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Biomedical subjects

A Malcolm

Publications and source records attributed to A Malcolm.

At least 19 recordsLinked to original sources
PubMed1999

Videoendoscopic diagnosis of esophageal motility disorders.

BACKGROUND: Esophageal motility disorders are usually diagnosed by manometry. We evaluated videoendoscopy as a diagnostic test. METHODS: In this study, 20 patients with achalasia, 13 with scleroderma, and 33 control subjects had a standard endoscopic examination followed by protocol videotaping of swallows to observe contractions in the esophagus and in the lower esophageal sphincter. Tapes were later reviewed by 2 blinded observers who recorded their motility findings and diagnoses. RESULTS: In the mid esophagus at 25 cm, lumen-occluding peristaltic contractions were identified in 26 of 33 control subjects versus 1 of 20 achalasia (p < 0.001) and 3 of 13 scleroderma patients (p < 0.005). As viewed in the lower esophagus, the lower esophageal sphincter opened normally in 31 of 33 control subjects versus 1 of 20 achalasia (p < 0.001). In scleroderma, the sphincter never closed in 12 of 13 patients (p < 0. 001 versus control subjects). A diagnostic sequence of sphincter opening followed by contraction in the esophageal body and subsequent sphincter closing was seen in 33 of 33 control subjects, 2 of 20 achalasia, and 1 of 13 scleroderma patients (both, p < 0. 001). The observers made the correct diagnosis in 96% of cases. CONCLUSIONS: Achalasia and esophageal scleroderma can be identified by endoscopic observation of motility. This procedure may represent an adjunctive diagnostic test to manometry.

Endoscopy, Digestive System↗
PubMed1999

IgY antiporcine endothelial cell antibodies effectively block human antiporcine xenoantibody binding.

Avian IgY antibodies are structurally different from mammalian IgGs and do not fix mammalian complement components or bind human Fc receptors. As these antibody-mediated interactions are believed to play significant roles in both hyperacute rejection (HAR) and acute vascular xenograft rejection (AVXR), IgY antibodies to xenoantigen target epitopes may inhibit these rejection processes. In this report, we show that chicken IgY antibodies to alpha-Gal antigen epitopes and to other porcine aortic endothelial cell (PAEC) antigens block human xenoreactive natural antibody binding to both porcine and rat cardiac tissues and porcine kidney tissues. Chicken IgY antibodies blocked complement-mediated lysis of PAECs by human serum, and inhibited antibody-dependent cell-mediated lysis of PAECs by heat-inactivated human serum plus peripheral blood leukocytes. Binding of IgY to porcine endothelial cells did not affect cell morphology nor expression of E-selectin. These results suggest that avian IgYs could be of potential use in inhibiting pig-to-human xenograft rejection.

Animals↗
PubMed1998

Holmium laser resection of the prostate versus neodymium:yttrium-aluminum-garnet visual laser ablation of the prostate: a randomized prospective comparison of two techniques for laser prostatectomy.

OBJECTIVES: To directly compare holmium laser resection of the prostate (HoLRP) with neodymium:yttrium-aluminum-garnet visual laser ablation of the prostate (VLAP), which represent two fundamentally different methods of laser prostatectomy. METHODS: In a randomized, prospective comparison, a total of 44 men with symptomatic benign prostatic hyperplasia (BPH) were treated with either HoLRP or VLAP. Standard preoperative assessment included American Urological Association (AUA) symptom score, peak urinary flow rates (Qmax), ultrasound prostate volume, and residual urine measurements. Pressure-flow urodynamics were performed preoperatively and at 3 months postoperatively. Intraoperative and perioperative factors were assessed. The patients were followed at 1, 3, 6, and 12 months following the procedure. RESULTS: There were no significant differences between the patient groups for any preoperative parameter. The mean total operating time was longer in the HoLRP group (52 minutes) compared with the VLAP group (41 minutes) (P <0.01). The mean catheter times were 1.4 days (HoLRP) and 11.6 days (VLAP) (P <0.001). These times included the 9% of patients undergoing HoLRP and 36% of patients undergoing VLAP who required recatheterization. Immediate postoperative dysuria scores were higher in the VLAP group compared with the HoLRP group. There were no significant differences in AUA scores between the two treatment groups at any postoperative interval. The Qmax values were greater at follow-up in the HoLRP group, but statistical significance was not achieved at 12 months. However, both PdetQmax and Schäfer grade measurements taken at 3 months postoperatively were significantly lower in the patients undergoing HoLRP. Three patients (14%) required reoperation in the VLAP treatment arm but no patient who underwent HoLRP has required reoperation to date. CONCLUSIONS: HoLRP results in significantly improved patient outcomes compared to VLAP.

