Chronic disease prevention among minority groups: problems and possibilities.
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Chronic Disease↗
Biomedical subjects
E Harvey
Publications and source records attributed to E Harvey.
Maintaining quality in blood banking.
Regulation of transfusion or blood banking facilities has followed, rather than preceded the regulation of the pharmaceutical industry and today we find, in Europe and the United States, the basic regulations developed for the pharmaceutical industry being extended to blood transfusion centres (BTC)*. In this article we explore the role of voluntary accreditation or registration to quality systems standards such as ISO 9000 and discuss how these can be used to advantage and how these standards can provide a substantial base for meeting legislative requirements. In the UK there is also a voluntary accreditation procedure available for all clinical laboratories, known as Clinical Pathology Accreditation (CPA). Comparisons between ISO 9000, CPA and other standards are made. We also discuss how voluntary registration, particularly to ISO 9000 can provide an excellent basis for moving into more extensive and progressive Total Quality Management (TQM) programmes which in turn bring a variety of benefits, not least of which is increased staff involvement in your organisation. Experience of the route to quality through voluntary accreditation suggests that external assessment delivers new insights into the organisation that cannot easily be supplanted by internal audit. In Europe legislation relating to pharmaceuticals has steadily increased in scope and in detailed requirements from those set out in the 1965 Directive 65/65/EEC. The legislative framework has steadily increased, bringing plasma and plasma products as well as others such as radiopharmaceuticals, into the product licensing requirements. The progression of legislation seems unlikely to cease and it is debatable how long the Medicines Control Agency (MCA) and its Inspectorate will accept that BTCs can operate at a level which is different from that of the majority of pharmaceutical manufacturers. The change in emphasis in legislation particularly in Europe means that harm that is caused to a patient by a blood component will warrant redress. The degree of fault attributed to the producer will in part depend on whether they have met the best available standards at all stages in the preparation of the product. If a Transfusion Service can show that it's operation has external accreditation, particularly to an internationally recognised standard such as ISO 9000 and they can show that staff have been properly trained, that equipment is properly supplied and maintained and that the facility is appropriate to the work being carried out, then the liability that exists when something goes wrong will be reduced.(ABSTRACT TRUNCATED AT 400 WORDS)
Accreditation↗
The molecular epidemiology of human immunodeficiency virus type 1 in Edinburgh.
Human immunodeficiency virus (HIV) type 1 sequences obtained from HIV-infected persons in different risk groups in Edinburgh were studied to determine the number and origin of virus variants and patterns of virus transmission. Phylogenetic analysis revealed that 12 of 14 hemophiliac patients who had been exposed to a single common batch of factor VIII had closely related gag gene sequences. Sequences from intravenous drug users and patients infected through heterosexual contact formed another distinct group, and 2 other hemophiliacs formed a third group. However, epidemiologic relationships inferred from analysis of the V3 region of the env gene were less conclusive, especially when the V3 loop was taken in isolation. This appears to be due to the length of time since infection and the action of selection, which has favored the independent appearance of similar V3 loop variants.
Base Sequence↗
Urinary 3 alpha,17 beta-androstanediol glucuronide is a measure of androgenic status in Eld's deer stags (Cervus eldi thamin).
To determine the primary excretory by-products of testosterone (T), 85 microCi [3H]T was administered i.v. to two adult Eld's deer stags. Blood (10 ml) was collected by jugular venipuncture at 0, 5, 10, 15, 30, 45, 60, 90, 120, 150, 180, 240, and 480 min after isotope infusion, and all urine and feces were collected for 96 h after injection. Seventy percent of labeled circulating steroid was conjugated by 30 min postinfusion. The majority (80.4 +/- 3.2%) of T metabolites were excreted into urine, and 95.0 +/- 0.9% of these were conjugated, 95.8 +/- 0.2% being hydrolyzable with glucuronidase. Seven urinary androgen metabolites, including androstanediol (5 alpha-androstan-3 alpha-17 beta-diol and 5 beta-androstan-3 alpha-17 beta-diol), were identified in glucoronidase-hydrolyzed, ether-extracted Eld's deer urine pools after gas chromatography/mass spectrometry. A double-antibody 125I RIA for 5 alpha-androstanediol-3 alpha, 17 beta-diol,17-glucuronide (3 alpha-diol-G) was validated for unprocessed urine. Longitudinal assessments of urine samples collected from 13 stages for 3 yr revealed biological concordance between fluctuations in urinary 3 alpha-diol-G and serum T, as well as seasonal changes in secondary sexual characteristics. Overall correlation between "same-day" matched serum T and urinary 3 alpha-diol-G was 0.58, (n = 6; p < 0.001). Thus, monitoring urinary 3 alpha-diol-G provides a noninvasive, alternative method for characterizing male endocrine interrelationships in an endangered ungulate species.
