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Biomedical subjects

D Packham

Publications and source records attributed to D Packham.

18 recordsLinked to original sources
PubMed2004

Phase I clinical trial of a human idiotypic p53 vaccine in patients with advanced malignancy.

BACKGROUND: The purpose of this study was to induce immunity to p53 by using an idiotypic vaccine, composed of a pool of eight peptides derived from the complimentarity determining regions (CDRs) of human anti-p53 antibodies. PATIENTS AND METHODS: Subjects with advanced malignancy received up to four, monthly intradermal injections of pooled peptides (500 microg of each) admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 microg). In addition, two sheep and two rabbits were also vaccinated with the pooled peptides. RESULTS: Fourteen subjects were enrolled into the study and six of these completed the vaccination schedule. The vaccine was well tolerated by all subjects and no major adverse events were attributable to the vaccine. All subjects mounted in vivo delayed type hypersensitivity (DTH) responses to two or more of the individual vaccine peptides. Vaccine-induced antibodies specific for peptides 2, 5 or 8 were detected in four of six subjects, and two of these had vaccine-specific, cell-mediated responses. Increasing titers of p53-specific antibodies were found in one patient. No T-cell response to p53 was observed in any of the subjects. All animals developed humoral immunity to the peptides and one of the sheep developed rising serum titers of anti-p53 antibodies. CONCLUSIONS: Vaccination with human antibody CDR regions represents a novel method for inducing human antibodies, which may in turn serve as immunological mimics of p53.

Adult↗
PubMed2001

In vitro HIV-specific CTL activity from HIV-seropositive individuals is augmented by interleukin-12 (IL-12).

IL-12 production is reduced in HIV infection, and recombinant human IL-12 (rhIL-12) augments in vitro HIV-specific proliferative responses in PBMC from HIV-seropositive individuals. To determine whether rhIL12 could also augment HIV-specific CTL responses we studied 41 HIV-seropositive individuals. Recombinant hIL-12 increased the detectable in vitro HIV-specific CD8 CTL activity of PBMC taken from HIV-seropositive individuals with CD4 counts >500 cells/microl and from some individuals with lower CD4 counts. IL-12 increased cell recovery in cultures of PBMC from HIV-seropositive individuals with CD4 counts >500 cells/microl and also increased the precursor CTL frequency. However, the increase in HIV-specific CTL activity was not due to IL-2 or IFN-gamma production or an increase in the number of cells with surface markers characteristic of CTL effector cells. This study demonstrates that rhIL-12 augments in vitro HIV-specific CTL activity and provides evidence to justify further investigation within clinical trials of this cytokine in HIV infection.

Adult↗
PubMed2001

Time trends in HIV incidence among homosexually active men seen at sexual health clinics in Australia, 1993-1999.

BACKGROUND: Increases in sexual risk behaviour have recently been reported among homosexually active men in Australia and in other industrialised countries, potentially facilitating an increase in HIV incidence. OBJECTIVE: To monitor HIV incidence among homosexually active men seen through a network of sexual health clinics in Australia. STUDY DESIGN: Selected metropolitan public sexual health clinics provided counts of the number of people seen at the clinics during a calendar year, the number voluntarily tested for HIV antibody and the number newly diagnosed with HIV infection, broken down by sex, age group, HIV exposure category and HIV antibody testing history. HIV incidence was estimated among homosexually active men with a history of a negative test in the 12 months prior to last being seen in a calendar year. RESULTS: Of 23924 men seen at the clinics in 1993-1999 with a reported history of male homosexual contact, 7440 (31.1%) had a negative test in the 12 months prior to last being seen in a calendar year. The percentage of men with a recent negative test declined significantly over time, from more than 33% in 1994-1996 to 29% in 1999 (P=0.003), and with increasing age, from 34.3% among men aged 25-29 years to 27.4% among men aged 40 years or older (P<0.0005). A total of 5346 (71.9%) men were retested for HIV antibody within 12 months of the last negative test. The percentage of men retested declined significantly over time, from 77.8% in 1994 to 67.2% in 1999 (P=0.021) but did not change by age group (P=0.132). Overall, 56 men were newly diagnosed with HIV infection. Estimated HIV incidence was 2.1% in 1993-1999; incidence did not change significantly by year (P=0.498) or age group (P=0.757). CONCLUSION: HIV incidence has remained stable among homosexually active men seen through a network of sexual health clinics in Australia.

Adolescent↗
PubMed2000

Phase I clinical trial of the chimeric monoclonal antibody (c30.6) in patients with metastatic colorectal cancer.

