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J Pritchard

Publications and source records attributed to J Pritchard.

At least 145 records · Page 8Linked to original sources
PubMed1991

Topical nitrogen mustard: an effective treatment for cutaneous Langerhans cell histiocytosis.

In 16 children with multisystem Langerhans cell histiocytosis (mean age 22 months, range 5 to 36 months) severe symptomatic skin involvement was treated with topical nitrogen mustard (mechlorethamine hydrochloride). In each case, rapid clinical improvement occurred within 10 days; subsequent complete healing was observed in 14 children, and partial healing in 2 others in whom treatment was a component of palliative care. Mean duration of treatment was 3.5 months (range 2 to 6 months). Systemic treatment was averted in 11 patients because response to topical therapy was so favorable, but bone marrow or respiratory failure led to a fatal outcome in 5 other patients. Adverse effects were minimal. One patient developed contact allergy to topical nitrogen mustard after 2 years of intermittent therapy, but was successfully desensitized and was then able to continue treatment. We conclude that the topical application of nitrogen mustard is an effective treatment for cutaneous Langerhans cell histiocytosis. Although adverse effects were minimal in the short term, there remains concern about the possibility of long-term cutaneous carcinogenicity.

Administration, Topical↗
PubMed1991

Partial reversibility of cisplatin nephrotoxicity in children.

To evaluate the long-term renal toxicity of cisplatin, 40 children who had been without treatment at least 18 months (range 18 months to 7 years) were observed. In all the children, glomerular filtration rate (GFR) was estimated from the plasma clearance of chromium 51-labeled ethylenediaminetetraacetic acid, both at the end of treatment and at a median follow-up of 2 years 6 months after treatment was stopped (range 18 months to 7 years). In 21 children, serum magnesium level was also measured at follow-up. Median age at diagnosis was 15 months (range 13 days to 13 years 8 months), and median cumulative doses of cisplatin was 500 mg/m2 (range 120 to 1860 mg/m2). In 22 of 24 children with an end-of-treatment GFR of less than 80 ml/min per 1.73 m2, the median improvement in GFR at follow-up was 22 ml/min per 1.73 m2 (range 2 to 56 ml/min per 1.73 m2). Hypomagnesemia was found in 6 of 21 children and was independent of GFR. No significant correlation was found between improvement in renal function and total cisplatin dose, age, gender, tumor type, or associated nephrotoxic medication. We conclude that most children have some recovery from cisplatin glomerular toxicity, especially if damage is not severe, but that hypomagnesemia may persist.

Adolescent↗
PubMed1991

Hepatopathy-thrombocytopenia syndrome--a complication of dactinomycin therapy for Wilms' tumor: a report from the United Kingdom Childrens Cancer Study Group.

We have observed hepatopathy, associated with thrombocytopenia, in children receiving chemotherapy for Wilms' tumor. We have studied this hepatopathy-thrombocytopenia syndrome (HTS) in patients enrolled in the United Kingdom Childrens' Cancer Study Group (UKCCSG) Wilms' tumor trials (UKW1 and UKW2). At the time of this study, 501 patients had completed therapy. Treatment flow sheets were examined for evidence of hepatopathy (hepatomegaly with abnormal liver function tests) and severe thrombocytopenia (platelet count less than 25 x 10(9)/L). No child who developed the syndrome had received irradiation. HTS was seen in five of 355 (1.4%) of patients treated with combination chemotherapy but in none of the 146 patients treated with vincristine alone. In each instance, the onset was less than 10 weeks after diagnosis. In two children, hepatopathy was severe with jaundice, ascites, transaminases greater than 1,000 IU/L, and prolongation of prothrombin time. On average, HTS lasted 12 days, and resolved with supportive treatment. After recovery, the children tolerated chemotherapy, mostly at reduced dosage, without recurrence. There was no evident long-term morbidity. Dactinomycin is the probable cause of this syndrome. We conclude that the HTS is a rare but important complication of dactinomycin-containing combination chemotherapy for Wilms' tumor. Children developing "isolated" thrombocytopenia following dactinomycin are "at risk" of developing the full-blown syndrome and should have their treatment modified accordingly.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Structural rearrangements of the WT1 gene in Wilms' tumour cells.