Androgens↗
The personal experiences of a nurse in England, 1938-1974.
These recollections trace the experiences of a school nurse working in the East End of London from 1938 to 1974. They include a brief history of Stepney and the Docklands, the ethnic mix and the social and economic conditions before the war. They describe the effects of World War II with the bombing and its devastation and the evacuation of children to the country, their return and forced re-evacuation, and the effect on the children. After the war the recollections recount the continuing struggle with health education as a health visitor and something of the post-war reconstruction.
Health Education↗
Joubert syndrome with congenital hepatic fibrosis: an entity in the spectrum of oculo-encephalo-hepato-renal disorders.
Joubert syndrome is an autosomal recessive inherited condition characterized by agenesis or hypoplasia of the cerebellar vermis, retinal dystrophy, chorioretinal colobomata, oculomotor abnormalities, episodic hyperpnea, ataxia, and mental retardation. Congenital hepatic fibrosis has not previously been described in Joubert syndrome. We report two unrelated children with Joubert syndrome and hepatosplenomegaly. On histopathological examination, both had congenital hepatic fibrosis. Both were also found to have congenital medullary cystic disease of the kidneys. Joubert syndrome appears to be one of a spectrum of congenital malformation syndromes involving the central nervous system, eye, liver and kidneys.
Abnormalities, Multiple↗
Acute tumour lysis syndrome with no evidence of tumour load.
Acute tumour lysis syndrome (ATLS) is a well-recognised complication of the treatment of a variety of malignant disorders in which a large mass of disease is obvious. ATLS may, however, occur even in the absence of bulk disease. We present two cases which, together with a review of previously reported cases, suggest that a cause of this rare phenomenon is primary renal lymphoma which subsequently develops into the leukaemic phase. This is supported by the observation that some bone marrow aspirates which are normal at the time of ATLS have shortly afterwards demonstrated lymphoblasts. Renal biopsy may not exclude primary lymphoma of the kidney. In excluding lymphoproliferative disease in the differential diagnosis of acute hyperuricaemia, the importance not only of bone marrow examination but of exhaustive investigation of the kidneys is stressed.
Acute Disease↗
rhGM-CSF ameliorates neutropenia in patients with malignant glioma treated with BCNU.
Nitrosoureas are the drugs most effective in the treatment of patients with intracerebral malignant glioma. Their limiting toxicity is delayed myelosuppression. A prospective, randomised crossover study of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was performed in patients receiving BCNU for relapsed glioblastoma, to investigate whether the resulting haematological toxicity profile could be modified by rhGM-CSF. Adequate data for analysis were obtained in 13 patients. Following BCNU, the nadir neutrophil count was higher in 12 out of 13 patients during the rhGM-CSF-protected cycles compared with the unprotected cycles. The median nadir was also significantly higher (1.79, CI 0.76-3.52, P < 0.005). Five episodes of neutropenia (< 2 x 10(9) l-1) occurred during the unprotected cycles compared with none in the rhGM-CSF-protected cycles (P = 0.076). There was no evidence of any effect on platelets. This result shows that the haematological toxicity profile following therapeutic doses of BCNU can be modified. It suggests that rhGM-CSF and other growth factors should be investigated for clinical efficacy in chemotherapy using nitrosoureas.
Adult↗
Phase II multicenter evaluation of prolonged murine monoclonal antibody 17-1A therapy in pancreatic carcinoma.
Twenty-eight patients with unresectable, measurable pancreatic carcinoma and Eastern Oncology Cooperative Group (ECOG) performance status of 0 or 1 were treated with the murine monoclonal antibody 17-1A, planning to administer 500 mg i.v. three times weekly for 8 weeks. Treatment was well tolerated, with an 18% incidence (five patients) of hypersensitivity reactions. All hypersensitivity episodes occurred in the first 3 weeks of therapy and required treatment discontinuation. Six patients required early discontinuation of therapy due to symptomatic progressive disease and one patient was removed from the study due to a protocol violation. Sixteen patients received the full course of 12 g of antibody. One patient has exhibited a durable partial response. Antibody pharmacokinetics were determined in five patients. In four patients peak 17-1A levels averaged 100 micrograms/ml with mean harmonic t1/2 of 16.8 h in a one-compartment model. Neither pretreatment nor posttreatment levels of circulating 17-1A changed significantly during the 8 weeks of treatment. This study demonstrates the feasibility and acceptable toxicity of repetitive dosing with an unconjugated murine monoclonal antibody. The lack of efficacy of treatment suggests that factors other than prolonged exposure of tumor and cytotoxic effector cells to murine antibody are required for successful antibody therapy of pancreatic cancer.
