45.9 years) with nonanterior pituitary parasellar tumours treated with GH. All had severe GHD (peak serum GH 9 mU/l or less on dynamic testing) and were treated with an identical dose-titration regimen to maintain serum IGF-I concentrations between the median and upper end of the age-adjusted normal range. The primary diagnoses were: craniopharyngioma (28), germ cell tumour (8), arachnoid cyst (4), meningioma (4), glioma (4) and mensenchymal tumour (2). External pituitary irradiation had been given to 37 (74%) of patients. Measurements Surveillance imaging (magnetic resonance imaging (MRI) 70%, computed tomography (CT) 16%, both 14%) was performed at baseline (prior to GH), at 6--12 months, and then again yearly or as clinically indicated. Median follow-up was 36 months (range 7--129 months). All images were reviewed by the same radiologist. RESULTS: Four patients had an apparent increase in tumour volume but in only one patient was it considered necessary to abandon GH replacement. In two of the four cases marginal increases in cystic parasellar tumours were not progressive; and in the fourth case apparent recurrence of a suprasellar germ cell tumour was shown to be acellular fibrous tissue only on biopsy. In all other cases either the appearances were unchanged or the amount of tissue was reduced during long-term follow-up on GH. CONCLUSIONS: Overall, GH appears safe with respect to tumour recurrence over this time period in this patient group. Comparison with similar prospective series in patients not receiving GH replacement is desirable.

Adult↗
PubMed2004

Pineal parenchymal tumours: I. Pineocytoma: a tumour responsive to platinum-based chemotherapy.

Pineocytoma and pineoblastoma are now recognised as a spectrum of the same disease. Three cases of pineocytoma (grade I-II) are presented, in which platinum-based chemotherapy was used with some success, either as part of primary therapy or at the time of relapse. With the recent reclassification of pineal parenchymal tumours into a grade I-IV continuum, the place of chemotherapy, previously only well-established in pineoblastoma, is discussed.

Adult↗
PubMed2004

Pineal parenchymal tumours: II. On the aggressive behaviour of pineoblastoma in patients with an inherited mutation of the RB1 gene.

This report relates to a retrospective analysis of two non-randomised cohorts of patients with pineoblastoma, with some differences in presenting features and treatment characteristics. We have identified a large difference in survival depending on the possession or otherwise of the mutated RB (retinoblastoma) gene in the genome/karyotype. Eight children with familial retinoblastoma (non-metastatic at presentation) developed pineoblastoma and were treated by chemotherapy and radiotherapy. The survival of these patients was compared with the survival of nine non-metastatic sporadic cases of pineoblastoma similarly staged and treated. One out of eight children having the RB mutation in the genome survived compared with seven out of nine in the group with sporadic pineoblastoma (P = 0.002). It is suggested that the inheritance of the mutated retinoblastoma gene is not only causal in the generation of this tumour type but, in a way that is yet to be defined, renders such tumours more aggressive or less responsive to therapy. With the current interest in the role of RB mutations in other cancers (where the prognostic import of single genes is less easily identified), this observation may have wider relevance.

Brain Neoplasms↗
PubMed2004

Successful treatment of childhood-onset Cushing's disease is associated with persistent reduction in growth hormone secretion.

