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Biomedical subjects

A A Peters

Publications and source records attributed to A A Peters.

At least 19 recordsLinked to original sources

A monoclonal antibody to CD11d reduces the inflammatory infiltrate into the injured spinal cord: a potential neuroprotective treatment.

The accumulation of inflammatory cells in the lesion of a spinal cord injury (SCI) enhances secondary damage, resulting in further neurological impairment. High-dose methylprednisolone (MP) treatment is the only accepted treatment for inflammation secondary to human SCI but is minimally effective. Using a rat SCI model, we devised an anti-inflammatory treatment to block the infiltration of neutrophils and hematogenous monocyte/macrophages over the first 2 days postinjury by targeting the CD11dCD18 integrin. Anti-CD11d mAb administration following SCI effectively reduced neutrophil and macrophage infiltrate into lesions by 70% and 36%, respectively, over the first 72 h post-SCI. MP also reduced neutrophil and macrophage infiltrate by 60% and 28%, respectively, but by different mechanisms. The immunosuppression caused by anti-CD11d treatment was not sustained, as inflammatory cell numbers were not different from those observed in untreated SCI control animals at 7 days postinjury. In contrast, in MP-treated animals, the number of macrophages was still suppressed in the lesion while neutrophil numbers were significantly increased. These results suggest that anti-CD11d mAb treatment following SCI will minimize the destructive actions associated with early, uncontrolled leukocyte infiltration into the lesion while permitting the positive wound healing effects of macrophages at later time points.

Animals↗

Tumor diameter and volume assessed by magnetic resonance imaging in the prediction of outcome for invasive cervical cancer.

OBJECTIVE: The aim of this study was to evaluate the predictive value of pretherapeutic magnetic resonance imaging (MRI)-based measurements of tumor diameter and volume with regard to recurrent disease. METHODS: MRI on 0.5- or 1.5-T scanners was performed in 126 consecutive women with invasive carcinoma of the uterine cervix. Initial tumor diameter and volume were determined on T(2)-weighted images; volume was calculated by the standard technique of multiplying the sum of the areas by the slice thickness. Patients were treated by radical surgery, radiotherapy, or a combined approach based on clinical International Federation of Gynecology and Obstetrics (FIGO) stage and individual patient criteria. Clinical data (patient age and FIGO stage), MRI-derived tumor dimensions (diameter and volume), and histological findings (tumor invasion depth and lymph-node involvement) were associated and linked to patient outcome. RESULTS: MRI-based tumor diameter correlated strongly with histological tumor invasion depth and lymph-node status (P < 0.01 and P = 0.01) while tumor volume on MRI was significantly associated only with tumor invasion depth into adjacent tissues (P < 0.01). Univariate analysis demonstrated graphically that MRI-derived tumor diameter and volume and clinical FIGO stage are associated with progression-free survival. Correlation analysis showed a strong association between MRI-derived tumor diameter and volume on MRI (r = 68%, P < 0.01) and also demonstrated a correlation between tumor diameter on MRI and FIGO stage Ib (Ib1 versus Ib2) cervical tumors (r = 46.7%, P < 0.01). CONCLUSION: Tumor diameter and volume, determined by pretreatment MRI examinations, predict progression-free survival for patients with invasive cervical carcinoma. This study demonstrates the value of MRI as an adjunct to clinical evaluation of invasive cervical cancer, providing more complete assessment of morphological risk factors important in patient prognosis and treatment planning.

Adult↗

[Surgical treatment of early stage cervical carcinoma at Leids University Medical Center, 1984-1996: depth of invasion, number and bilaterality of metastatic lymph nodes prognostic for recurrence].

