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Biomedical subjects

J Morgan

Publications and source records attributed to J Morgan.

At least 181 records · Page 10Linked to original sources
PubMed1992

Hepatic resections for primary and metastatic tumors using the ultrasonic surgical dissector.

We have previously described the development of new hepatic surgical techniques using the ultrasonic surgical dissector. With 10 years' experience, we have found that major liver resections have been simplified and that the technique is repeatable in hands other than our own. Thirty-three patients had 37 tumors, averaging 5.65 cm in size, resected with an average blood loss of only 1,020 mL per case, which included 5 right trisegmentectomies, 12 lobectomies, 15 segmental resections, and 4 subsegmental resections. Twenty-two patients had metastatic colorectal cancer. Blood transfusion requirements averaged only 2.24 units in long-term survivors, which was significantly less than the 3.5 units received by patients who have since died (p = 0.092). There were no operative deaths. The median survival of these 22 patients was 56 months, and the 5-year actuarial survival rate was 35%. All of the early deaths occurred in patients with more than four tumors, and no patient with less than four tumors died before 42 months with recurrent disease. Six patients had bilateral tumors, and the fact that patients survived into the fourth and fifth post-resectional year indicates that resection was worthwhile. All these patients had Dukes' C primary tumors, but we found no statistical difference in survival between patients with Dukes' B and Dukes' C lesions. The results indicate that hepatic resection with the ultrasonic surgical dissector decreases blood loss, requires few transfusions, is safe to perform, and is associated with excellent long-term survival.

Adolescent↗
PubMed1992

A study of coagulase-negative staphylococci with reference to slime production, adherence, antibiotic resistance patterns and clinical significance.

Two hundred and fifty-one strains of coagulase-negative staphylococci (CNS) isolated from patients in hospital and the community were investigated for slime production and adherence as indicators of pathogenicity. Staphylococcus epidermidis formed 68.5% (126) of the isolates of CNS from blood and central venous catheter (CVC) tips, of which 46.0% (58) were slime-positive and adherent. Clinically significant infections were associated with 55.2% (32) of the slime-positive adherent strains isolated and 11.1% (four) of slime-negative non-adherent strains of S. epidermidis. For other species of CNS isolated from blood and CVC tips 74.1% (43) were slime negative non-adherent and 18.6% (eight) of these were considered clinically significant isolates while none of the slime positive adherent strains were associated with a clinically significant infection. Slime production and adherence were not characteristic properties of CNS causing community-acquired urinary tract infection or colonizing the nasal mucosa. It is concluded that slime production and adherence had a limited role in the differentiation between clinically significant and contaminant strains isolated from blood cultures; however, the absence of slime and adherence in isolates of S. epidermidis suggested a lack of pathogenicity.

Bacterial Adhesion↗
PubMed1992

Use of photosensitive, antibody directed liposomes to destroy target populations of cells in bone marrow: a potential purging method for autologous bone marrow transplantation.

Liposomes containing the photosensitive dye sulphonated aluminium phthalocyanine (AlSPc) were coupled to polyclonal sheep anti-mouse-Ig antibody and bound to cells coated with specific mouse monoclonal antibody. When illuminated with red light, the AlSPc in the liposomes was activated to produce singlet oxygen and the antibody and liposome targeted cells were destroyed. DW-BCL cells (an Epstein Barr virus immortalised B-cell line) were targeted with an anti-B-cell antibody (8A) and killed specifically, both alone and in the presence of bone marrow mononuclear cells (BM-cells), without phototoxic effects on the untargeted bone marrow CFU-GM progenitor cells. The presence of an excess of non-target cells did not interfere with antibody and liposome binding, or light access to target cells. Similar results were obtained with T-lymphocytes as target cells using anti-CD3 antibody. Specific targeting to the B-cells was demonstrated in the cell mixtures by use of fluorescent microscopy combined with a sensitive technique to detect low levels of AlSPc fluorescence, a cooled charge couple device (CCD) camera. This was also able to show low levels of non-specific background binding of AlSPc to BM-cells and a small population of cells that took up AlSPc in the absence of antibody. The latter were shown to be monocytes by flow cytometry.

Bone Marrow↗
PubMed1992

The impact of a physically ill parent on adolescents: cross-sectional findings from a clinic population.

