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P A Sillevis Smitt

Publications and source records attributed to P A Sillevis Smitt.

At least 19 recordsLinked to original sources
PubMed2000

Intra-CSF administered recombinant adenovirus causes an immune response-mediated toxicity.

High doses of adenotk were injected into the cerebrospinal fluid of rats and nonhuman primates (Macaca mulatta). Vector administration was followed by ganciclovir administration for 14 days. Despite the absence of clinical symptoms, analysis of the cerebrospinal fluid (CSF) and histopathological examination of the central nervous system (CNS) of the monkeys (3 weeks after vector injection) were consistent with a viral meningitis. Immunohistochemical analysis of the inflammatory infiltrates in the monkeys revealed the presence of T and B lymphocytes, indicating a combined cellular and humoral immune response to the vector. This latter was supported by the finding of intrathecal anti-adenovirus antibody synthesis. Rats receiving high intrathecal adenotk doses showed a transient and dose-dependent clinical toxicity consisting of lethargy, hyperemic eyes and weight loss. Histopathological examination of the meninges showed a shift from polymorphonuclear infiltrates during the first post-injection days to clusters of mononuclear cells after 7 days. Acute toxicity is probably related to the early, innate immune response to the vector. In a separate experiment, high levels of IL-8 and IL-6, were measured during the first 2-3 post-injection days in the CSF of two monkeys which received intrathecal adenoLacZ. Therefore, these cytokines seem to play an important role in initiating the nonspecific immune response. In one monkey which received adenotk, recombinant adenovirus was cultured from serum samples obtained at the 7th post-injection day. At this time-point, no vector could be isolated from CSF samples. Based on these preclinical data, we recommend careful dose finding for clinical studies that aim to treat patients with leptomeningeal metastases.

Adenoviridae↗
PubMed1999

[Towards an accreditation system for the Dutch hospitals].

The development of the Netherlands system for accreditation of hospitals started in 1989 in the Pilotproject Accreditation (PACE). This resulted in the establishment of the Netherlands Institute for Accreditation of Hospitals (NAIH) early 1999, by the Dutch Association of Hospitals, the Dutch Association of University Hospitals, the Dutch Organisation of Medical Specialists and the PACE foundation. Dutch hospitals may request (voluntary) for an accredition for their whole organisation or for parts of it, independent of the used quality system. An accreditation assesses whether organizational requirements are available for quality assurance. Accreditation is not primarily aimed to account for organizational quality, but rather to find points for improvement. The survey is carried out by peers: experts from other Dutch hospitals. The frame of reference used in accreditation is composed of 35 departmentwise standards and a hospitalwide standard 'Quality system'. All standards are developed by people in Dutch hospitals. NIAH can accept certificates for parts of the hospital (e.g. laboratoria) issues by organisations. The system is complementary to the 'visitities' which are organized by the medical specialist societies in the Netherlands. From 1996-1998 trial accreditations were carried out in 19 Dutch hospitals. These showed that the accreditation system has an added value for Dutch hospitals.

Accreditation↗
PubMed1999

Negative sural nerve biopsy in neurolymphomatosis.

Patients with non-Hodgkin's lymphoma occasionally develop widespread invasion of peripheral nerves by tumor cells or neurolymphomatosis (NL). Clinically this usually results in asymmetrical, progressive, and painful polyneuropathy. Diagnosis rests on the identification of tumor cells in peripheral nerves. To avoid false-negative biopsy findings in patients with malignant lymphomatous infiltration of peripheral nerves it has been recommended to biopsy clinically involved nerves. We present two patients with histologically confirmed NL in whom sural the nerve biopsy finding was negative despite clinical and neurophysiological evidence of involvement of the sural nerve a. The clinical features of NL are reviewed. Some patients with neurolyphomatosis have only focal or proximal involvement of nerves, requiring the biopsy of an affected part of these nerves. Magnetic resonance imaging may be useful in identifying affected nerves.

Adult↗
PubMed1999

Phase II study of weekly dose-intensified cisplatin chemotherapy with oral etoposide in recurrent glioma.