Adult↗
PubMed1998

Ifosfamide-containing chemotherapy in Ewing's sarcoma: The Second United Kingdom Children's Cancer Study Group and the Medical Research Council Ewing's Tumor Study.

PURPOSE: To investigate the possibility that the substitution of ifosfamide for cyclophosphamide therapy for Ewing's sarcoma will improve survival over that seen in the first United Kingdom Children's Cancer Study Group (UKCCSG) Ewing's tumor study (ET-1). PATIENTS AND METHODS: Between 1987 and 1993,243 patients (138 men or boys) were entered onto the study. The median age was 13.5 years (range, 1.5 to 27 years). The median follow-up was 58 months. Chemotherapy included four courses of vincristine 2 mg/m2; ifosfamide 9 g/m2; and doxorubicin 60 mg/m2 administered every 3 weeks. Treatment of the primary tumor was with surgery and/or radiotherapy followed by ifosfamide 6 g/m2; doxorubicin 60 mg/m2; and vincristine 2 mg/m2; with actinomycin D 1.5 mg/m2 substituted for doxorubicin after a total dose of 420 mg/m2. RESULTS: Two hundred one patients had no metastases. One hundred eighteen patients had tumors of the axial skeleton and 125 patients had limb primary tumors. The major toxicities were hematologic and infective, but there were no toxic deaths. The overall survival rate was 62% (95% confidence interval [CI], 56 to 69) and relapse-free survival (RFS) 56% (95% CI, 49 to 62). For those with no metastases at diagnosis, the RFS rate was 62% and for those with metastases, 23%. Multivariate analysis showed age and site to have a significant effect on RFS. Pelvic sites had the worst RFS rate of 41%; other axial sites, 55%; and extremity tumors, 73%. Age younger than 10 years had an RFS rate of 86% versus 55% for older patients. The local relapse rate for axial tumors was 20% and for limb primary tumors was 2.4%. CONCLUSION: The 5-year survival rate of 62% is improved compared with the 44% survival rate achieved in ET-1. This is probably caused by the use of higher doses of ifosfamide compared with relatively low doses of cyclophosphamide in ET-1.

Adolescent↗
PubMed1997

Rumination syndrome.

Rumination is a syndrome characterized by repetitive regurgitation of small amounts of food from the stomach. The food is then partially or completely rechewed, reswallowed, or expelled. This syndrome is relatively common in infants and mentally challenged persons, but it also occurs in adults with normal intelligence. The rumination syndrome is an underappreciated condition in adults who frequently receive a misdiagnosis of vomiting due to gastroparesis or gastroesophageal reflux. Difficulties in establishing the correct diagnosis may be caused by a lack of awareness of the condition among physicians. This syndrome must be considered in the differential diagnosis of a patient with regurgitation, vomiting (especially postprandial), and weight loss. Reassurance, explanations, and behavioral therapy are currently the mainstays of treatment in adults with normal intelligence who have the rumination syndrome. Appropriately controlled trials are needed to establish the best therapy.

Adolescent↗
PubMed1997

Bone resorption and serum levels of vitamin D metabolites in the hypophosphataemic rat.

