Search PubMed⌕ Search

Biomedical subjects

P Wilson

Publications and source records attributed to P Wilson.

At least 163 records · Page 9Linked to original sources
PubMed1996

Cytomegalovirus retinitis in AIDS patients: influence of cytomegaloviral load on response to ganciclovir, time to recurrence and survival.

OBJECTIVES: Despite life-long maintenance therapy, cytomegalovirus (CMV) retinitis frequently progresses in patients with AIDS. Virological markers that could clarify pathogenesis and identify risk factors for progression are required. DESIGN AND METHODS: We prospectively recruited 45 patients with CMV retinitis. Blood and urine samples were collected before and after induction therapy, and on a monthly basis thereafter during routine medical and ophthalmological assessment, and at any time retinitis progressed. CMV load was measured by quantitative-competitive polymerase chain reaction (PCR). RESULTS: The median time to first progression of retinitis was 78 days and to death was 8.7 months. Eighty-five per cent of patients who were PCR-positive at diagnosis of retinitis became PCR-negative after 21 days of ganciclovir induction therapy. Six patients who remained PCR-positive after 21 days of treatment had a significantly higher CMV load at presentation (P = 0.005), and a shorter time to first progression of retinitis of 40 days. High CMV loads in blood at presentation were associated with a shorter time to progression (P = 0.16; relative hazard, 1.57) and a significantly shorter time to death (P = 0.004; relative hazard, 1.76). This significant relationship with survival remained after adjustment for potential confounding variables (CD4 count, age, method of drug administration). CONCLUSIONS: We conclude that CMV load in the blood of AIDS patients is an important factor in the pathogenesis of retinitis, and quantification of CMV could be used to both select patients for controlled clinical trials and to optimize individual anti-CMV induction therapy.

AIDS-Related Opportunistic Infections↗
PubMed1996

Proliferative T cell responses to human papillomavirus type 16 L1 peptides in patients with cervical dysplasia.

Human papillomavirus type 16 (HPV-16) can cause genital warts, cervical dysplasias and carcinoma of the cervix. Cell-mediated immunity is thought to be important in protection against the virus and in its elimination, but little is known about the mechanisms involved. In a cross-sectional study we have demonstrated proliferative T cell responses to peptides representing the HPV-16 L1 capsid protein (aa 199-409) in the peripheral blood of 63% of patients (n = 41) with histological evidence of cervical dysplasia and in 45% of healthy age-matched controls (n = 11). This was achieved by generating short-term T cell lines (STLs) from each individual in vitro against a beta-galactosidase-HPV- 16 L1 (aa 199-409) fusion protein for 2 weeks, and then identifying the HPV epitopes they recognized with overlapping synthetic peptides (15-mers) spanning this region in 3 day specificity assays. Histological grading and HPV typing by PCR were performed on patients' cervical biopsies taken at the same clinical visit as the peripheral blood samples. An immunogenic region was identified between aa 311-345 in 73% of patients (18% in controls) who responded to HPV-16 L1 (aa 199-409). The number of responders to this region was significantly higher in patients with HPV-16-positive biopsies when compared to those with HPV-16-negative biopsies (P = 0.006), as was the number of responders to individual peptides 311-325 (NLASSNYFPTPSGSM; p = 0.04) and 321-335 (PSGSMVTSDAQIFNK; P = 0.004) representing this region. The mean level of response to each individual peptide was also higher in the patient group than the controls (P < 0.05). The most significant finding was that all patients with evidence of a current HPV-16 infection responded to one or more L1 peptides (P = 0.0004) and 92% had high grade cervical intraepithelial neoplasia (CIN III). We also found that the CIN III group was more likely to respond to any L1 peptide than either the atypical group (P = 0.04) or the controls (P = 0.05). Data from four individuals showed that the majority of peptide-specific STLs were CD4+ but some CD8+ STLs were also detected.

Amino Acid Sequence↗
PubMed1996

Proliferative T cell responses to the human papillomavirus type 16 E7 protein in women with cervical dysplasia and cervical carcinoma and in healthy individuals.