OBJECTIVE: To analyse local tumour parameters of early cervical cancer that might be of prognostic significance for tumour relapse in the pelvis. DESIGN: Retrospective. METHOD: Data were collected from 308 patients who underwent radical hysterectomy and pelvic lymphadenectomy in the years 1984-1996 in the Leiden University Medical Centre, the Netherlands. Treatment policies and operating staff were the same during the study period. The existence of relapse was studied by physical, gynaecological, laboratory and, if indicated, radiological examination. RESULTS: Data on 294 patients were available for analysis. Their mean age was 45 years (range: 21-82). Postoperative radiation treatment was given to 119 patients (40%). Mean follow-up duration was 36 months (range: 1-136). Recurrences had developed in 46 patients (15.6%), 29 of whom had died. The calculated overall 5-year survival rate was 83%; 91% for those with negative and 53% for those with positive pelvic nodes. The calculated recurrence-free-5-year survival rate was 75% for the entire group, 83% for the patients without and 47% for those with lymph node metastases. When more than one lymph node region was affected, 5-year disease free survival was 19% and when lymph node metastasis occurred bilaterally, it was 22%. Multivariate analysis revealed that lymph node involvement (hazard ratio: 4.4), parametrial involvement (5.5), tumour size > 30 mm (4.6) and depth of invasion > 10 mm (5.1) were independent factors of prognostic significance for disease free survival. The current indications for adjuvant treatment might be extended with infiltration depth. The number and the bilaterality, if any, of affected lymph node stations might be indication for additional adjuvant therapy.

Adult↗

The HTLV-I orfI protein is recognized by serum antibodies from naturally infected humans and experimentally infected rabbits.

The mechanism of T-cell transformation by human T-cell lymphotropic virus type I (HTLV-I), though not completely understood, appears to involve the interactions of several viral and cellular proteins. One of these viral proteins, p12(I), encoded by HTLV-I orfI, is a weak oncogene that binds the 16-kDa subunit of the vacuolar ATPase and interacts with the immature beta and gamma(c) chains of the IL-2 receptor. We have expressed the singly spliced orfI cDNA in the baculovirus system and used the recombinant protein as a tool to assess the presence of antibodies in naturally or experimentally infected hosts. In addition, rabbit antisera were raised against various p12(I) synthetic peptides and used to identify three antigenic regions within p12(I), one between the two putative transmembrane regions of p12(I) and two at the carboxy-terminus of the protein. More importantly, sera from a naturally infected human (1 of 32) and experimentally infected rabbits (9 of 20) recognized the rp12(I), demonstrating orfI expression and immunogenicity in vivo. Taken together these data provide the first evidence of orfI expression during HTLV-I infections.

Amino Acid Sequence↗

HTLV type I/II in British Columbia Amerindians: a seroprevalence study and sequence characterization of an HTLV type IIa isolate.

It has been established that the human T cell lymphotropic viruses type I and II (HTLV-I and HTLV-II) are both present in some indigenous peoples of the Americas. While HTLV-I has been identified in coastal British Columbia Indians (BCIs), HTLV-II has not been previously reported in the BCIs or other Canadian Amerindians. The prevalence of HTLV-I and HTLV-II in these populations has not been extensively studied. In this article, we examine a group of BCIs from Vancouver Island who belong to the Nuu-Chah-Nulth and are known to have an increased incidence of rheumatic disease. In 494 serum samples from this tribe, the levels of prevalence of HTLV-I and HTLV-II were 2.8 and 1.6%, respectively. No association could be made between arthropathy and HTLV-I infection. In addition, we characterized an HTLV-II isolate of a BCI from the coastal mainland of British Columbia and with a history of intravenous drug abuse. This case represents the first molecular characterization of a Canadian Amerindian HTLV-II isolate: a subtype IIa virus with phylogenetic affinity for intravenous drug user isolates and containing an extended form of the Tax protein. These results are consistent either with this strain having been sampled from a polymorphic ancestral pool of HTLV-II that gave rise to the current epidemic spread of this virus by intravenous drug use and sexual transmission, or with its being "back-transmitted" into the BC Amerindian population in association with intravenous drug use.

Base Sequence↗

A multi-mutant herpes simplex virus vector has minimal cytotoxic effects on the distribution of filamentous actin, alpha-actinin 2 and a glutamate receptor in differentiated PC12 cells.