Aged↗
A pilot study of low-dose recombinant human granulocyte-macrophage colony-stimulating factor in chronic neutropenia.
Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) is under investigation for the treatment of a wide range of haematological disorders. At commonly used doses of > 120 micrograms/m2/d, extramedullary toxicity is common. We report the effects of low-dose (LD) rhGM-CSF in patients with chronic neutropenia related to HIV infection, myelodysplastic syndrome and idiopathic neutropenia. Nine patients with a mean pre-treatment neutrophil count of 0.6 x 10(9)/l (range 0.2-1.4 x 10(9)/l) received daily rhGM-CSF at doses of between 5 and 15 micrograms/m2. Eight patients responded with a mean post-treatment ANC of 3.2 x 10(9)/l (range 1.9-4.6 x 10(9)/l). There was no significant therapy-related morbidity. We conclude that in chronic neutropenia, LD rhGM-CSF is an acceptable treatment which has important cost/benefit implications.
Adult↗
Rapid development of an immunoblastic lymphoma and death in children following cadaveric renal transplantation.
We report on three children who underwent cadaveric renal transplantation and subsequently developed an immunoblastic lymphoma, leading to death in two patients. The development of the lymphoma occurred following a multi-drug immunosuppression regimen ending with monoclonal antilymphocyte (OKT3) treatment for biopsy-proven cellular and vascular acute rejection. These patients represent three of 11 children who received OKT3 treatment for rejection in the last 18 months at this institution. Following the diagnosis of lymphoma, all three patients were treated by transplant nephrectomy, cessation of immunosuppression, and administration of intravenous acyclovir. The first two patients died at 4 days and 4 weeks, respectively, after the definitive diagnosis was made with widespread metastatic disease. The remaining child is a short-term survivor (13 months), free of demonstrable malignancy. Multidrug regimens for immunosuppression have a profound effects on T cell function. These effects, when combined with a primary infection by the Epstein-Barr virus, are implicated in the rapid development of the lymphomas and are responsible for the death of these two children.
Cadaver↗
Pseudoporphyria cutanea tarda: two case reports on children receiving peritoneal dialysis and erythropoietin therapy.
Pseudoporphyria cutanea tarda occurred in two children undergoing peritoneal dialysis and receiving erythropoietin therapy. The mechanism whereby erythropoietin might lead to photosensitization is unknown, but physicians should be aware of this possible association.
Child↗
Gastrointestinal complications of gastrocystoplasty.
The cases are reported of five children with chronic renal failure who underwent gastrocystoplasty for a variety of urological disorders. Gastrocystoplasty comprises the transplantation of a vascularised segment of stomach to the bladder to form an augmented neobladder. The patients had gastrointestinal complications after the operation, including considerable weight loss in all five patients, accompanied by marked failure to thrive in four of the five patients, and food aversion, feeding intolerance, dumping syndrome, delayed gastric emptying, and oesophagitis in two patients. Three of the five patients developed severe abdominal pain and haemorrhagic cystitis secondary to gastric acid secretion in the neobladder from the transplanted gastric pedicle. Nutritional and pharmacological interventions were used to manage the gastrointestinal problems. Explanations are offered for the pathophysiology of the observed complications of gastrocystoplasty. It is believed that the use of this procedure in infants and children, particularly those with chronic renal failure and uraemia, warrants caution until successful long term follow up and experience with this procedure have been reported.
Abdominal Pain↗
Differential effects of CD45 CD45R and CD45R0 monoclonal antibodies in modulating human B cell activation.