OBJECTIVE: Although Cushing's disease (CD) rarely occurs in childhood, affected children commonly fail to achieve predicted adult height. Hypercortisolaemia results in reduced GH secretion and GH-deficiency may persist or demonstrate delayed recovery after successful treatment of CD in adults. Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established. DESIGN AND PATIENTS: We performed a retrospective analysis of the GH status of 13 children (10 males; 12.8 +/- 1.0 years, mean +/- SE) who had undergone successful treatment of CD that occurred prior to the completion of linear growth. Each underwent transsphenoidal hypophysectomy, resulting in satisfactory control of glucocorticoid levels in 7/13 (54%). The remaining six patients (46%) received fractionated external beam irradiation (4500 Gy). At the time of GH assessment, circadian dynamics of cortisol were normal in eight patients and five were receiving titrated glucocorticoid replacement. MEASUREMENTS: GH status was assessed using the peak response to a provocative stimulus. Eleven out of 13 underwent testing with insulin-induced hypoglycaemia (nadir plasma glucose </= 2.2 mmol/l) and glucagon provocation was used in 2/13. Severe GH-deficiency was defined as a peak GH response < 9 mU/l, and a normal response as > 30 mU/l. Intermediate values were taken to represent subnormal GH status. Assessment of GH status was performed 39 +/- 10 months (median +/- SE) following successful treatment (range 9-108 months). RESULTS: Using these criteria 4/13 (31%) patients had severe GH-deficiency. Only 2/13 (15%) had a normal response. 7/13 (54%) achieved peak GH levels in the subnormal range. Those with multiple pituitary hormone deficiencies were most likely to have lower peak GH levels, but there was no clear effect of pituitary irradiation or relationship between duration post cure and peak GH response. CONCLUSION: GH-deficiency is common and may persist for many years following successful treatment of CD prior to completion of linear growth. External radiotherapy does not necessarily result in severe GH-deficiency in the short term. Assessment of GH status and consideration of GH treatment should be considered following treatment of CD in childhood and adolescence in order to maximize the opportunities to achieve a satisfactory final adult height. In those with subnormal GH responses, continued assessment is necessary to determine whether the GH axis subsequently recovers or if these patients develop features of the adult GH-deficiency syndrome.

Adolescent↗
PubMed2004

Dramatic response of malignant craniopharyngioma to cis-platin-based chemotherapy. Should craniopharyngioma be considered as a suprasellar 'germ cell' tumour?

The case is described of a 21-year-old woman, who developed a malignant tumour arising from a craniopharyngioma 14 years after the original diagnosis. The remarkable response of this malignant tumour ex-craniopharyngioma to cis-platin based chemotherapy, together with other midline tumour characteristics of craniopharyngioma, raise the question as to whether craniopharyngioma should any longer be separately considered from suprasellar germ cell tumour. This subject is discussed.

Adolescent↗
PubMed2004

A comparison of conventional, conformal and intensity-modulated coplanar radiotherapy plans for posterior fossa treatment.

Radiotherapy of the posterior fossa for medulloblastoma treatment can induce ototoxicity, especially when combined with cisplatin chemotherapy. Sensorineural hearing loss can be severe enough to cause permanent disability, which may compromise cognitive development in paediatric patients. This study evaluates the sparing of the cochlea in conventional radiotherapy, three-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT). CT scans of three patients were used to plan posterior fossa radiotherapy using coplanar beam arrangements. The posterior fossa and the cochlea were contoured as well as other organs-at-risk (non-posterior fossa brain, lenses, optic nerves, pituitary and cervical spinal cord). Three treatment plans were compared: conventional two-dimensional treatment (parallel-opposed lateral pair); 3D-CRT (two wedged posterior oblique fields); and a four-field coplanar IMRT plan. 3D-CRT and IMRT reduced cochlear doses to less than 70% of the mean target dose. These plans also reduced dose to the non-posterior fossa brain and cervical spinal cord. IMRT showed no advantage over 3D-CRT in sparing the optic nerves and lenses, compared with 3D-CRT. Normal tissue doses were higher in both conformal techniques than in the IMRT plans. Conformal techniques reduced the dose to the cochlea, non-posterior fossa brain and cervical spinal cord. The small size and proximity to the planning target volume (PTV) of the cochlea limited the effectiveness of the IMRT plan. Coplanar 3D-CRT was judged superior to coplanar IMRT, particularly in children, because it achieved adequate sparing of the cochlea and anterior cranial structures, such as the lenses and optic nerves, without compromising the dose to the posterior fossa.

Cerebellar Neoplasms↗
PubMed2004

The role of nuclear medicine in the diagnosis of cancer of unknown origin.

Cancer of unknown origin (CUO) is defined by the absence of any primary tumour in biopsy-proved metastatic cancer. CUO accounts for a 5-10% of all malignancies. These tumors have a specific biology with clinical characteristics of rapid progression and atypical metastases. Diagnostic evaluation is directed at the identification of treatable subset. Accurate diagnostic workup is crucial because both prognosis and survival rates depend mainly on detection of the primary tumor site. Although these patients undergo extensive imaging procedures, nuclear medicine techniques are under-utilized despite their ability of providing molecular information. Positron emission tomography has an emerging role in this clinical challenge along with other nuclear medicine methods including, bone scan, thyroid scintigraphy.

Biomarkers, Tumor↗