The levels of proliferative T cell responses to peptides representing the human papillomavirus type 16 (HPV-16) E7 protein have been measured using short-term T cell lines derived from peripheral blood of healthy women and those with cervical dysplasias and carcinoma of the cervix. In healthy individuals 47 percent (7/15) responded predominantly to the N- and C-terminal regions of the protein and 6/7 responders were to a single peptide between amino acids 80-94. In comparison 29 percent (9/31) of women with cervical dysplasia responded to HPV-16 E7, with a significantly reduced response to both the N- and C-terminal regions (P = 0.03 and 0.038, respectively). A higher proportion of responders was found in patients with high grade lesions (56 percent, 5/9) versus those with atypical or low grade histology (20 percent, 4/20) and the response to a single peptide between amino acids 75-94 was also increased in this patient group (P = 0.044). This may be a reflection of higher levels of current or previous exposure to HPV-16 in patients with high grade lesions. Correlation of T cell responses with HPV DNA type (detected by PCR of cervical biopsy tissue) showed that 3/9 (33 percent) HPV-16 DNA-positive individuals responded. This suggests that E7 may not be the dominant target of the immune response or that the response to E7 is down-regulated in these patients. In addition 4/18 (22 percent) HPV-16 DNA-negative individuals responded, suggesting that their T cells may have been primed by previous exposure to HPV-16 or that a cross-reactive response was detected. Proliferative T cell responses to both HPV-16 E7 and L1 were reduced in women with cervical carcinoma in comparison to those with cervical dysplasia and healthy controls. The observed down-regulation of responses to HPV-16 E7 in women with cervical dysplasia and cervical carcinoma may reflect an altered functional balance between subsets of T helper cells in HPV-16 infections.

Adult↗
PubMed1996

Intraaxonal injection of neurobiotin reveals the long-ranging projections of A beta-hair follicle afferent fibers to the cat dorsal horn.

1. The morphology and somatotopic organization of the spinal arborizations of identified A beta-hair follicle afferent fibers (HFAs) with receptive fields (RFs) on the digits have been investigated in the cat by the use of intraaxonal injection of the tracer n-(2 aminoethyl) biotinamide. 2. In three cats, the long-ranging projections of six HFAs were examined by selectively injecting afferents with RFs on digit 2, 4, or 5, directly over the digit 3 representation, and examining their collateral morphology in transverse sections of the spinal cord. The rostral and caudal boundaries of the digit 3 representation were determined by mapping the RFs of identified spinocervical tract (SCT) neurons. 3. In two more cats, three HFAs were injected at random rostrocaudal positions and their morphology was examined in parasagittal sections. In one animal (2 HFAs), the somatotopy of the digit representation was again determined by mapping the RFs of SCT neurons. In the remaining cat (1 HFA), the somatotopy of the dorsal horn was mapped from the RFs of unidentified dorsal horn neurons. 4. Hair follicle afferents emitted many more collaterals, over much greater rostrocaudal distances, than indicated by previous horseradish peroxidase studies, and all collaterals gave rise to synaptic boutons. 5. HFAs that have RFs confined to a small part of a digit give rise to bouton-bearing axonal branches throughout the entire rostrocaudal extent of the hindpaw representation.

Afferent Pathways↗
PubMed1996

Validation of a short food frequency questionnaire for assessment of dietary calcium intake in women.

OBJECTIVE: To assess the ability of a short food frequency questionnaire to measure dietary calcium intake in women. DESIGN: Estimates of calcium intake from the food frequency questionnaire were compared with those from seven-day estimated records in 58 Caucasian women aged 25-49 years in Dunedin, New Zealand. SUBJECTS: Subjects were recruited through poster and newspaper advertising around the central business district of Dunedin, New Zealand. Of 69 subjects initially recruited, nine failed to complete diet records and two were excluded on the basis that their diet record was unlikely to represent habitual intake. RESULTS: Mean dietary calcium intakes were 808.1mg/day from the estimated record and 776.9mg/day from the questionnaire. The mean difference in intake by the two methods (31.1mg, SD = 234.0, 95% CI = -30.4-92.7, p = 0.3) did not differ significantly from zero. The questionnaire classified women consuming less than 800mg calcium per day with 78% specificity. 81% of subjects when classified by the records fell into the same or adjacent quartiles when classified by the questionnaire. Only two subjects were grossly misclassified. CONCLUSIONS: The short food frequency questionnaire could be used to assess mean dietary calcium intake in young to middle aged women. The specificity of the questionnaire is high in identifying women who consume < 800mg calcium/day, therefore it could be used to target interventions for those with intakes below this level.