The supplementation of a low phosphate diet with vitamin D has been shown to result in an increase in bone resorption in the hypophosphataemic rat. The aim of the present study was to determine if administration of vitamin D to rats fed a vitamin D- and phosphate-depleted diet would result in an increase in the circulatory levels of the active vitamin D metabolite 1,25(OH)2D3 and an associated increase in bone resorption. Three groups of weanling Sprague-Dawley rats were used. The first group consisted of control animals on a normal laboratory stock diet and the second and third groups were experimental animals receiving a vitamin D- and phosphate-deficient diet with the third group receiving vitamin D supplementation. All animals were housed in the dark. After 30 days on the diet the experimental animals received 0.1 mmol NaH2PO4 by intraperitoneal injection. Blood was sampled at zero, 3, 6, 18 and 48 h post-injection and analysed for the vitamin D metabolites 25(OH)D3 and 1,25(OH)2D3, calcium and inorganic phosphate (Pi). The serum analyses revealed that the level of 25(OH)D3 in the hypophosphataemic animals was significantly lower than that of the control animals. However, the 1,25(OH)3D3 level was initially significantly higher, then dropped to the control level at 18 h post-intraperitoneal injection of phosphate. Further, the serum levels of 25(OH)D3 and 1,25(OH)2D3, calcium and Pi in the hypophosphataemic animals supplemented with vitamin D were significantly higher than those of the vitamin D-deficient animals. Also the vitamin D-supplemented animals exhibited significantly greater levels of bone resorption. These results therefore, are consistent with a role of 1,25(OH)2D3 in bone resorption in hypophosphataemic rats.

Analysis of Variance↗
PubMed1997

Superficial spreading melanoma and blue naevus within naevus spilus--ultrastructural assessment of giant pigment granules.

BACKGROUND: Abnormal melanosomes occur in naevus spilus (NS). OBJECTIVE: To determine whether melanoma arising in NS contains abnormal melanosomes. METHODS: Light and electron microscopy of melanoma within NS and congenital naevus (Case 1), and of blue naevus within NS (Case 2). Light microscopy of additional naevi and melanomas. RESULTS: The melanoma and NS (Case 1) both had large numbers of giant pigment granules (GPGs), demonstrated ultrastructurally to be melanosome macrocomplexes. These were not observed in a congenital naevus (Case 1), or in the blue naevus within NS (Case 2). Small numbers of GPGs were observed in 0/2 NS, 8/16 benign naevi and 11/16 malignant melanomas (MMs). CONCLUSION: NS may be associated with other melanocytic tumours including MM and blue naevi; abnormal melanosomes in NS may also be present in the associated tumour. The prognostic importance of these is unknown, but occasional GPGs in melanocytic lesions are a frequent finding.

Adult↗
PubMed1997

Pharmacological modulation of rectal tone alters perception of distention in humans.

OBJECTIVE: Drugs can alter perception of balloon distention of the GI tract. It has been proposed that the mechanism by which this occurs is through effects on visceral afferent pathways. Our hypothesis was that modulation of rectal tone will also influence the perception of rectal balloon distention. METHODS: Fasting and postprandial rectal tone, compliance, and perception of rectal distention were measured in 25 healthy subjects, using a five-armed, parallel, single-blinded study design. Each subject received either glucagon, nitroglycerin, clonidine, yohimbine, or saline. RESULTS: Rectal tone, but not compliance, influenced perception as measured by balloon distention of the rectum (r = 0.6, p = 0.002). Glucagon, nitroglycerin, and clonidine reduced and yohimbine increased fasting tone compared with saline. Compliance and postprandial tone were similar in all groups. Yohimbine increased rectal perception of distention. CONCLUSIONS: Tone is one of the factors that influences the sensory perception of balloon distention in the human rectum. Alpha2-adrenergic agents, a nitric oxide donor, and glucagon altered fasting rectal tone, but postprandial tone was similar after administration of each agent.

Adult↗
PubMed1996

Degenerative joint disease in the guinea pig. Use of magnetic resonance imaging to monitor progression of bone pathology.

