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Biomedical subjects

J C Graham

Publications and source records attributed to J C Graham.

At least 37 records · Page 2Linked to original sources

Immunohistochemical assay for detecting estrogen receptors in canine mammary tumors.

OBJECTIVE: To determine the estrogen receptor (ER) content of canine mammary gland tumors by use of immunohistochemical (IHC) examination of formalin-fixed sections. SAMPLE POPULATION: 21 mammary gland tumors from 20 adult dogs. PROCEDURE: ER were detected in formalin-fixed tissues, using an avidin-biotin alkaline phosphatase IHC assay and were quantified on fresh-frozen tumor samples, using a modified dextran-coated charcoal (DCC) assay. RESULTS: 7 of 21 tumors had visually detectable nuclear ER by use of IHC staining, whereas 8 of 21 tumors were positive for ER by use of the DCC assay. The ER-positive cells in 5 IHC-positive tumors were epithelial cells with histologic criteria of early malignancy. The remaining 2 ER-positive tumors detected by use of IHC had ER-positive mast cells within areas of connective tissue around the tumor. CONCLUSIONS: Immunohistochemistry is an additional method for detection of ER in canine mammary tumors. The major advantage of this type of assay is that it may be performed on formalin-fixed tissues, and individual ER-positive cells may be identified. Discovery of ER-positive mast cells by use of IHC is of concern, particularly if the ER status of a tumor is based on DCC results alone. CLINICAL RELEVANCE: Because most canine mammary tumors are fixed in formalin prior to histologic evaluation, an IHC assay that identifies ER-positive cells is desirable. Adjunctive antiestrogen therapy could be administered to dogs with ER-positive tumors.

Animals↗

Non-tuberculous mycobacterial infection in children with cancer.

Reported here is the clinical presentation and management of patients with rapidly growing non-tuberculous mycobacterial infection diagnosed in a paediatric oncology unit. A retrospective analysis that correlated patient isolates with the children's cancer registry revealed two cases of non-tuberculous mycobacterial infection; both had been observed within the last 6 years and were due to Mycobacterium chelonae. The first case was line-associated and the second was a disseminated infection. In both cases the patients were lymphopenic and had had indwelling vascular catheters. Neither patient was neutropenic. The literature on mycobacterial infection in children with cancer is also reviewed.

Child, Preschool↗

Cerebral candidiasis in a child 1 year after leukaemia.

We describe an unusual case of a late presentation of a fungal brain abscess in a non-neutropenic child 1 year after completing chemotherapy for M5 acute myeloid leukaemia (AML). Biopsy of the mass identified candidal hyphae and the patient was treated with 5 mg/kg of liposomal amphotericin B for 6 weeks. The lesion resolved completely and the child remains well 2 years later. Invasive fungal infection should be included in the differential diagnosis of unexplained symptoms in patients who have previously received intensive chemotherapy.

Amphotericin B↗

Findings of the first comprehensive radiological monitoring program of the Republic of the Marshall Islands.

The Marshall Islands was the primary site of the United States atomic weapons testing program in the Pacific. From 1946 through 1958, 66 atomic weapons were detonated in the island country. For several decades, monitoring was conducted by the U.S. Department of Energy (or its predecessor agencies) on the test site atolls and neighboring atolls. However, 70% of the land area of the over 1,200 islands in the Marshall Islands was never systematically monitored prior to 1990. For the 5-y period from 1990 through 1994, the Government of the Republic of the Marshall Islands undertook an independent program to assess the radiological conditions throughout its 29 atolls. The scientific work was performed under the auspices of the Section 177 Agreement of the Compact of Free Association, U.S. public law 99-239, signed in 1986 by President Ronald Reagan. Although the total land area of the nations is a scant 180 km2, the islands are distributed over 6 x 10(5) km2 of ocean. Consequently, logistics and instrumentation were main considerations, in addition to cultural and language issues. The core of the monitoring program was in-situ gamma spectrometry measurements made on more than 400 islands. Native foods including coconuts and other tropical fruits were sampled as well as more than 200 soil profiles and more than 800 surface soil samples. The fruits, soil profiles and surface soil samples have been analyzed for all gamma emitters with an emphasis on determining concentrations of 137Cs; the surface soil samples were also analyzed for 239+240Pu. All measurements were conducted in a radiological laboratory built in the capital city of the Marshall Islands specifically for the purposes of this study. The program was extensively assisted in the field and in the laboratory by Marshallese workers. The interpretation of environmental radiation data in the Marshall Islands required thoughtful analysis because the atolls lie along a latitude and precipitation gradient that effected the deposition of local and global fallout. The objective of this paper is to report findings for all atolls of the Marshall Islands on the 137Cs areal inventory (Bq m(-2)) and the external effective dose-rate (mSv y(-1)), the projected internal effective dose-rate (mSv y(-1)) from an assumed diet model, and surface soil concentrations of 239,240Pu (Bq kg(-1)) for selected northern atolls. Interpretation is also provided on the degree of contamination above global fallout levels. This report provides the first comprehensive summary of the radiological conditions throughout the Marshall Islands.