Adult↗
PubMed1996

Role of lactosylceramide and MAP kinase in the proliferation of proximal tubular cells in human polycystic kidney disease.

Polycystic kidney disease (PKD) is a common genetic disease characterized by the proliferation of epithelial cells, formation of cysts, and the progression of renal deficiency. We have investigated a possible role of glycosphingolipids in the proliferation of human kidney cells in this disease. The levels of glucosylceramide and lactosylceramide and the activity of glucosylceramide synthase (GlcT-1) and lactosylceramide synthase (GalT-2) were elevated 2-fold and 3-fold, respectively, in the PKD tissue compared to control. Lactosylceramide, but not glucosylceramide (10 microM) derived from PKD exerted a 4-fold stimulation in the proliferation of these cells. However, at a concentration of 40 microM, lactosylceramide and glucosylceramide both stimulated cell proliferation on the order of 10-fold and 2.5-fold, respectively, as compared to control. This phenomenon may be due to the enrichment of lactosylceramide containing shorter chain fatty acids (C16:0-C18:0). Lactosylceramide, but not glucosylceramide exerted a time-dependent stimulation in the phosphorylation of mitogen-activated protein kinase (p44 MAPK) in normal human kidney proximal tubular cells. Moreover, the kidneys and cultured cells from the PKD patients contained higher levels of the p44 MAPK as compared to normal human kidneys. In sum, our studies indicate that lactosylceramide present in the PKD kidney may stimulate cell proliferation via activation of the p44 MAPK, and contribute to the pathophysiology in this disease.

Adult↗
PubMed1996

Shoulder pain in the work place.

The incidence of shoulder injuries in the work place has risen significantly over the last 10 years. The purpose of this article is to review the anatomy and examination of the shoulder and to present an approach to treating shoulder disorders commonly seen in the injured worker.

Humans↗
PubMed1995

Doctors' legal position in treating temporarily incompetent patients.

Doctors in accident and emergency departments are sometimes presented with patients with potentially life threatening conditions who refuse to consent to treatment. The doctors then face a dilemma: to withhold necessary treatment or to act against a patient's express wishes. Two such cases are presented, and we asked a lawyer, two medical ethicists, a psychiatrist, and an accident and emergency physician to comment on the implications.

Adult↗
PubMed1995

Phase I clinical and pharmacokinetic study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762).

Methoxymorpholinyldoxorubicin (FCE 23762) is a novel, highly lipophilic doxorubicin analogue. It possesses potent in vitro and in vivo antitumor activity including efficacy in multidrug-resistant tumor cell lines. It is also metabolically activated in vivo resulting in an 80-fold increase in potency over the parent drug. In this phase I study the drug was administered by i.v. bolus injection at 3-week intervals. Fifty-three patients with refractory solid tumors were treated; 133 courses of FCE 23762 were administered at doses ranging from 30 to 2250 micrograms/m2. The dose limiting toxicity was reversible myelo-suppression (granulocytopenia and thrombocytopenia), demonstrating a delayed nadir and recovery in comparison to doxorubicin. Other toxicities included transient elevation of hepatic transaminases, delayed and prolonged nausea and vomiting, mucositis, anorexia, fatigue, and diarrhea. Heavily pretreated patients demonstrated more myelosuppression than previously untreated patients at 1250 micrograms/m2. No cardiotoxicity was observed. Four objective tumor responses were seen: one complete response in a patient with pelvic recurrence of cervical cancer; one partial response in a patient with cutaneous and lymph gland metastases from head and neck cancer; and two minor responses in patients with liver metastases from colorectal cancer. Plasma concentrations of FCE 23762 and its 13-dihydro metabolite, FCE 26176, were measured in 20 patients at doses > or = 675 micrograms/m2, using HPLC with fluorescence detection. The area under the plasma concentration-time curve ranged from 30 to 80 ng/h/ml; plasma data suggested linear kinetics in the range of tested doses (although there was considerable interpatient variability). The maximum tolerated dose defined in this study using this schedule is 1500 micrograms/m2. A safe phase II dose for previously untreated patients using this schedule is 1250 micrograms/m2; however, this may actually be below the optimal dose for this patient population.