BACKGROUND: In most patients with recurrent glioma chemotherapy is the only remaining treatment option. In general results of chemotherapy in these patients are poor, and trials on new regimens are indicated. Because relatively good results have been achieved with combinations of platin compounds and etoposide, we investigated a dose-intensified cisplatin regimen with oral etoposide. METHODS: Eligible patients, with recurrent glioma after surgery and radiation therapy were treated with two four week-cycles with cisplatin 70 mg/m2 on days 1, 8 and 15, combined with oral etoposide 50 mg daily on days 1-15. In responding or stabilized patients, treatment was continued with six four week-cycles of oral etoposide 50 mg/m2 on days 1-21. Toxicity was assessed using the NCI Common Toxicity Criteria, a 50% decrease in contrast enhancing area on MRI scan was considered a partial response. Time to progression was measured from the start of chemotherapy. RESULTS: Sixteen patients were included, 11 were progressive during or immediately after the induction cycles. Two patients achieved a partial response with a time to progression of 42 and 58 weeks. Three patients were stable for 11, 14 and 15 weeks respectively. Toxicity was modest. DISCUSSION: This dose-intensified cisplatin regimen did not result in a significant number of objective responses and even the number of 'stable disease' was small. Given the low response rate of this intensive treatment, we consider this intensive regimen inappropriate for these patients.

Adult↗
PubMed1999

Leptomeningeal metastasis after surgical resection of brain metastases.

OBJECTIVE: To determine the incidence and risk factors for leptomeningeal metastasis after surgery for brain metastasis of solid tumors. METHODS: Review of the records of all patients operated on for brain metastasis between January 1990 and August 1995. RESULTS: In this period 28 patients underwent surgery for brain metastasis, of whom 27 were available for evaluation in this study. Median survival after craniotomy was 11 months. Nine patients (33%) developed leptomeningeal metastasis 2-13 months after surgery, which included six of the nine patients operated on for posterior fossa metastasis (p=0.05). In five patients, leptomeningeal metastasis was the only site of recurrence. Three patients developed the leptomeningeal metastasis as bulky tumour along the spinal cord, which is a rare presentation. No other risk factors for the development of leptomeningeal metastasis other than surgery for posterior fossa metastasis were identified. CONCLUSIONS: There is an increased risk of leptomeningeal metastasis after surgery for posterior fossa metastasis. Future trials should consider the value of an active approach to this complication in these patients.

Adult↗
PubMed1998

[Clinical thinking and decision making in clinical practice. A patient with systemic lupus erythematosus and behavioral changes].

A 48-year-old man with systemic lupus erythematosus (SLE) was admitted with fever, headache and mental change. On admission he was treated with daily doses of cyclophosphamide 100 mg and prednisone 7.5 mg. Orientation and attention were diminished and visual examination revealed right-sided homonymous hemianopia. MRI of the brain showed a ring-enhanced, space occupying lesion in the left occipital lobe. An infectious disease cause was considered, because disease activity parameters of SLE were all negative (anti-dsDNA and the complement profile). The anti-Toxoplasma titre was elevated in cerebrospinal fluid (57 IU/ml) and in serum (1140 IU/ml), both IgG. A tentative diagnosis of Toxoplasma encephalitis was made and a trial anti-toxoplasmosis treatment with pyrimethamine and sulfadiazine was administered. Two weeks later the patient was normal at neurological examination and his brain MRI had greatly improved. The anti-Toxoplasma titre had dropped significantly.

Diagnosis, Differential↗
PubMed1998

Intracerebral injection of adenovirus harboring the HSVtk gene combined with ganciclovir administration: toxicity study in nonhuman primates.

A high dose (1-2.5 x 10(10) infectious units) of recombinant adenovirus harboring the herpes simplex thymidine kinase gene (IG.Ad.MLPI.TK) was injected into the white matter of the right frontal lobe in two rhesus monkeys (M. mulatta). Injection of the vector was followed by systemic ganciclovir administration (10 mg/kg per day) for 14 days. During treatment no clinical symptoms were observed. Histopathological analysis of the brain at day 18 showed a 5 mm necrotic area at the site of the virus injection. This area was invaded and surrounded by inflammatory cells and activated astrocytes (gliosis). Immunohistochemical analysis of the infiltrates revealed the presence of predominantly mononuclear cells. In the vicinity of the lesion perivascular cuffs were seen containing T lymphocytes and clusters of B lymphocytes. From this preclinical study we conclude that the toxicity of adenotk/GCV is acceptable and treatment of patients with malignant gliomas using this kind of therapy is feasible. However, careful dose finding in clinical studies is recommended.

Adenoviridae↗
PubMed1998

Lhermitte's sign following chemotherapy with docetaxel.