The degree to which the physical illness of a parent affects adolescents is unknown. This study examines this issue through a cross-sectional survey of patients referred consecutively to an adolescent outpatient psychiatry clinic. Demographic and clinical data concerning symptoms, diagnosis of major depression, peer isolation, and family functioning were collected on all subjects from both the adolescent and a parent (usually the mother). No significant differences were found between the groups on measures of family functioning, peer isolation and major depression. According to both youth and parent report, adolescents with physically ill parents had more somatic symptoms than controls. These findings are discussed in the light of the existing literature and the methodological shortcomings of the study.

Adolescent↗
PubMed1992

Adrenergic stimulation of bovine non-pigmented ciliary epithelial cells raises cAMP but has no effect on K+ or Cl- currents.

Freshly isolated bovine nonpigmented ciliary epithelial cells were studied using the whole-cell voltage-clamp and permeabilized patch techniques. In a study of 148 cells three classes of cell were found; those containing inward currents alone, 31%; those containing outward currents alone, 37% and those containing both inward and outward currents, 32%. The outward currents exhibited slow, delayed activation, were blocked by tetraethylammonium (TEA+) but were not effected by changes in [Cai] suggesting they are K(+)-currents similar to IK(V), the delayed rectifier. The inward currents were reduced by TEA+ and blocked by Cs+ suggesting they are inward rectifier K(+)-currents. Intracellular cAMP levels were increased by isoprenaline with a Ka of 20 nM. However, the resting membrane potential recorded from whole ciliary processes in intracellular microelectrode studies was not effected by adrenergic stimulation, neither were the leak current, the outward current nor the sustained inward current significantly effected by isoprenaline, noradrenaline or dibutyryl-cAMP in whole-cell and permeabilized patch clamp studies.

Adrenergic Agonists↗
PubMed1992

Signal enhancement in fluorescence microscopy and flow cytometry using fluorescent liposome-antibody conjugates as second layer reagents.

We have developed small unilamellar liposomes (SUV) containing carboxyfluorescein for indirect immunophenotyping of cells by fluorescent microscopy and flow cytometry. Covalently coupled to anti-mouse Ig and anti-human Ig with mouse monoclonal antibodies and human typing antisera respectively, these conjugates can increase sensitivity by a factor of 10 compared to fluorescein isothiocyanate (FITC) conjugates. No increase in background fluorescence was observed. The reagents have been used to detect a low density antigen, the interleukin-2 receptor, on resting T-cells and to overcome the quenching effect of haemoglobin in fluorescent phenotyping of red cells. This has allowed to accurately estimate blood grouping in mixed fields and with small numbers of cells. We have determined the blood group of fetal red cells obtained from a chorionic villous sample at 10 weeks gestation and predicted severe hemolytic disease. This was confirmed by fetal sampling at 19 weeks and several intra-uterine transfusions were undertaken before a successful delivery at 36 weeks. Applications of the method in leucocyte phenotyping and transfusion medicine are discussed.

Animals↗
PubMed1991

Complement activation during bypass in acquired C1 esterase inhibitor deficiency.

Serial complement estimations during cardiopulmonary bypass are reported in a patient with acquired C1 esterase inhibitor deficiency. Although the extent of classic and alternative pathway activation appeared appropriate, exaggerated common pathway activation with massive increase in the C3d:C3 ratio occurred. A fatal hemostatic disorder, pulmonary edema, and circulatory collapse ensued despite prophylaxis and therapy.

Aged↗
PubMed1991

Pulmonary function in relation to cigarette smoking and smoking cessation. MRFIT Research Group.

BACKGROUND: More than half of the subjects in the MRFIT smoked at baseline and 10% of the subjects stopped smoking permanently during the first year of the trial. In this report, rates of decline in forced expiratory volume in 1 sec (FEV1) are compared for early permanent quitters and smokers who continued to smoke throughout the trial. METHODS: Since pulmonary function testing was not standardized across all centers until the third annual visit cycle, change in FEV1 is examined over the latter half of the trial; the level of FEV1 is analyzed cross-sectionally at the midpoint of the trial. Analyses are limited to 4,926 subjects who never used beta-blockers or smoked cigars, cigarillos, or pipes during the trial and who had annual FEV1s measured over 2-4 years in the latter half of the trial. RESULTS: Quitters during the first 12 months experienced smaller declines in FEV1 over the latter half of the trial than continuing smokers, with -50.7 ml/year versus -59.0 ml/year, respectively, adjusted for the level of FEV1 (P = 0.05). Cross-sectionally, those who had never smoked, former smokers, quitters, and continuing smokers showed a gradient of decreasing FEV1, and all four smoking groups were significantly different from each other (P less than 0.05). CONCLUSIONS: These data suggest that if a middle-aged, healthy smoker stopped smoking permanently, he could expect his FEV1 to deteriorate at a more gradual rate 3-4 years after stopping smoking than a similar smoker who continued to smoke. No information was available for the complete MRFIT cohort on the pulmonary function effects immediately following smoking cessation.