OBJECTIVE: The suitability of magnetic resonance imaging (MRI) for serial monitoring of bone pathology in the guinea pig stifle joint, an in vivo model of osteoarthritis, was investigated. METHODS: MR images were compared with histologic features and radiographs of 1-mm-thick sections to determine the MR correlates of the bone changes. Ten guinea pigs were then imaged on 7 occasions over the first year of life, enabling serial measurements of subchondral bone thickness, subchondral pseudocysts, and osteophytes. RESULTS: The signal intensity of trabecular bone in MR images accurately reflected the degree of osteopenia and trabecular thinning noted around the cruciate ligament insertions. The extent of subchondral sclerosis and the development of marginal osteophytes were also accurately represented. Serial observations revealed that MRI can detect highly significant progression of lytic bone lesions, subchondral sclerosis, and osteophyte size over periods of 6 weeks. CONCLUSION: MRI is not only a reliable technique for the assessment of bone pathology but is also a useful tool for monitoring the progression of bone damage in osteoarthritis.

Animals↗
PubMed1996

Minocycline-induced liver injury.

Tetracycline may cause fatty infiltration of the liver; more recently, it has been reported to cause intrahepatic cholestasis with bile duct depletion. However, minocycline, a derivative of tetracycline, is not generally recognized to be hepatotoxic. We report a series of six cases of presumed minocycline-induced liver injury; five of these patients had acute hepatitic illness, whereas one had a more prolonged course with histological evidence of chronic hepatitis. In addition, three patients demonstrated abnormal anti-nuclear antibody levels, and one had positive double-stranded DNA.

Acne Vulgaris↗
PubMed1994

Identification of hybridomas derived from mouse CD5+ B lymphocytes by fluorescent staining for cytoplasmic CD5 expression.

The production of hybridomas derived from CD5+ B lymphocytes is important for studying the immunoglobulin gene repertoire and antibody specificity of this B-lymphocyte subpopulation. However, hybridomas derived from these lymphocytes invariably lose surface membrane expression of CD5 following hybridization. This impedes the unequivocal assignment of the generated hybridomas to the CD5+ B-lymphocyte subpopulation from unsorted, or partially sorted, cells. Recent studies have shown that mRNA transcripts of the CD5 gene and the protein product can be detected in the cytoplasm of some mouse hybridomas, indicating that although surface expression has been lost, they may have been generated from CD5+ B lymphocytes. These studies, however, have been unable to discount completely the possibility that aberrant cytoplasmic expression of the CD5 gene occurred as a direct consequence of the hybridization process. To confirm that cytoplasmic CD5 expression in the hybridomas is in fact directly related to the B-lymphocyte origin we have generated hybridomas from FACS-sorted CD5+ and CD5- murine splenic B lymphocytes, and determined their surface and cytoplasmic CD5 expression by fluorescence-activated cell sorting. Our findings reveal that all hybridomas derived from CD5+ B lymphocytes (nine hybridomas) were negative for surface but positive for cytoplasmic CD5 expression, whereas all hybridomas derived from CD5- B lymphocytes (nine hybridomas) were negative for both surface and cytoplasmic CD5 expression. This finding shows that staining for cytoplasmic CD5 expression provides an accurate method of determining the cellular origin of murine B-lymphocyte hybridomas.

Animals↗
PubMed1993

Retinoic acid receptor expression during the in vitro differentiation of human neuroblastoma.

Neuroblastoma cells differentiate in response to retinoic acid and cyclic AMP. We have examined the expression of retinoic acid receptors (RARs) in relation to neuroblastoma differentiation and show that short term exposure of SK N SH, SH SY 5Y AND GI LI N cells to physiological concentrations of retinoic acid results in induction of RAR-beta, particularly the lower transcript. Cyclic AMP has no effect on retinoic acid mediated induction and does not alter RAR expression patterns. These data are discussed in the light of evidence that retinoic acid and cyclic AMP act either on different control pathways or at different points within a common pathway.