To develop effective gene therapy techniques that target populations of neurons in the spinal cord, suitable vectors must be developed that will undergo efficient, retrograde transport from an appropriate peripheral site and will not be cytotoxic. Our previous work (LeVatte et al, 1998a) has demonstrated that a replication defective herpes simplex virus vector 14Hdelta3vhsZ, that has been substantially detoxified, is retrogradely transported from peripheral sites and can infect large numbers of the targeted spinal neurons. We plan to develop targeted gene therapy approaches designed to modulate the excitatory glutamatergic methyl-D-aspartate (NMDA) receptor in spinal cord neurons as a means of ameliorating a form of episodic high blood pressure that occurs after spinal cord injury. In this report, we demonstrate that, in differentiated PC12 cells, a neuronal-like cell line, the virus vector does not appear to alter aspects of the cytoskeletal architecture important to the proper distribution of the NMDA receptor. In turn, the distribution of endogenous NMDA receptor 1 subunit protein (NMDAR1) or a transfected NMDAR1-green fluorescent fusion protein was also found to be unaltered after vector infection. However, whereas endogenous NMDAR1 distribution was maintained, vector infection did tend to reduce the level of its expression. This drop in endogenous NMDAR1 expression coincided with the expression of the HSV immediate early genes ICP0 and ICP27 over the first 24-48 h. These results indicate that the 14Hdelta3vhsZ herpes simplex virus vector is suitable to use in future strategies to alter the level of gene expression in targeted populations of spinal cord neurons.

Actin Cytoskeleton↗

An apparent case of human T-cell lymphotropic virus type II (HTLV-II)-associated neurological disease: a clinical, molecular, and phylogenetic characterisation.

Several studies have reported an association between HTLV-II and a neurological condition which has come to be called HTLV-II-associated myelopathy and is similar, in some cases, to HTLV-I-associated myelopathy. To further explore the establishment of an etiological link between this virus and neurological disease, we determined the HTLV status of three individuals, one of which presented with symptoms of progressive ataxia. Since the patient with neurological disease and her husband were HTLV-II positive, we had the potential to study one of few cases of an HTLV-II-associated neurological disorder, and the first case in Canada. However, although the individual with the neurological disease was HTLV-II positive, we discovered that her brother, who displays the same clinical symptoms, was not positive for either HTLV-II or HTLV-I. Thus, disease association with HTLV-II became unsupportable. We present here, nevertheless, the first sequence and phylogenetic analysis of an HTLV-II isolate in Canada. This study suggests that cases of HTLV-II and neurological disease must be carefully investigated before any etiological conclusions can be made.

Ataxia↗

Flow cytometric DNA analysis with cytokeratin gating of formalin-fixed deparaffinized breast cancer nuclei.

The "gold standard" inflow cytometric DNA analysis of breast cancer uses fresh tumor cells simultaneously labeled for cytokeratin (CK) and DNA. We developed a 2-parameter CK-DNA flow assay suitable for archival, paraffin-embedded tissue (PT). Six anti-CK monoclonal antibodies were tested by immunocytochemistry and our assay for staining of nuclei extracted from PT breast cancers by combination pepsin-trypsin digestion. Clone CAM 5.2 was inadequate for PT nuclear suspensions, but a cocktail of 2 anti-CK clones (AE1/AE3 and KL-1) distinguished epithelial from nonepithelial nuclei in 2-parameter flow dot plots. We studied 82 routine PT breast tumors by our assay and used a univariate flow DNA histogram based on fresh biopsy tissue for comparison. Three histogram data quality indicators were improved. A trend toward higher S-phase fractions was found for DNA diploid PT tumors, although when inflammation was evident histologically, the increment in S-phase fraction with gating was often marked. CK gating identified PT tumors containing concurrent CK-positive DNA diploid and nondiploid populations (27 of 56 DNA nondiploid histograms). By excluding nonepithelial nuclei, 2-color CK-DNA flow methods may increase the accuracy of ploidy and S-phase fraction measurements. Our method appears superior to previous techniques using clone CAM 5.2 for labeling of archival breast cancers.

Antibodies, Monoclonal↗

Is there an effect of perioperative blood transfusion on the outcome of radical hysterectomy with lymphadenectomy for cervical cancer in South Africa?