Adult↗
PubMed1991

Liposomes in haematology.

Liposomes were first described nearly a quarter of a century ago and have been useful models for studying the physical chemistry of lipid bilayers and the biology of the cell membrane. It was also realised that they might be used as vehicles for the delivery of drugs but clinical applications have been slow to emerge. Proposed clinical uses have included vaccine adjuvancy, gene transfer and diagnostic imaging but the major effort has been in the development of liposomes as targetable drug carriers in the treatment of malignancy. Although based on good in vitro data and animal studies, the strategies have been mostly impractical due to the predominant but unwanted uptake by the reticuloendothelial system and the limited extent of extravasation. The same features have nonetheless been turned to advantage in the case of amphotericin B which has recently become the first liposomally formulated agent to be licensed for parenteral use. Liposomal doxorubicin is currently also being evaluated in clinical trials. The early evidence suggests that while liposomal encapsulation may not greatly enhance their efficacy the toxicity of these agents is greatly attenuated.

Drug Carriers↗
PubMed1991

The immune system in hereditary hemochromatosis: a quantitative and functional assessment of the cellular arm.

The objective of this investigation was to evaluate certain quantitative and functional characteristics of the effector cells of the cellular arm of the immune system in hereditary hemochromatosis (HH) with respect to treatment status. Two observations were consistent with the postulate that the elevated levels of storage iron has in vivo immunoregulatory properties: (1) the absolute number of CD8-positive T cells were significantly elevated in untreated HH patients (n = 7) and reduced in treated patients (n = 7), as compared with controls; and (2) the proliferative response of peripheral blood mononuclear cells from untreated HH patients to mitogens was suboptimal but the response of peripheral blood mononuclear cells (PBM) from treated HH patients was normal. Furthermore, immunoglobulin secretion by PBM from treated HH patients as compared to controls was altered. Finally, one T effector cell abnormality was unrelated to treatment status in that a subset of mature, non-activated T lymphocytes aberrantly formed thermostable erythrocyte-rosettes (TE-R), a lymphoid surface marker usually expressed on thymocytes or activated T cells. Taken together these data define certain immune alterations that are consistent with the interpretation that cellular immunity may be influenced by the high level of storage iron in HH patients.

Antibody Formation↗
PubMed1990

Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice.

The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02).

Administration, Oral↗
PubMed1990

The diagnosis and prognosis of autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on the short arm of chromosome 16, but in about 4 percent of families with the disorder it is caused by unknown mutations elsewhere in the genome. The natural course of the disease in both genetic forms is not well characterized. METHODS: We studied 17 families with autosomal dominant polycystic kidney disease to compare presymptomatic diagnosis by ultrasonography with diagnosis by genetic-linkage studies and to relate clinical variation of the disease to whether the PKD1 mutation was implicated. RESULTS: In 10 families the disorder was found to cosegregate with polymorphic DNA markers flanking the PKD1 locus, in 2 families it did not, and in 5 families linkage could not be determined. In the 10 families with the PKD1 mutation, 46 percent of the members less than 30 years old who had a 50 percent risk of inheriting a mutation had renal cysts, as compared with 11 percent of the members of the two families without linkage (P less than 0.001). In the PKD1 families, all 67 diagnoses made by ultrasonography were confirmed by determination of the genotype as inferred from linkage. Forty of 48 members (83 percent) less than 30 years old who inherited the PKD1 mutation had renal cysts. All 27 members 30 years old or older who inherited the mutation had renal cysts, suggesting that the probability of a false negative diagnosis did not exceed 0.13 in this age group (P less than 0.05). The mean (+/- SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 +/- 1.9 years, as compared with 69.4 +/- 1.7 years among members with cysts in the families without linkage (P = 0.0025). Hypertension and renal impairment were less frequent and occurred later in the families without the PKD1 mutation. CONCLUSIONS: At present, in most persons with a 50 percent risk of autosomal dominant polycystic kidney disease, imaging techniques are the only mode of reaching a diagnosis before symptoms appear. In such persons a negative ultrasonographic study during early adult life indicates that the likelihood of inheriting a PKD1 mutation is small. In the few who inherit a non-PKD1 mutation for polycystic kidney disease, renal failure is likely to occur relatively late in life.

Adult↗