Micronesia↗

Psychometric scores and persistence of irritable bowel after infectious diarrhoea.

BACKGROUND: Although previous studies have shown that psychological disturbances are frequently associated with the irritable bowel syndrome (IBS), the relation was not necessarily cause and effect. The development of chronic bowel symptoms resembling IBS after an episode of acute gastroenteritis has allowed us to examine prospectively the role of psychological factors. METHODS: 75 patients with acute gastroenteritis completed a series of psychometric tests soon after admission to hospital. Of these, 22 had persistent symptoms compatible with IBS after the acute illness, and in 20 of these the symptoms were still present at six months. FINDINGS: At the time of their initial illness, patients who subsequently developed IBS symptoms had higher scores for anxiety, depression, somatisation, and neurotic trait than those who returned to normal bowel function. The psychometric scores had not changed when remeasured three months after the acute illness. Lactose malabsorption was not an important factor. INTERPRETATION: These results support the hypothesis that psychological factors are important in IBS.

Acute Disease↗

Dose assessment activities in the Republic of the Marshall Islands.

Dose assessments, both retrospective and prospective, comprise one important function of a radiological study commissioned by the Republic of the Marshall Islands (RMI) government in late 1989. Estimating past or future exposure requires the synthesis of information from historical data, results from a recently completed field monitoring program, laboratory measurements, and some experimental studies. Most of the activities in the RMI to date have emphasized a pragmatic rather than theoretical approach. In particular, most of the recent effort has been expended on conducting an independent radiological monitoring program to determine the degree of deposition and the geographical extent of weapons test fallout over the nation. Contamination levels on 70% of the land mass of the Marshall Islands were unknown prior to 1994. The environmental radioactivity data play an integral role in both retrospective and prospective assessments. One recent use of dose assessment has been to interpret environmental measurements of radioactivity into annual doses that might be expected at every atoll. A second use for dose assessment has been to determine compliance with a dose action level for the rehabilitation of Rongelap Island. Careful examination of exposure pathways relevant to the island lifestyle has been necessary to accommodate these purposes. Examples of specific issues studied include defining traditional island diets as well as current day variations, sources of drinking water, uses of tropical plants including those consumed for food and for medicinal purposes, the nature and microvariability of plutonium particles in the soil and unusual pathways of exposure, e.g., that which might be associated with cooking and washing outdoors and inadvertent soil ingestion. A study on the prevalence of thyroid disease is also being conducted and the geographic pattern of disease may be useful as a bioindicator of the geographic pattern of exposure to radioiodine. Finally, an examination is underway of gummed film, fixed-instrument, and aerial survey data accumulated during the 1950's by the Health and Safety Laboratory of the U.S. AEC. This article gives an overview of these many different activities and a summary of recent dose assessments.

Diet↗

c-Fos expression in brain in response to hypotension and hypertension in conscious rats.