We have examined the effect of monoclonal antibodies (MoAbs) to different epitopes of the leucocyte common antigen (LCA), CD45, on anti-human immunoglobulin-primed B cell activation. Binding of MoAbs to restricted epitopes present on CD45 glycoproteins of 180 kD and 220 kD (designated CD45R0 and CD45R, respectively) was found to promote B cell proliferation in the presence of T cells. CD45 MoAbs reactive with 'public' determinants on all four constituent members of the LCA family (180, 190, 205, and 220 kD) had either little effect or inhibited the basal B cell response to anti-immunoglobulin priming. Simultaneous immunofluorescent analysis of 5-bromodeoxyuridine incorporation and the expression of CD19 (B cell specific) or CD2 (T cell specific) identified the majority of responder cells as B lymphocytes. CD45R MoAbs significantly enhanced the B cell response to sub-optimal concentrations of interleukin-2. CD45 and CD45R0 MoAbs failed to elicit a similar response. Antibody to the interleukin-2 receptor (anti-Tac) partially blocked the CD45R-driven, T cell-dependent B cell proliferation.
Antibodies, Monoclonal↗
Is sequential use of ALG and OKT3 in renal transplants associated with an increased incidence of fulminant posttransplant lymphoproliferative disorder?
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Age Factors↗
Phase II trial of interferon gamma and monoclonal antibody 17-1A in pancreatic cancer: biologic and clinical effects.
Thirty patients with advanced measurable pancreatic adenocarcinoma were entered onto a phase II trial with recombinant interferon gamma (Biogen, Cambridge, MA; 10(6) U/m2 daily for 4 days) and monoclonal antibody (Mab) 17-1A (Centocor, Malvern, PA; 150 mg in autologous leukocytes on days 2, 3, and 4 following interferon infusion). The effect of a single interferon gamma treatment on natural and antibody-dependent cellular cytotoxicity (ADCC), Fc receptor occupancy by antibody, and human leukocyte antigen-DR (HLA-DR) expression on monocytes and lymphocytes was also studied. Toxicity was modest and generally limited to grade I to II fever, nausea and vomiting, and hepatotoxicity. Five patients were considered to be nonassessable for response. Of the 25 assessable patients, one objective response (complete remission for a duration of 4 months) was observed. Stable disease for 2 months or greater was noted in nine patients. The median survival for the group was 5 months. Analysis of cytotoxicity data obtained prior to treatment showed reduced natural cytotoxic activity in these patients compared with normal volunteers. A significant improvement in natural cytotoxic activity to normal levels occurred within 24 hours following the interferon gamma infusion. This was also associated with augmented antibody-dependent cellular cytotoxicity. Although HLA-DR expression was not increased on either monocytes or lymphocytes, an increased capacity of both lymphocytes and monocytes to bind Mab 17-1A was observed. In all in vitro assays of ADCC, the presence of antibody excess was associated with improved cytolytic activity. In spite of the favorable modulation of cytolytic activity and improved ability of effector cells to bind Mab, we failed to demonstrated adequate clinical efficacy in the treatment of patients with pancreatic adenocarcinoma using this dose and schedule of interferon gamma and Mab 17-1A. Future trials will focus on alternate schedules of Mab 17-1A with the hope of improving tumor antigen saturation and circulating levels of infused antibody.
Adenocarcinoma↗
Acute changes in renal function associated with deferoxamine therapy.
In three patients who received intravenous deferoxamine there was a twofold to eightfold increase in plasma creatinine level and a parallel decrease in creatinine clearance that resolved when treatment with the drug was discontinued. In two thalassemic patients, diuresis was evident by urine output exceeding fluid intake. The mechanism was studied in dogs that exhibited an acute and significant decrease in inulin and para-aminohippuric acid clearances induced by intravenous deferoxamine. Saline diuresis could prevent the decrease in the glomerular filtration rate but not the decrease in renal blood flow caused by deferoxamine. Deferoxamine induced an acute increase in the fractional excretion of sodium, potassium, chloride, phosphate, and urate, which may explain the relative diuresis observed in two of the patients. In a subsequent experiment, ferrioxamine induced an increase in the fractional excretion of sodium and chloride but did not affect the glomerular filtration rate and renal blood flow. Our studies suggest that adequate hydration may be needed to preserve renal hemodynamics during intravenous deferoxamine therapy. Repeated measurements of renal function should accompany treatment with this agent.
Adolescent↗
Ocular blood flow in dogs using radiolabelled microspheres.
We used radioactive microspheres of different sizes to determine the rate of blood flow through the various parts of the eye in dogs. The use of either 15 +/- 5 microns or 25 +/- 5 microns microspheres gave reproducible measurements of total ocular and uveal blood flows. Using these sphere sizes, retinal flow was found to be close to 1% of the total ocular blood flow and showed poor reproducibility due in part to the small number of spheres trapped in the retinal vessels.
Animals↗