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Biomedical subjects

R F Carter

Publications and source records attributed to R F Carter.

At least 37 records · Page 2Linked to original sources
PubMed1990

Pathology of hepatic peroxisomes and mitochondria in patients with peroxisomal disorders.

The morphology of hepatic peroxisomes in five patients with metabolic disorders believed to be due to inherited defects of peroxisomal function or biogenesis is described. Electron microscopy and cytochemical staining for catalase were used to identify peroxisomes in two boys with infantile Refsum's disease (IRD), a girl with autopsy confirmed neonatal adrenoleukodystrophy (NALD), and two boys with pseudo-Zellweger syndrome (PZS). In the patients with IRD and NALD hepatic peroxisomes were significantly reduced in size and number and contained electron dense centres. In the liver of the patients with PZS the peroxisomes were enlarged. Morphologically abnormal peroxisomes were also detected in autopsy tissue from one boy with PZS using electron microscopy. Lamellar-lipid inclusions and mitochondria with crystalline inclusions and/or abnormal cristae are also described in two patients, one with IRD, the other with NALD.

Adrenoleukodystrophy↗
PubMed1990

Laboratory abnormalities in patients with cancer.

In this problem-oriented review of abnormalities associated with cancer, we have emphasized distinctive diagnostic points related to pathogenesis for each condition and outlined how the approach to management is determined by pathogenesis. For abnormalities of the complete blood count, it is important to distinguish between abnormalities directly related to marrow malignancy and abnormalities associated with extramarrow malignancy. Hemopoietic tumors consist of developmentally deficient blood cells produced by a clonal population of malignant stem cells. Tumors infiltrating marrow cause overcrowding in the limited marrow microenviroment. Extramarrow malignancies cause blood abnormalities, but the potential for normal marrow function is present. Abnormalities of blood cells secondary to therapy are usually clearly identified by consideration of clinical history. The initial differential diagnosis for hypercalcemia is malignancy. An aggressive diagnostic approach may be needed to identify the neoplasm, and therapy should incorporate measures to prevent renal failure. Hypoproteinemia and hyperproteinemia may be caused by neoplasia. Monoclonal gammopathies should be identified and may be associated with hyperviscosity syndrome. Hypoglycemia in the adult animal is most frequently caused by insulin-secreting tumors, but it has also been associated with hepatic and other tumors. Increased blood urea nitrogen, creatinine, lipase, amylase, and liver enzyme activities may also be caused by malignancy. Inadequate urine concentrating ability may be caused by hypercalcemia or malignancy-associated renal insufficiency. Hematuria in older animals is suggestive of urinary tract neoplasia. Exfoliated tumor cells may be identified in the urine sediment of these patients.

Animals↗
PubMed1990

Clinical management of the cancer patient. Taking a biopsy.

Good biopsy protocol depends on excellent interaction with diagnostic pathologists. This article reviews the essentials of diagnostic appraisal, specimen preparation, biopsy interpretation, proper reporting, and implementation of biopsy results in case management. The emphasis is on biopsy of malignancy.

Animals↗
PubMed1990

Chromosome abnormalities in chronic myeloid leukaemia. A model for acquired chromosome changes in haematological malignancy.

The last decade has been very exciting for cancer cytogeneticists. At the start of the decade, the role of cytogenetics in clinical medicine was still unclear. Many felt that such investigations were largely of academic interest. Today, cytogenetic investigations are considered essential in many cancers, where they contribute in diagnosis, staging, choice of therapeutic protocol, and monitoring of the effects of therapy. The number of primary chromosome changes in human cancer exceeds 100, and while the majority of these changes are associated with haematological malignancies, the contribution from the solid tumours is now growing rapidly. Closer ties between scientists and physicians involved in laboratory and clinical medicine have resulted in the emergence of many well-defined cytogenetic-clinicopathological entities. With the advances in molecular biology that characterized the 1980s came the disappearance of all scepticism about the critical role played by chromosome change in oncogenesis. To date, we have learned more about the details of cancer biology in chronic myeloid leukaemia and the lymphoid malignancies through the molecular dissection of primary chromosome changes than through any other approach. Further studies will, no doubt, lead us to an understanding of the molecular basis of many of the primary and secondary chromosome changes that are non-randomly acquired in human cancer.

Chromosome Aberrations↗
PubMed1990

Long-term culture of canine marrow: cytogenetic evaluation of purging of lymphoma and leukemia.