Adult↗
PubMed1995

Ruptured infected popliteal artery aneurysm.

We describe an unusual presentation of an infected popliteal aneurysm. To our knowledge rupture of an aneurysm associated with Salmonella at this site has not previously been reported. The management of infected aneurysms is discussed.

Aged↗
PubMed1995

Reflex sympathetic dystrophy: changing concepts and taxonomy.

We present a revised taxonomic system for disorders previously called reflex sympathetic dystrophy (RSD) and causalgia. The system resulted from a special consensus conference that was convened on this topic and is based upon the patient's history, presenting symptoms, and findings at the time of diagnosis. The disorders are grouped under the umbrella term CRPS: complex regional pain syndrome. This overall term, CRPS, requires the presence of regional pain and sensory changes following a noxious event. Further, the pain is associated with findings such as abnormal skin color, temperature change, abnormal sudomotor activity, or edema. The combination of these findings exceeds their expected magnitude in response to known physical damage during and following the inciting event. Two types of CRPS have been recognized: type I, corresponds to RSD and occurs without a definable nerve lesion, and type II, formerly called causalgia refers to cases where a definable nerve lesion is present. The term sympathetically maintained pain (SMP) was also evaluated and considered to be a variable phenomenon associated with a variety of disorders, including CRPS types I and II. These revised categories have been included in the 2nd edition of the IASP Classification of Chronic Pain Syndromes.

Causalgia↗
PubMed1995

Pathologic duodenogastric reflux associated with persistence of symptoms after cholecystectomy.

BACKGROUND: The aim of this study was to determine whether increased duodenogastric reflux contributes to postcholecystectomy symptoms. METHODS: Gastric pH monitoring, hepatobiliary scintigraphy, gastric emptying scans, and gastric acid analysis were performed in asymptomatic (n = 10) and in symptomatic (n = 27) patients after cholecystectomy. Normal subjects (n = 20), patients with dyspepsia related to gastric acid hypersecretion (n = 20), patients with reflux gastritis after gastric surgery (n = 10), and patients with confirmed primary pathologic duodenogastric reflux (n = 10) were studied as controls. Symptomatic patients also underwent upper gastrointestinal endoscopy. RESULTS: Symptomatic patients had significantly increased interprandial gastric exposure to pH < 3 compared with asymptomatic subjects, which correlated well with a high incidence of hepatobiliary scans positive for abnormal duodenogastric reflux and chronic gastritis on endoscopy. Gastric alkaline exposure in symptomatic patients was similar to that seen in patients with primary pathologic duodenogastric reflux and patients with duodenogastric reflux related to gastric surgery. Gastric acid secretion and gastric emptying were not altered. Five patients tested before and after laparoscopic cholecystectomy showed that nocturnal gastric alkalization was enhanced after operation. CONCLUSIONS: This study suggests that excessive duodenogastric reflux may be responsible for persistence of symptoms after cholecystectomy.

Adult↗
PubMed1995

Evaluation of a modified BACTEC method to study the activity of disinfectants against Mycobacterium tuberculosis.

SETTING: BACTEC radiometry could provide a useful tool for evaluating the effect of disinfectants on mycobacteria. OBJECTIVE: The aim of this study was to improve the recovery of mycobacteria in the BACTEC system and thereby develop a new method for disinfectant testing with Mycobacterium tuberculosis. DESIGN: Protein was added to BACTEC 7H12B media. Growth and the recovery of M. tuberculosis after exposure to disinfectants was measured using viable counts and BACTEC radiometry. RESULTS: Protein additives enhanced growth in 7H12B media. After serial dilution of inoculum, 7H12B plus 10% egg yolk recovered mycobacteria from a 10(-2) higher dilution than viable counts. After 5 min disinfection with 3% peroxygen compound (Virkon), 3% Virkon plus saline or 2% gluteraldehyde (Cidex) no mycobacteria were recovered using standard 7H12B. However, using 7H12B plus protein, growth was detected in all of these within 30 days. In contrast, viable counts detected growth with Cidex and Virkon after 5 min disinfection but not from Virkon in saline. Viable counts took 3-8 weeks to determine. CONCLUSION: Using this modified BACTEC system for the evaluation of disinfectant action on mycobacteria provides advantages in speed, sensitivity and ease of use when compared with viable counts.