The murine antibody 30.6 recognizes an antigen that is expressed on a high proportion of colorectal carcinomas and their metastases. We report the results of single-dose escalation studies of the chimeric 30.6 (c30.6) monoclonal antibody in metastatic colorectal cancer, to evaluate its safety, pharmacokinetics, and biodistribution. Recombinant c30.6 (IgG1kappa) antibody was secreted from Chinese hamster ovary cells and purified by a multistep chromatography process. Seventeen patients with metastatic colorectal cancer were enrolled in this dose escalation study. The first four patients were treated with 3 mg of 123I-labeled c30.6, whereas the next 13 received a single dose of unlabeled antibody (maximum dose, 50 mg/m2). The most frequent side effect was a novel syndrome of severe burning and erythema of the face, chest, neck, ears, palms, soles, and genitalia. The frequency of this syndrome was markedly reduced in those patients premedicated with high doses of histamine receptor 1 and histamine receptor 2 blockers. Other side effects were mild and predictable. Biodistribution studies showed a rapid and intensive hepatic uptake. At the 50 mg/m2 level the half-life and maximum serum concentration were 81 +/- 15 h and 7.9 microg/ml, respectively. One patient developed a low-level human anti-c30.6 response. Tumor response was assessed by computed tomography, positron emission tomography scanning, and serial carcinoembryonic antigen measurements. There were no partial responses, although positron emission tomography scanning demonstrated some reduction in tumor activity in three individuals. The chimerized c30.6 antibody is not immunogenic in humans and appears worthy of further study. It does, however, produce a unique profile of side effects that can be well controlled with premedication.

Adult↗
PubMed1998

Lambda light chain induced nephropathy: a rare cause of the Fanconi syndrome and severe osteomalacia.

The Fanconi syndrome is a generalized disorder of proximal renal tubular transport characterized by wasting of phosphate, amino acids, glucose, bicarbonate, and uric acid. The association of the acquired Fanconi syndrome with lambda light-chain proteinuria is rare. We report the third case in the English language literature. A 65-year-old man presented with severe pelvic pain. Investigations showed an elevated serum creatinine level, and a 24-hour urine collection contained 2.56 g protein. The Fanconi syndrome was diagnosed, with findings of phosphaturia, glycosuria, and aminoaciduria. Bence Jones protein (lambda sub-type) was present in the urine at a concentration of 0.58 g/L. Monocytic cells in the bone marrow and proximal tubular cells in the kidney contained cytoplasmic crystalline inclusions. Undecalcified bone sections confirmed the clinical diagnosis of osteomalacia. The patient was treated with phosphate, calcium, and ergocalciferol and experienced significant symptomatic improvement. The Fanconi syndrome caused by light-chain deposition in proximal tubular cells is well described in the literature. However, it is rare for the light chains to be of the lambda subtype. This may reflect differences in the physicochemical properties of kappa and lambda light chains.

Aged↗
PubMed1996

Pregnancies resulting from embryos biopsied for preimplantation diagnosis of genetic disease: biochemical and ultrasonic studies in the first trimester of pregnancy.

PURPOSE: Our purpose was to investigate early biochemical and ultrasonic measurements of pregnancies resulting from embryos biopsied for preimplantation diagnosis of inherited disease. RESULTS: Singleton pregnancies following biopsy had lower initial hCG levels [10 or 12 days after oocyte recovery (OR)], which rose steeply to match the controls by 16 days after OR. Twin biopsied pregnancies showed hCG levels lower than those of twin control pregnancies, which rose in parallel with the controls but remained lower for a longer period than the singletons. Progesterone levels showed a wide variation. Ultrasound measurements showed that overall the mean sac diameter and crown-rump length at 28 and 42 days after egg collection were similar in biopsied and control pregnancies. CONCLUSIONS: Pregnancies resulting from biopsied embryos behave similarly to control IVF pregnancies. However, the reduction in cell mass following embryo biopsy occasionally results in reduced levels of circulating serum hCG and smaller ultrasound measurements in early pregnancy.

Biopsy↗
PubMed1991

Five cases of neurocysticercosis diagnosed in Sydney.

Cysticercosis, once rare in Australia, is now more frequently diagnosed. This change reflects the countries of origin of new immigrants and the destinations of Australians travelling. Five cases of neurocysticercosis diagnosed at Westmead Hospital in Sydney are described. Two involved Australians, a father and son who had visited eastern and southeastern Asia 10 years before presentation. The other three included immigrants from Chile and India and a visitor from Timor. Ages ranged from 5 to 57 years. Three individuals presented after focal seizures involving the upper limb, one had a long standing history of neurological dysfunction and one suffered from persistent headaches. In all cases computed tomographic scanning (CT) or magnetic resonance imaging (MRI) revealed cystic brain lesions and three of the five were seropositive as well. Four were treated with praziquantel and in one the lesions regressed significantly following treatment. However, the lesion in one case had decreased in size prior to treatment and that in the untreated individual also became smaller.

Adult↗
PubMed1990

The turtle's revenge: a case of soft tissue Mycobacterium chelonae infection.

A case of cutaneous Mycobacterium chelonae infection with sporotrichoid spread and extensive antibiotic resistance is presented. Control of this problem was only achieved after extensive debridement and grafting of the involved limb. The importance of surgery in management is discussed and the literature is reviewed.

Aged↗
PubMed1988

Histological features of IgA glomerulonephritis as predictors of pregnancy outcome.