We established and maintained long-term cultures of marrow from normal dogs and dogs with lymphoma or leukemia by single inoculations of mononuclear cell suspensions. Media containing only horse sera (as opposed to horse and fetal calf sera) and catalase (for antioxidative effect) supported improved culture viability, as indicated by increased recovery of progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) and the release of abundant erythroid cells in the cultures for up to 3 weeks. CFU-GM were maintained for at least 3-4 weeks of culture. Culture appearance, cell counts, and assays of CFU-GM were used to compare the culture kinetics of tumor-involved marrow to normal marrow specimens. Cultures of marrow with extensive tumor involvement tended to be less viable, apparently due to a relative lack of competent progenitors. To investigate whether canine long-term marrow culture provided a purging effect similar to the loss of tumor cells noted in human long-term cultures of marrow from patients with chronic myelogenous leukemia (CML) or acute myelogenous leukemia (AML), we established long-term marrow cultures from 28 dogs with histologically confirmed untreated lymphoma or leukemia. Eleven of these dogs had cytogenetically marked tumor cells in the marrow at the initiation of culture. In six dogs with lymphoma and one dog with acute monocytic leukemia (AMoL) French-American-British classification (FAB) M4 leukemia, we could detect no cytogenetic evidence for persistence of the tumor clones in individually plucked or pooled CFU-GM grown from 3-week-old long-term cultures. In one case of AML (FAB M2), 80% of CFU-GM recovered from long-term cultures at 4 weeks still contained an extra metacentric marker chromosome associated with the continued presence of the leukemic clone in the cultures. Our documentation of a purging effect for some tumors supports the use of this canine model system in the investigation of autologous marrow transplantation with long-term cultured cells for humans with lymphoma and leukemia.

Animals↗
PubMed1988

Depression of immunity to Naegleria fowleri in mice by selective depletion of neutrophils with a monoclonal antibody.

In an attempt to define the role of neutrophils in immunity to Naegleria fowleri in vivo, we examined the effects of treating immunized (with amoeba culture supernatant antigen) mice with the monoclonal antibody NIMP-R10, which binds to neutrophil complement receptor type 3bi (CR3) and causes selective neutrophil depletion in mice. Mice in the nonimmunized group challenged with amoebae all died by day 12, while 97% in the immunized group survived. By contrast, the immunized group treated with NIMP-R10 showed only 25% survival. The immunized group treated with "control" mouse ascites, WEM-G11, was highly resistant (90% survival). There was a significant neutrophil response in the nasal mucosa and olfactory lobes of immunized, NIMP-R10-treated mice, despite a marked degree of neutropenia similar to that seen in immunized, untreated mice. Nonimmunized mice showed virtually no neutrophil response. Despite this response in the NIMP-R10-treated mice, amoebic proliferation was not depressed, and there was no evidence of neutrophil degranulation or amoebic killing, despite the close apposition of large numbers of neutrophils to amoebae. The results indicate that neutrophils are necessary for the expression of immunity to N. fowleri.

Agranulocytosis↗
PubMed1987

A fertile man with tdic(Y;22): how a stable neo-X1X2Y sex-determining mechanism could evolve in man.

We describe a normal man with the karyotype: 45,X,dic(Y;22)(Ypter----Yq11.23::22p11.2----22qter+ ++). A brother and father of the propositus also had 45 chromosomes with the same dic(Y;22). Carriers of this chromosome are of normal phenotype, and the carrier of reproductive age had apparently normal fertility. A neo-X1X1X2X2/X1X2Y sex-determining mechanism can be considered to be operating in this family.

Chromosome Deletion↗
PubMed1987

Somatostatin, anaesthesia, and the carcinoid syndrome. Peri-operative administration of a somatostatin analogue to suppress carcinoid tumour activity.

A patient with carcinoid syndrome on long-term antiserotonin therapy with parachlorophenylalanine, experienced a flushing attack with hypotension during the prophylactic administration of aprotonin prior to the induction of anaesthesia. When she was subsequently prepared with a long-acting somatostatin analogue, octreotide (Sandostatin, Sandoz SMS 201-995), plasma levels of tumour-released hormones were reduced and anaesthesia for resection of hepatic metastases was uneventful. The advantages of an anaesthetic approach based on inhibition of carcinoid tumour activity, rather than antagonism of released hormones, are discussed.

Anesthesia, General↗
PubMed1986

Two-year experience of management of bleeding esophageal varices with a coordinated treatment program based on injection sclerotherapy.