Hypotension- and hypertension-evoked expression of the protein product, Fos, of the immediate early gene c-fos was assessed throughout the rat brain as an approach for describing the neuronal populations that respond to alterations in arterial blood pressure. Conscious, chronically catheterized rats were treated with the vasoconstricting drug phenylephrine or the vasodilatating drug hydralazine to increase or decrease, respectively, arterial pressure by approx. 40 mm Hg for 90 min. Rats were then anesthetized, fixed by vascular perfusion, and sections representing the entire brain were processed for the immunocytochemical localization of Fos. In control rats treated with isotonic saline, few Fos-positive neurons were observed. In contrast, phenylephrine and hydralazine treatments resulted in different, yet reproducible, patterns of Fos expression in the brain, with hydralazine evoking Fos expression in more brain regions than phenylephrine. Brain regions containing Fos-positive neurons in rats treated with hydralazine included nucleus tractus solitarius, area postrema, caudal ventrolateral medulla, rostral ventrolateral medulla, bed nucleus of the stria terminalis, amygdala, paraventricular nucleus, supraoptic nucleus, subfornical organ and the Islands of Calleja. The nucleus tractus solitarius, paraventricular nucleus and the amygdala also contained Fos-positive neurons in phenylephrine-treated rats, although the number of Fos-positive neurons was always less than that noted in the hydralazine-treated rats and the location of Fos-positive neurons within these regions tended to differ between treatments. These results generally fit within an emerging understanding of brain circuitry underlying cardiovascular regulation.

Animals↗

Primary group A streptococcal peritonitis.

Primary peritonitis caused by Group A beta-haemolytic streptococci (GAS) is extremely rare and is usually only seen in the presence of underlying disease. This report describes the case of a previously fit young woman who developed primary GAS peritonitis. She had a laparotomy performed at which large amounts of intra-peritoneal pus was identified but no focus of infection was found. Broad spectrum antibiotics were initially used, these were changed to intravenous benzylpenicillin when GAS was isolated. She made a good recovery and was discharged 2 weeks after admission on oral amoxycillin. The organism was serotyped as T3/M3/R3 (opacity factor negative) and it is interesting that the same serotype was isolated from a throat swab taken from her daughter. We also discuss the possible routes of infection and the epidemiology of invasive GAS disease.

Acute Disease↗

Traumatic thoracic aortic rupture: investigation determines outcome.

Blunt thoracic aortic rupture (TAR) initially presents with subtle signs but is usually fatal if not diagnosed and treated early. Does the diagnostic process affect outcome? The definitive test most widely promoted is thoracic (arch) aortography but is usually only available in major teaching hospitals. Thoracic computerized tomography (CT) scanning is more readily available but its role in diagnosis of TAR is unproven. A retrospective review of trauma databases and medical record indexes over a 7 year period identified 38 patients presenting with TAR at Westmead and Royal North Shore Hospitals in the period 1984-91. Thirteen patients (34%) were dead on arrival or died within 15 min of arrival at either hospital. Five patients (13%) who arrived in cardiac arrest (with suspected TAR) died after immediate thoracotomy (two in the Emergency Department and three in the operating room). Two patients (5%) died from severe head injuries and were not investigated for TAR. Eighteen patients (47%) remained alive long enough for investigation and were considered potentially salvageable. Nine of these survived. Only 13 patients had arch aortography. No patient survived without an aortogram. Five patients had a chest CT scan; aortography followed in four patients. Computerized tomography scans delayed aortography or were misinterpreted. Review of all trauma thoracic (arch) aortograms for the same period at Westmead Hospital revealed a diagnosis of TAR in 7.4%. Blind thoracotomy did not result in survival. Computerized tomography scanning of the chest was of no value in the management of this injury. Early suspicion of possible thoracic aortic rupture demands urgent arch aortography and this remains the diagnostic 'gold standard'.

Adolescent↗

PNMT-containing neurons of the C1 cell group express c-fos in response to changes in baroreceptor input.

The immunocytochemical detection of Fos, the protein product of the immediate-early gene c-fos, was used as a marker for activated neurons to examine whether the C1 neurons in the rat rostral ventrolateral medulla (RVLM) respond to changes in baroreceptor afferent activity. After hydralazine-induced hypotension or sinoaortic denervation, two treatments that reduce baroreceptor afferent activity, numerous Fos-positive neurons were observed in the RVLM. The number of Fos-positive neurons in the RVLM was counted in brain stem sections from hydralazine-treated rats that had been previously injected with Fluorogold into the upper thoracic spinal cord to label spinally projecting RVLM neurons as well as stained for phenylethanolamine-N-methyltransferase (PNMT) as a marker of C1 neurons. The results indicate that approximately 80% of the C1 neurons expressed Fos in response to hydralazine injection; this was true of spinally projecting C1 neurons as well as those C1 neurons that were not labeled with Fluorogold. Furthermore, in hydralazine-treated rats, the majority of Fluorogold-labeled Fos-positive neurons contained PNMT. These results suggest that C1 neurons are sensitive to baroreceptor afferent input and support a role of these neurons in cardiovascular regulation.