116 pregnancies undertaken by 70 women with IgA glomerulonephritis and their diagnostic renal biopsies have been reviewed. An IgA diffuse mesangial proliferative lesion with superimposed focal and segmental proliferative lesions (IgA FSP) on diagnostic renal biopsy was associated with a greater incidence of maternal complications than IgA diffuse mesangial proliferative glomerulonephritis with no superimposed lesions (IgA DMP) and IgA diffuse mesangial proliferative glomerulonephritis with superimposed focal and segmental hyalinosis and sclerosis (IgA FSHS) (p less than 0.025). Patients with severe vessel lesions had a significantly greater incidence of fetal loss than those with only mild to moderate lesions (p less than 0.025).

Abortion, Habitual↗
PubMed1987

Renal biopsy: indications and complications in pregnancy.

A series of 111 renal biopsies performed in 104 pregnant women during the past 20 years at The Royal Melbourne Hospital and Royal Women's Hospital, Melbourne were reviewed. The indications for biopsy and the histological findings are detailed. The complication rate was very low (4.5%). It is concluded that the procedure is safe and that renal biopsy during pregnancy yields a definitive histological diagnosis in almost all cases. The indications for renal biopsy in pregnancy are discussed.

Biopsy↗
PubMed1986

Herpes simplex encephalitis in infants.

Two cases are reported of severe encephalitis in infants that were caused by a primary infection with herpes simplex virus type 1. Both patients presented with focal seizures; the clinical diagnosis was confirmed by the rapid appearance of IgM antibody to herpes simplex virus type 1 in cerebrospinal fluid and serum. In spite of the early use of acyclovir, which was administered by the intravenous route, the clinical response was poor and both infants were left with severe neurological impairment.

Acyclovir↗
PubMed1986

An assessment of the possible protective effect of allopurinol in acute stroke.

Allopurinol has been shown to have a protective effect on ischaemic tissue by the indirect prevention of excessive purine loss. This property was tested in the gerbil model of acute stroke. A total of 69 animals were pretreated with an intraperitoneal injection of either allopurinol (50 mg/kg) or sterile water and then subjected to unilateral ligation of the left common carotid artery under general anaesthesia. The clinical effect of the ligation was grouped into three categories of normal, mild to moderate defect (splayed leg, turning behaviour) and severe defect (death, nonresponsiveness and seizures). More normal animals and fewer severely affected animals were present in the allopurinol treated group compared to controls, but only at 2 to 4 hours after carotid ligation (p less than 0.05). Histological examination of brain tissue from the normal category failed to reveal any difference in subclinical ischaemic damage between the two groups. It was concluded that allopurinol may have a protective effect in acute stroke and that this property warrants further elucidation.

Acute Disease↗
PubMed1985

Prevention of herpesvirus infections in renal allograft recipients by low-dose oral acyclovir.

Forty patients with serum antibody against herpes simplex virus (HSV) were enrolled in a randomized, placebo-controlled, double-blind investigation of acyclovir given orally in a low dosage as prophylaxis against recurrent HSV infection after renal transplantation. During 30 postoperative days of medication, 14 of 21 placebo-treated and one of 19 acyclovir-treated patient(s) developed reactivation of HSV infection. Eleven of the former, but not the latter, had herpetic lesions. The protection against active infection with HSV during the period of prophylaxis with acyclovir is statistically highly significant. From 30 to 90 days after transplantation when no antiviral medicine was given, 60% (3/5) of the remaining placebo recipients and 44% (7/16) of the acyclovir patients developed active HSV infections. Herpetic lesions occurred in two of three and two of seven of infected people in the respective groups. No adverse effects of the drug were observed. The results show that HSV infections in immunosuppressed renal allograft recipients can be safely prevented, deferred, and ameliorated by an initial period of prophylaxis with a low dose of oral acyclovir.

Acyclovir↗
PubMed1979

Renal reflux, scarring, cystometrography and tissue types.

Four families with a variety of renal tract abnormalities including reflux, cortical scars, atrophy and duplex systems are described. Cystometrograms in eight with reflux and scars did not show any evidence of outflow high pressure systems. Tissue typing was carried out in a proportion of affected and unaffected family members, and with the addition of another reported family that had been tissue typed, showed an increase in A9, B8 and homozygosity in the families with these abnormalities. A retrospective survey of transplanted patients with tissue type A9 showed a higher prevalence of pyelonephritis and associated abnormalities than other diseases leading to end stage renal failure.

Cicatrix↗
PubMed1968

A touch-detecting teaching machine with auditory reinforcement.

This teaching machine has been designed and used to train reading and other visual discrimination skills with normal and retarded children. On each frame the subject responds by touching one of three response panels on which are projected the multiple-choice alternatives. The response panels are coated with a transparent conducting film which allows electronic detection of this simple and direct response. Correct responses are reinforced by the machine naming the stimulus, while auditory reinforcement is absent for an incorrect response. The subject's performance level is continuously computed as an exponentially weighted moving average. The measure is weighted so that it rapidly follows recent changes in performance.

Journal Article↗