The results of 61 consecutive patients treated for bleeding esophageal varices with a coordinated multidisciplinary protocol are described. The primary form of treatment after vigorous resuscitation was fiberoptic endoscopic injection sclerotherapy under general anesthetic. Thirteen patients failed to be controlled by injection, and eight were able to be treated by percutaneous transhepatic embolization. Those patients who were unable to undergo embolization or whose bleeding did not stop after embolization were controlled by surgery. The overall mortality rate with the 2-year limit was 29 patients (47%); however, only 18 deaths (29%) were related to the hospital admission for bleeding. Only one patient died of continued variceal bleeding. All of the other deaths were from later liver failure or unrelated disease. The results of the study confirmed the high mortality rate in patients with severe liver disease (Child's grade C) undergoing surgical control of bleeding, and it was shown that when control was obtained with injection sclerotherapy and embolization, the 1-year survival rate of a similar group of patients may be as high as 32%.

Anesthesia, General↗
PubMed1986

The cytology, histology and prevalence of cell types in canine lymphoma classified according to the National Cancer Institute Working Formulation.

No significance has been shown yet between the cytological subtypes of canine lymphoma and clinical behaviour. This paper describes and illustrates the cytological and histological criteria for application of the National Cancer Institute Working Formulation classification system, a scheme with demonstrated prognostic capability for human non-Hodgkin's lymphomas, to a series of 285 canine lymphomas. The Working Formulation can be used without difficulty for canine lymphomas. Low grade follicular tumors were found to be much less common, and high grade, aggressive tumors much more common than these cell types in humans. Low grade tumors tend to have low mitotic rates and high grade tumors tend to have high mitotic rates. There may be an association between hypercalcemia and lymphoblastic cell type. A review of available literature data for canine lymphomas suggests that prognostic extrapolation of clinical behaviour based on human lymphoma data may be possible. These results suggest that there may be strong similarities of morphology and behaviour between human non-Hodgkin's lymphomas and canine lymphomas.

Animals↗
PubMed1985

Legal and scientific probability of causation of cancer and other environmental disease in individuals.

How to evaluate and apply probabilistic scientific evidence that cancer (or other diseases) have been caused by chemical substances (or other environmental agents) constitutes a critical problem which must be addressed by legal institutions. This article analyzes the basis of the current scientific concepts of causation and the means of incorporating epidemiological and statistical evidence of causation into the legal process, primarily with respect to cases of harm to individuals. Experiments with and adjustments of the legal system to effect an adequate accommodation of such probabilistic evidence are suggested.

Biological Assay↗
PubMed1985

Infantile Refsum's disease: a peroxisomal storage disorder?

An 18-month-old infant presented with a history of arrest of neurological development from the age of eight months, with progressive ataxia, deafness, retinitis pigmentosa and hepatomegaly. Biochemical investigations revealed an elevated plasma phytanic acid level and deficiency of phytanic acid oxidase in skin fibroblasts. Histopathological findings in a liver biopsy were similar to those reported in infantile phytanic acid storage disease. Unexpected findings were the presence of elevated levels of plasma pipecolic acid, and elevated plasma long-chain fatty acid ratios, biochemical findings previously considered to be diagnostic of Zellweger's hepato-cerebro-renal syndrome, and of adrenoleucodystrophy, respectively. Recent biochemical evidence suggests that this patient, and other similar cases that have recently come to our attention, may have a fundamental defect in the peroxisomal enzyme system.

Age Factors↗
PubMed1984

Lipopolysaccharide hyperreactivity of animals infected with Trypanosoma lewisi or Trypanosoma musculi.

Rats and mice infected with Trypanosoma lewisi and Trypanosoma musculi, respectively, showed hyperreactivity to lipopolysaccharide (LPS) from gram-negative bacteria. Fatal shock could be precipitated with a dose of LPS 100 to 1,000 times less in infected compared with noninfected animals. In trypanosome-infected rats and mice, extensive liver damage was evident after LPS challenge. These animals showed a pronounced hypoglycemia, marked elevation of blood aspartate transaminase level, and diffuse severe degeneration and total depletion of glycogen in hepatocytes. Only minor changes were observed in noninfected animals given the same dose of LPS. No mononuclear phagocytic cell infiltration was observed in the liver of infected animals. The most striking change was the great increase in size and the probable increase in phagocytic activity and number of sinusoidal Kupffer cells. We suggest that elevated Kupffer cell activity in trypanosome-infected animals may play a role in LPS-induced hepatotoxicity.

Animals↗
PubMed1984

Simultaneous on-line measurement of blood K+, Ca2+, Na+, and pH with a four-function ChemFET integrated-circuit sensor.

On-line, simultaneous measurement of blood K+, Ca2+, Na+, and pH has been achieved by using a quadruple-function ChemFET (chemical-sensitive field-effect transistor) integrated-circuit sensor. Blood is withdrawn from the subject through an actively heparinized, dual-lumen cannula and passed into a flow-cell containing the sensor, in alternation with a calibration solution. A minicomputer controls the analysis system, logs data, and provides a continuous, graphic display of K+ and pH values.

Autoanalysis↗