Specific causes for Lhermitte's sign (LS) in cancer patients are spinal cord compression, radiation therapy to the spinal cord, and cisplatin chemotherapy. We observed a transient LS in five of 87 patients treated with more than two cycles of 100 mg/m2 docetaxel (Taxotere). LS developed either concurrently or after the onset of docetaxel-induced sensory neuropathy, and disappeared after the discontinuation or dose reduction of chemotherapy.

Adult↗
PubMed1997

[Transdermal opioid administration: the pain plaster].

A new method of administration of an opioid was recently registered: fentanyl transdermal (brand name: Durogesic), intended particularly for the indication range 'pain in cancer'. Fentanyl is lipid-soluble so that deposition in the skin takes place and the biological half-life is approximately 20 hours after removal of the plaster. It is safe to start on a basis of an equianalgesic conversion of 100:1 in relation to oral morphine, although this may entail some risk of fentanyl under dosage. The dose adjustment time is 12-24 hours before a constant fentanyl level is reached; therefore, after attaching the first sticking plaster, the original morphine dose should be continued for another 12 hours. In addition, the patient may, if necessary, be given supplementary morphine preferably as a short-acting drug. There seems to be no clear indication for transdermal fentanyl either in neuropathic pain or in chronic benign pain.

Administration, Cutaneous↗
PubMed1997

99mTc-SPECT in the diagnosis of skull base metastasis.

OBJECTIVE: To evaluate the role of bone SPECT in diagnosing metastasis to the skull base in cancer patients. BACKGROUND: Skull base metastasis often causes characteristic clinical syndromes. Antitumor treatment ameliorates or stabilizes symptoms in most patients. Diagnosis may be difficult when neuroimaging studies are negative (as occurs in about one-quarter of patients). Case reports have suggested a role for bone SPECT in these patients. METHODS: We reviewed the charts of all patients (1993-1996) at our institution who had skull base SPECT and at least one neuroimaging study (CT or MRI) for clinically suspected metastasis to the base of the skull. Bone SPECT, CT, and MRI were blindly re-evaluated. RESULTS: We studied 56 patients, of whom 36 had skull base metastasis. Twenty patients had other causes of the clinical syndrome, including leptomeningeal and posterior fossa metastasis, or benign causes. In 29 of 36 patients (81%) with skull base metastasis, CT or MRI clearly demonstrated the lesion. Bone SPECT identified a hot spot in the appropriate region of the skull base in 28 of 36 patients (78%). All seven patients with negative CT or MRI had positive SPECT and four of these had a response to anti-tumor treatment. CONCLUSIONS: SPECT of the skull base can demonstrate lesions not identifiable by CT or MRI. In cancer patients suspected of having skull base metastasis, we recommend SPECT of the skull base when CT or MRI studies are negative.

Adult↗
PubMed1995

Immunization with the paraneoplastic encephalomyelitis antigen HuD does not cause neurologic disease in mice.

Paraneoplastic encephalomyelitis/paraneoplastic sensory neuronopathy (PEM/PSN) associated with small cell lung cancer is characterized by high serum and CSF titers of anti-neuronal (anti-Hu) antibodies and by intrathecal synthesis of anti-Hu IgG. A pathologic role for the anti-Hu antibodies in PEM/PSN is further suggested by reported intraneuronal accumulation of the antibodies in the nervous system of PEM/PSN patients at autopsy. We immunized SJL/J mice, Lewis rats, and Hartley guinea pigs with purified recombinant HuD fusion protein. In spite of high-titer anti-HuD antibodies, neurologic and pathologic examination of the animals was normal. Apparent uptake of purified IgG by neurons in the brain proved to be artifactual.

Animals↗
PubMed1993

Distribution of metallothionein in the human central nervous system.

The distribution of metallothionein (MT), a metal-binding protein, was examined immunohistochemically in the normal human brain and spinal cord. Paraffin-embedded brain tissue from three patients who had died from a non-neurological disease and were free of histopathological central nervous system alterations were processed. The results of the present study demonstrate that MT is readily detectable in a subgroup of astrocytes in the normal human brain. MT staining is most intense on grey matter astrocytes that bear short stout processes and which probably represent protoplasmic astrocytes. Using anti-MT and anti-glial fibrillary acidic protein immunostaining, we could demonstrate two subpopulations of astrocytes that were mutually exclusive. The functional significance of MT-expression in protoplasmic astrocytes is not entirely clear. Metal detoxification is only one of the many postulated functions of MT. The finding that staining for MT permits subtyping of astrocytes may be of great importance in glia research and surgical pathology of the human brain.

Adult↗