Animals↗

The influence of graft type on patency of infrainguinal arterial bypass grafts.

Between 1985 and 1992, 328 patients underwent 392 infrainguinal reconstructions. Indications for operation were disabling claudication in 126 patients, critical limb ischemia in 246 and uncomplicated popliteal aneurysm in 20. Grafts were to the above knee popliteal artery in 134 patients, below knee popliteal artery in 176 and infrapopliteal ("distal") in 82 patients. Graft types included 160 reversed saphenous vein (RSV), 95 polytetrafluoroethylene (PTFE), 84 nonreversed saphenous vein (NRSV), 41 composite grafts (PTFE plus vein) and 12 others. Results show the five year patency rate for all grafts of 58 percent and limb salvage (for limb ischemia) of 74 percent. Above knee and below knee popliteal grafts (three year patency rates of 72 and 66 percent) performed significantly better than distal grafts (51 percent three year patency rate, p < 0.025). NRSV grafts comprised 63 ex situ ("translocated") and 21 in situ grafts. No significant difference was shown between these (two year patency rates of 62 and 65 percent). There was no significant difference between RSV and NRSV grafts in this series, although RSV tended to show higher patency rates. Composite grafts (below knee, three year patency rate of 45 percent) had significantly lower three year patency rates than below knee RSV (79 percent, p < 0.005). RSV remains the conduit of choice in this unit, with long term patency comparable with other published series. Use of NRSV (translocated and in situ) allows increased use of autogenous vein with the associated higher patency rates compared with prosthetic materials and is the graft of choice if the long saphenous vein is not suitable for use in the standard reversed method. The translocated technique allows more flexibility in the use of nonreversed vein with results comparable with the in situ technique. Composite grafts provide a useful alternative to PTFE alone for infrageniculate grafting when insufficient autogenenous vein is available.

Adult↗

Duplex ultrasound diagnosis of lower limb deep venous thrombosis.

To compare a non-invasive technique with contrast venography in the diagnosis of lower limb deep venous thrombosis (DVT), 355 patients (380 limbs) were examined over 15 months, using Duplex ultrasound. During this period, ascending venograms were performed in 53 of these patients (56 limbs) and the results were compared. Duplex detection of intraluminal thrombus was based on venous compressibility, Doppler-derived flow spectra, and visualization of thrombus within the lumen. Venography was designated the 'gold standard'. Duplex scanning had a sensitivity of 90.9%, and specificity of 91.3% in diagnosing DVT anywhere in the lower limb. Sensitivity, specificity, and accuracy were best in the femoral segment (95.2%, 100%, 98.2%, respectively), and fell slightly in the more distal limb: popliteal segment (90.4%, 97.1% and 94.6%), and calf veins (88.8%, 92.0% and 90.4%). These results indicate that duplex scanning produces sufficiently accurate data in the diagnosis of lower limb DVT to warrant its clinical use. It provides both the facility for diagnosis without the risks of contrast venography, and permits repeated imaging to follow the immediate progression of disease and efficacy of treatment.

Humans↗

Peritoneal morphology on maintenance dialysis.

Thirty-eight peritoneal biopsies from 37 patients with normal renal function or with end-stage renal failure without replacement therapy or utilizing continuous ambulatory peritoneal dialysis (CAPD), haemodialysis (HD) or a functioning transplant were examined histologically. No abnormality in peritoneal membrane morphology was observed in uraemia in the absence of dialysis. Significant abnormalities of peritoneal membrane morphology were observed in association with CAPD, the predominant finding being the development of peritoneal fibrosis which had a deleterious effect on membrane function. Abnormal peritoneal morphology was less commonly observed in patients on maintenance HD and with functioning transplants but may have implications regarding the future use of CAPD in these patients.

Adult↗