We have analysed 55 Wilms' tumour DNAs using the cDNA from the candidate Wilms' predisposition gene, WT1. One tumour, GOS 129, shows a partial homozygous deletion involving only the 3'-most exon of the gene. An adjacent 3' DNA sequence, J7-18, which lies on the same NotI fragment as WT1, is present in GOS 129. Thus, this partial deletion does not extend to the adjacent unmethylated 3' HTF island. These data support the candidature of WT1 as a Wilms' predisposition gene. Tumour GOS 129 has become homozygous as a result of a mitotic recombination event proximal to WT1. Three other tumours showed abnormally sized bands on Southern blot analysis which appear to reflect internal heterozygous rearrangements involving the 5' end of the gene. One of these tumours was from a bilaterally-affected patient and the other 3 were from stage III or IV tumours.

Blotting, Southern↗
PubMed1990

Isolation and regional localisation of DNA sequences from a human chromosome 11-specific cosmid library.

A cosmid library has been prepared in the lorist-B vector from a mouse/human somatic cell hybrid containing region 11q23-11pter as the only human component. This chromosome region is stably maintained in the hybrid as a result of translocation onto one copy of mouse chromosome 13. Individual cosmids containing human DNA were isolated by their ability to hybridise with total human DNA, digested with either HindIII or EcoRI, and 33 individual unique sequences were identified. These fragments were then isolated and subcloned into the bluescribe plasmid vector. Regional localisation of these unique sequences was achieved using a panel of somatic cell hybrids containing different overlapping deletions of chromosome 11. The majority of the 33 mapped sequences derived from the long arm of chromosome 11. Two clones were located within the 11p13-p14 region, which is associated with a predisposition to Wilms' tumour. These probes supplement those already mapped to this chromosome and will assist in the generation of a detailed chromosome 11 linkage map.

Animals↗
PubMed1990

Metastatic neuroblastoma: new abnormalities on bone scintigraphy may not indicate tumour recurrence.

Neuroblastoma is a potentially curable childhood malignancy with survival rates of 20% reported even in advanced disease. Technetium-labelled methylene diphosphonate (Tc99m-MDP) scanning is well established as a method of assessing bone disease. We report four patients, with advanced neuroblastoma in complete or partial remission, in whom new abnormalities on bone scintigraphy were due to benign lesions. Correct management depends on the precise diagnosis of such lesions.

Bone Diseases↗
PubMed1990

Primary malignant liver tumors in childhood: assessment of resectability with high-field MR and comparison with CT.

Nine children (mean age 20 months), with proven primary malignant hepatic tumors have been examined prospectively by high-field magnetic resonance (MR) imaging to assess tumor resectability. All patients had comparative ultrasonography (US), 8 patients had X-Ray computed tomography (CT), and surgical correlation was available in 8 patients. The hepatic and portal veins and the inferior vena cava were visualized in all patients on MR and in 4 of 8 patients on CT. MR accurately defined liver parenchymal involvement in all 8 patients who had surgical exploration. CT underestimated disease in 2 cases, and defined tumour margins less clearly than MR. MR identified abnormal extrahepatic tissue when present, but was unable to distinguish viable tumor from necrotic tumor or reactive nodes. High quality short TR/short TE spin echo images were obtained by combining cardiac triggering and signal averaging. Short TI inversion recovery images demonstrated tumor and lymphadenopathy most clearly. We conclude that MR is the imaging method of choice for the assessment of liver tumor resectability in children.

Child, Preschool↗
PubMed1990

Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome).

The clinicopathologic and radiologic features of 12 children with complete and incomplete forms of Drash syndrome are reported. Their common denominator was a nephropathy. Four had the full triad, consisting of nephropathy, Wilms tumor, and genital abnormalities; five had nephropathy and genital abnormalities, and three had nephropathy and Wilms tumor. Of the 11 children who had proteinuria, eight had the nephrotic syndrome. Of the 10 whose condition progressed to end-stage renal failure, seven were less than 3 years of age. The histologic features of Wilms tumor were favorable in all seven children, and the tumor was bilateral in three. Of the nine patients who had genital abnormalities, eight had 46,XY karyotype and either ambiguous genitalia (six patients) or normal female phenotype (two). One other patient had a normal 46,XX female karyotype and phenotype but had both müllerian and wolffian structures and a streak ovary. Nine patients had a distinct pelvicaliceal abnormality not previously reported as a feature of this syndrome. Other congenital abnormalities were aniridia, mental retardation, deafness, nystagmus, and cleft palate. This syndrome must be considered in any infant with unexplained nephropathy, particularly in young phenotypic female infants and in those children with ambiguous genitalia or Wilms tumor with an early presentation.

Child↗
PubMed1990

'JEB'--a carboplatin based regimen for malignant germ cell tumours in children.