Culture Media↗
PubMed1995

Hepatic venous outflow obstruction in patients with polycystic liver disease: pathogenesis and treatment.

Polycystic liver disease is commonly asymptomatic but may present with hepatomegaly, abdominal distension, and dull abdominal pain. Transudative ascites is a rare manifestation in these patients but may occur when portal hypertension is present resulting from associated hepatic fibrosis or after deroofing procedure of a cyst. Exudative ascites might suggest hepatic venous outflow obstruction. Four cases are described where hepatic venous outflow obstruction occurred in patients with polycystic liver disease. Three patients had orthotopic liver transplantation and one had a mesocaval shunt. Of the two patients that survived orthotopic liver transplantation both have shown considerable improvement in their symptoms. None of the patients had any confirmed procoagulant disorder. The mechanism of hepatic venous outflow obstruction in these patients seems to be mechanical compression of hepatic veins by the cysts and associated formation of thrombi in small hepatic vein tributaries. Patients with severe polycystic kidney/liver disease are at risk of hepatic venous outflow obstruction and the onset of this complication is heralded by tender hepatomegaly and presence of exudative ascites.

Adult↗
PubMed1995

Acute gonococcal arthritis: an unusual host and pathogen combination.

A 76 year old man was admitted for evaluation and treatment of acute oligoarticular arthritis having recently returned from India. He was diabetic on admission. Neisseria gonorrhoeae was isolated from pus collected by arthrocentesis of his right knee and was subsequently found to be chromosomally resistant to penicillin. The isolate required proline for growth and expressed the protein 1B-1 serovar. These characteristics of host and pathogen are atypical in that gonococcal arthritis usually occurs in young women and is usually caused by N gonorrhoeae isolates exhibiting hypersusceptibility to penicillin, the arginine, hypoxanthine and uracil requiring auxotype, and the protein 1A serotype. The patient responded well to therapy with oral ciprofloxacin and initial high dose penicillin.

Acute Disease↗
PubMed1995

Characterization of Na(+)-phosphate cotransporters in renal cortical endosomes.

To determine the role of membrane recycling in proximal tubular P(i) transport, we studied the transport functions of simultaneously prepared rat renal cortical endosomal vesicles (EV) and brush-border membrane vesicles (BBMV). Initial P(i) uptake was Na+ gradient-dependent in both vesicles. Kinetic studies showed a lower apparent maximal rate (Vmax) for P(i) uptake in EV compared with BBMV (446 +/- 69 vs. 1493 +/- 117 pmol.mg protein-1 x 15 s-1, respectively; n = 4, P < 0.05), with no difference in the apparent Michaelis constant (Km). Endosomal Na(+)-P(i) cotransport was inhibited by phosphate analogues, phosphonoformic acid and arsenate, but not by the anion-exchange inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Na(+)-P(i) cotransport was electroneutral in both vesicles, with a stoichiometry of 2 for BBMV and 1 for EV. The nonpermeant sulfhydryl reagent, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), produced a marked inhibition of Na(+)-P(i) cotransport in EV but not in BBMV, suggesting accessible sulfhydryl groups, an "inside-out" orientation in EV, and "right-side-out" orientation in BBMV. The EV and the BBMV differed significantly in their phospholipid composition and lipid fluidity. The Na(+)-P(i) cotransporter protein (NaPi-2) abundance, determined by Western blots, was five times lower in EV than in BBMV (0.25 +/- 0.05 vs. 1.36 +/- 0.20 arbitrary units). Renal cortical endosomes contain Na(+)-P(i) cotransporters, albeit at a lower density, suggesting involvement of membrane recycling in the regulation of proximal tubular P(i) transport.

Animals↗