The aim of this study was to investigate whether there is an effect of perioperative blood transfusion on the outcome of radical hysterectomy with lymphadenectomy for cervical cancer. One hundred and thirty-one patients with cervical cancer were treated by Wertheim radical hysterectomy in the period from 1984-1991. Eighty-six patients received blood transfusions during surgery or within two weeks, whereas 45 patients did not receive any blood transfusion. Transfused and non-transfused patients did not differ with respect to mean age, race, weight, FIGO-stage, cell-type, grade, size, depth of invasion and nodal involvement. Transfused patients had more blood loss, longer surgical time and lower haemoglobin levels. Using log rank analysis, the calculated five-year survival was 81% for the transfused group and 84% for the non-transfused group, a non-significant difference. The five-year disease-free survival rate was 87% for the transfused group and 88% for the non-transfused group. This study suggests that perioperative blood transfusion does not adversely influence survival after the Wertheim operation for cervical cancer.

Adenocarcinoma↗

[Diagnostic and therapeutic dilemmas in malignancy during pregnancy].

In four pregnant women, aged 28, 29, 30, and 35, malignancies were diagnosed: synoviosarcoma, gastric carcinoma, non-Hodgkin B cell lymphoma and undifferentiated adenocarcinoma in one of the labia vulvae, respectively. The first three women eventually died, the first before giving birth, the last woman was treated surgically and was alive without recurrence two years after treatment. Pregnancy can lead to diagnostic dilemma and delay as many symptoms of a malignancy are not recognised as such but are attributed to the pregnant state and because of reluctance to apply diagnostic tools which can be harmful to the foetus. It can also lead to therapeutic dilemma and delay because several therapies may also harm the foetus.

Adult↗

Pain relief during and following outpatient curettage and hysterosalpingography: a double blind study to compare the efficacy and safety of tramadol versus naproxen. Cobra Research Group.

OBJECTIVE: To compare the analgetic efficacy and side-effects of Naproxen and Tramadol following the outpatient VABRA aspiration or hysterosalpingography. SETTING: Ninety-one patients from the gynaecology clinics of two university hospitals and one municipal-teaching hospital. DESIGN: Multicentre double blind randomized clinical trial. Computerised randomisation, stratification per-centre. METHODS: Semiquantitative assessment of the two drugs was performed by the patient and the gynaecologist using a 1- to 6-point scale. Pain, stress and well-being was scored by the patient using the visual analog scale (VAS) and the verbal description scale (VDS), ranging from 0 (good) to 100 (bad). Side-effects during the first 24 h postoperatively were recorded by the patient in a diary. RESULTS: The analgetic efficacy (pain, stress and well-being) of Naproxen and Tramadol was identical. Subjective assessment by the patient and the doctor also revealed no differences between Naproxen and Tramadol. Side-effects of Tramadol, however, were significantly more severe than those of Naproxen and this phenomenon was responsible for a lower ability to proceed with normal activities in the Tramadol group. CONCLUSION: Tramadol is a good alternative for Naproxen at outpatient VABRA or HSG procedures when Naproxen is contra-indicated.

Adult↗

The place of Zoladex in deferred surgery for uterine fibroids. Zoladex Myoma Study Group.

Two hundred and forty-seven patients with uterine fibroids were randomized to surgery alone or 3 months' Zoladex (Zeneca, Macclesfield, Ches., UK) followed by surgery. Zoladex significantly reduced uterine and fibroid volumes (p = 0.0001). There was a significantly (p = 0.002) greater mean rise in haemoglobin from entry to preoperation in the Zoladex group (1 g/dl) compared with the surgery-alone group (0.3 g/dl) as well as a tendency towards easier surgery, and reduced operative blood loss. Zoladex-treated patients had a significantly (p = 0.016) shorter hospital stay and pelvic pain and abdominal pressure symptoms were significantly (p < 0.0001) reduced in this group. Zoladex was well tolerated.

Adult↗

Metastasis of breast carcinoma to a primary mucinous cystadenocarcinoma of the ovary.