Blotting, Northern↗
PubMed1992

Immunoglobulin heavy chain variable region gene utilization by B cell hybridomas derived from rheumatoid synovial tissue.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects synovial joints. Activated B lymphocytes and plasma cells are present in the synovial tissue and are thought to contribute to the immunopathology of the rheumatoid joint. To investigate rheumatoid synovial B lymphocytes, we have generated B cell hybridomas from synovial tissue of an RA patient. Here we describe the immunoglobulin VH gene repertoire of eight IgM- and 10 IgG-secreting synovial-derived hybridomas. The VH4 gene family is highly represented (38.5%) in this panel of hybridomas compared with the frequency of VH4 gene expression in circulating B lymphocytes reported previously (19-22%) and with the VH4 gene frequency we observed in a panel of hybridomas derived in the same manner from the spleen and tonsil of normal individuals (19%). The increased frequency of VH4 gene expression was not due to the expansion of a single B cell clone in vivo as none of these hybridomas was clonally related. Two synovial-derived hybridomas secreted autoantibodies; one (VH3+) secreted an IgM-rheumatoid factor (RF) and the other (VH4+) secreted IgM with polyreactive binding to cytoskeletal proteins and cardiolipin. The antibodies secreted by the remaining synovial-derived hybridomas were not reactive with the autoantigens tested. The VH gene usage in a proportion (5/17) of synovial-derived hybridomas that expressed CD5 antigen provided preliminary evidence that CD5+ B cells in RA synovium have a similar increase of VH4 gene expression reported for CD5+ B cells from normal individuals and patients with chronic lymphocytic leukaemia.

Adult↗
PubMed1991

Neoadjuvant cisplatin plus vinblastine chemotherapy in locally advanced non-small cell lung cancer.

Twenty-eight patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) received neoadjuvant chemotherapy with cisplatin (120 mg/m2 on days 1 and 29) and vinblastine (4 mg/m2 weekly for 6 weeks). At the completion of induction chemotherapy, all patients were assessed for resectability. Those patients judged to be resectable underwent thoracotomy. All remaining patients received thoracic radiation therapy (5500 cGy) followed by additional chemotherapy in those patients responding to neoadjuvant treatment. There were 15 partial responses to neoadjuvant chemotherapy for an overall response rate of 54% (95% confidence interval, 36% to 71%). Only five partially responding patients (18%) were thought to have had sufficient tumor regression to allow for a potentially curative resection. However, a complete resection was done in only two patients. Overall median survival was 12 months (range, 4 to 72 months) with 1-year, 2-year, and 3-year survival rates of 54%, 39%, and 11%, respectively. The primary toxicity associated with neoadjuvant chemotherapy was moderate to severe (Eastern Cooperative Oncology Group Grade 3 or 4) nausea and emesis in 25% of patients. Hematologic toxicity was relatively modest; only one patient had Grade 4 leukopenia (less than 1000/microliter). Fever and neutropenia were uncommon, and there were no documented septic episodes or treatment-related deaths. Compared with historic controls treated with radiation therapy alone, cisplatin-based neoadjuvant chemotherapy appeared to improve the median and long-term survival of Stage III NSCLC patients modestly.

Adenocarcinoma↗
PubMed1990

Chronic pericardial disease in patients with rheumatoid arthritis: a longitudinal study.

We have reviewed the clinical and investigative findings in 13 patients with chronic pericardial disease and seropositive rheumatoid arthritis. In eleven cases the diagnosis was made on clinical grounds, while the diagnosis was confirmed only at post-mortem in two patients. Pleural effusions were present in seven patients, while pulsus paradoxus was found in only one case. Echocardiograms were undertaken in ten patients and all showed evidence of pericardial effusions, which were usually small and sited posteriorly. A delayed ventricular filling pattern indicating abnormal ventricular relaxation was seen in two patients with cardiac tamponade. The surviving 11 patients were reviewed a median of three years after diagnosis of their pericardial disease. Pericardectomy had been performed in six, all of whom were asymptomatic and had a normal chest radiograph. Steroids alone had been given to the other five, and three of these remained dyspnoeic with cardiomegaly. The clinical features distinguishing chronic pericardial disease from other causes of right heart failure in rheumatoid arthritis patients are subtle. As management is fundamentally different, serious consideration should be given to the diagnosis of chronic pericardial disease in any patient with rheumatoid arthritis who presents with right-sided heart failure.

Adult↗