Between February 1986 and July 1988 a total of 21 children aged 1 to 16 years with malignant germ cell tumours (MGCT), 18 with either metastatic disease or unresectable primary tumour, received the JEB regimen - carboplatin dosage calculated from the EDTA glomerular filtration rate (approximately 600 mg m-2), etoposide 120 mg m-2 daily x 3, and bleomycin 15 mg m-2 weekly. Primary sites were: testis (6), ovary (8), sacrococcyx (4), pineal gland (2) and vagina (1). AFP levels were elevated in 19, beta-HCG in 8. Complete marker response was achieved in 19 out of 19 evaluable patients and complete remission of measurable tumour in 16 out of 19, 12 with chemotherapy alone and 4 with the addition of surgery. A reduction in glomerular filtration rate greater than 10% occurred in 3 of 12 evaluable patients; in none greater than 20%. Sequential audiography was normal in 11 out of 12 evaluated. The regimen was myelosuppressive with WHO grade III or IV myelosuppression occurring in 12 patients. Three patients have relapsed; one with a pineal germinoma who relapsed in the abdomen six months after diagnosis, and two with sacrococcygeal teratomas and lung metastases. Two of these remain in second complete remission after further treatment. There was one death from probable bleomycin pulmonary toxicity. We conclude that this regimen is simple to administer and, apart from myelosuppression, it is well tolerated. It appears to have comparable efficacy to cisplatin-based regimens but with much less nephrotoxicity and ototoxicity and avoids the use of alkylating agents and anthracyclines.

Adolescent↗
PubMed1990

Short duration, high dose, alternating chemotherapy in metastatic neuroblastoma. (ENSG 3C induction regimen). The European Neuroblastoma Study Group.

Fifty-one children, aged from 15 months to 13 years 5 months with metastatic neuroblastoma presenting sequentially at the participating institutions received four 3 to 4 weekly courses of high dose multiagent chemotherapy. High dose cisplatin (200 mg m-2) combined with etoposide (500 mg m-2), HIPE, was alternated with ifosfamide (9 g m-2), vincristine (1.5 mg m-2), and adriamycin (60 mg m-1), IVAd. Disease status was re-evaluated 3 to 4 weeks after the fourth course and the response classified according to the International Neuroblastoma Response Criteria (INRC). The overall response rate in evaluable patients was 55% and response rates by site were: bone marrow 67% (complete response 47%); bone scan 68%; primary tumour 61%, and urinary catecholamine metabolites (VMA/HVA) 95%. Serial 51Cr EDTA renal clearance studies showed a glomerular filtration rate (GFR) decline in 40% of patients but in only seven cases to below 50% of the pretreatment value. There was no instance of renal failure during induction, though two patients developed severe renal failure following 'megatherapy' given to consolidate remission. Serial audiometry showed a significant decline in hearing at frequencies above 2,000 Hz in 37% of children but at or below 2,000 Hz in only 17%. Neutropenia and thrombocytopenia were severe and intravenous antibiotics were required after 30% of courses. Each of two treatment-related deaths occurred during pancytopenia following courses of IVAd. Complete, or greater than 90%, removal of primary site tumour was possible in 70% of cases following this induction regimen and 75% of patients proceeded to elective megatherapy within a median time of 24 weeks after diagnosis. This short intensive induction programme is highly effective at achieving cytoreduction, enabling early surgery and early megatherapy procedures. It is, however, too early to draw firm conclusions about the impact of this approach to treatment on the cure rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Path of bullet and injuries determined by radiography.

Radiography is commonly used to find bullet pathways in forensic pathology. In the case presented here, a man had sustained multiple gunshot wounds and one bullet could not be traced. A radiograph was used to find the bullet and showed an interesting bullet pathway. By observing the bullet pathway on a radiograph, sometimes we can surmise the victim's body posture at the time of an incident.

Firearms↗
PubMed1990

Biophysics of the inhibition of the growth of maize roots by lowered temperature.