A case of a patient with breast cancer metastatic within the tumor stroma of a primary ovarian carcinoma is presented. This finding is to the best of our knowledge the first case reported. The encountered diagnostic problems are discussed. A distinct peroperative frozen section diagnosis on the large, cystic, partially necrotic ovarian mass was not possible because of sampling problems. A comparable immunohistochemical staining pattern of cells being CEA negative, OC-125 negative, and HMFG-1 positive was found in both the primary breast tumor and in the solid epithelial parts in the tumor stroma of the left-sided ovarian carcinoma, as well as in the stroma of the right ovary. Immunohistochemical findings in the left-sided epithelial cystic ovarian tumor showed, as expected, apical reactivity with antibodies directed against CEA, whereas OC-125 and HMFG-1 were negative. Ploidy analysis showed that the primary breast carcinoma and the stromal part of left ovarian malignancy had the same aneuploid stemlines (DNA index = 1.18). The epithelial lining of the cystic ovarium carcinoma not showing the presence of metastatic lesion in the stroma showed the presence of a diploid GO,1 population only. These results show that DNA flow cytometry and immunohistochemistry may be helpful in assessing the origin of the malignancies in this unusual double presentation of both metastatic breast cancer and primary ovarian carcinoma.

Aneuploidy↗

The absence of human papilloma virus (HPV) related parameters in sexually non-active women.

In to order to investigate the prevalence of HPV related parameters in sexually non-active women, smears of 75 virgins were microscopically reviewed for alterations caused by HPV i.e. koilocytosis, parakeratosis and multinucleinization. In none of these smears were the mentioned parameters seen together, so the diagnosis of HPV infection could not be assessed. In an age-matched control population consisting of 75 sexually active women smears were reviewed. In this group 10 smears (13%) were found positive for HPV infection, well in accordance with literature.

Adolescent↗

A comparison of pefloxacin/metronidazole and doxycycline/metronidazole in the treatment of laparoscopically confirmed acute pelvic inflammatory disease.

A double-blind, randomised study was conducted to compare the efficacy and safety of a combination of pefloxacin and metronidazole versus doxycycline and metronidazole in patients with pelvic inflammatory disease (PID). The clinical diagnosis had to be confirmed by laparoscopy before patients were included. Of the 74 patients who fulfilled the clinical criteria for PID, laparoscopy confirmed the diagnosis in only 40 patients (54%). The microorganism most frequently found as causative pathogen was Chlamydia trachomatis. Both treatment groups showed a good response to the study-medication. At discharge 9 patients in the pefloxacin group (45%) were cured and 10 patients (50%) had improved. In the doxycycline group 7 patients (35%) were cured and 10 patients (50%) had improved. Obviously pefloxacin/metronidazole and doxycycline/metronidazole are equally effective in the treatment of PID.

Acute Disease↗

[Morbidity and results of 100 radical hysterectomies performed in an oncology center].

One hundred consecutive radical hysterectomies performed in a Dutch oncology centre during a five and a half year period between 1984 and 1990, were analysed. The operations were performed in a uniform manner by the same three surgeons. Surgical mortality was nil. Mean operating time was 4 hours and mean blood loss amounted to 1200 ml. One patient developed a vesicovaginal fistula. Long lasting urinary symptoms occurred in 32% of patients, sex problems in 13%. The latter situation was encountered significantly more frequently when surgery was combined with radiotherapy. Eighty-two of the 100 patients had a primary cervical carcinoma and were analysed further. Distribution according to stage was as follows: stage IA: 3, IB: 64, IIA: 13, IIB: 2. Postoperative external and intracavitary pelvic radiation was given in 34 patients (41%). Three-year survival of these patients amounted to 86%. One-third of patients had a large primary tumour (diameter greater than 4 cm). Three-year survival rate in this subgroup of patients was 78%. Lymph node metastases were found in 14 patients (17%). Three-year survival rates for patients with and without lymph node metastases were 64% and 94%, respectively (p less than 0.0001). Results and complications of this series were compared with the current literature data and found to be comparable and sometimes even better than recent literature data. These findings may serve to advocate further centralisation of this kind of surgery in oncological centres in the Netherlands.

Adolescent↗