Roots of hydroponically grown maize (Zea mays cv LG11) have a greatly reduced growth rate at 5 degrees C (0.02 millimeters per hour) compared with those at 20 degrees C (1.2 millimeters per hour). Various physical parameters of roots growing at each temperature were compared. Turgor pressure of cells in the elongation zone increased from 0.59 +/- 0.05 megapascal at 20 degrees C to 0.82 +/- 0.04 megapascal after 70 hours at 5 degrees C; thus, growth rate was not limited by decreased pressure. On cooling, tissue plasticity (measured by Instron/tensiometer) decreased slowly over 70 hours. On rewarming to 20 degrees C from 5 degrees C, growth rate, turgor pressure, and tissue plasticity all returned concertedly to their original values over a period of days. However, immediately following cooling growth rate dropped rapidly from 1.8 to 0.12 millimeters per hour in 30 minutes but turgor pressure and tissue Instron plasticity remained unchanged. A plot of turgor pressure against growth rate indicated that, following cooling from 30 to 15 degrees C, the in vivo wall extensibility of the tissue was reduced by 75%. Yield threshold was unchanged. Cells whose expansion was arrested in the long-term cold treatment do not resume growth. Root growth recovers by the expansion of cells newly produced by the meristem. Cessation of extension growth is an effect on the individual expanding cell. Growth recovery is not a reverse of this effect but requires the generation of fresh cells.

Journal Article↗
PubMed1990

Increased endogenous abscisic Acid maintains primary root growth and inhibits shoot growth of maize seedlings at low water potentials.

Roots of maize (Zea mays L.) seedlings continue to grow at low water potentials that cause complete inhibition of shoot growth. In this study, we have investigated the role of abscisic acid (ABA) in this differential growth sensitivity by manipulating endogenous ABA levels as an alternative to external applications of the hormone. An inhibitor of carotenoid biosynthesis (fluridone) and a mutant deficient in carotenoid biosynthesis (vp 5) were used to reduce the endogenous ABA content in the growing zones of the primary root and shoot at low water potentials. Experiments were performed on 30 to 60 hour old seedlings that were transplanted into vermiculite which had been preadjusted to water potentials of approximately -1.6 megapascals (roots) or -0.3 megapascals (shoots). Growth occurred in the dark at near-saturation humidity. Results of experiments using the inhibitor and mutant approaches were very similar. Reduced ABA content by either method was associated with inhibition of root elongation and promotion of shoot elongation at low water potentials, compared to untreated and wild-type seedlings at the same water potential. Elongation rates and ABA contents at high water potential were little affected. The inhibition of shoot elongation at low water potential was completely prevented in fluridone-treated seedlings during the first five hours after transplanting. The results indicate that ABA accumulation plays direct roles in both the maintenance of primary root elongation and the inhibition of shoot elongation at low water potentials.

Journal Article↗
PubMed1990

Re-expression of Nerve Growth Factor Receptor after Axonal Injury Recapitulates a Developmental Event in Motor Neurons: Differential Regulation when Regeneration is Allowed or Prevented.

Motor neurons in the brainstem and spinal cord transiently express nerve growth factor receptors (NGFr) during development, but not in normal adult animals. In this study, NGFr was immunohistochemically identified in hypoglossal motor neurons after different types of peripheral axonal injury in adult rats. NGFr is re-expressed in motor neurons 7 days after a nerve crush injury, and has disappeared again by 28 days. These times correspond, respectively, to the active phase of regeneration, and a time by which regeneration has largely been completed, as determined by electrical activation of tongue muscle twitch. In contrast, 7 days after nerve transection and ligation of the proximal stump to prevent regeneration, there is no re-expression of NGFr, but 28 days after such treatment NGFr is present in a few neurons. By this time, neuroma formation has begun proximal to the end of the cut and ligated nerve. Together, these findings suggest that motor neurons transiently re-express NGFr during regeneration and not in response to axonal transection per se. The signal triggering re-expression thus seems more likely to be the introduction of a message from the site of injury, rather than the loss of a target-derived message. Although the function of NGFr in developing and regenerating motor neurons is not known, its expression appears to be associated with periods of axonal growth and maturation.

Journal Article↗
PubMed1990

Langerhans cell histiocytosis: the case for conservative treatment.

Fifty eight children with Langerhans cell histiocytosis who were referred to this hospital between 1980 and 1987 were studied. Fourteen had single system disease, and 44 had multisystem disease, of whom 22 had vital organ dysfunction. A conservative approach to treatment was adopted, and when systemic treatment was indicated a short course of prednisolone was used first. Eight of the patients with single system disease required no treatment, while six received local treatment alone. Eight of the patients with multisystem disease did not require systemic treatment, 17 were given prednisolone alone, and 19 were given cytotoxic drugs. Of the 14 with single system disease 13 had no long term after effects. Eight of the patients with multisystem disease died, 24 had long term after effects, and 12 had none. Outcome was related to age and Lahey score. These results compare favourably with other series in which more aggressive approaches were used, and support our conservative approach to treatment.

Adolescent↗