Answers to Self-Assessment examination of the American Academy of Dermatology.
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Journal Article↗
Biomedical subjects
T Kahn
Publications and source records attributed to T Kahn.
Hyperthermia for the treatment of patients with malignant germ cell tumors: a phase I/II study in ten children and adolescents with recurrent or refractory tumors.
BACKGROUND: Extracranial nontesticular germ cell tumors (GCTs) are rare malignancies in children and adolescents. Cisplatin-containing regimens and complete tumor resection are important determinants for a favorable outcome; however, patients with recurrent tumors that cannot be eradicated by surgical procedures and chemotherapy have a poor prognosis. Noninvasive electromagnetic technologies for superficial and regional deep hyperthermia (RHT) are under investigation to enhance local tumor control in various malignancies. The objectives of this Phase I/II study were to examine 1) whether RHT can be used in combination with platinum-based chemotherapy with acceptable toxicity in children and adolescents and 2) whether this combined regimen can induce objective tumor response in patients with malignant nontesticular GCT that persisted or recurred locoregionally after validated, intensive, cisplatin-based chemotherapy +/- surgery as unsuccessful first-line treatment. METHODS: The authors studied the effects of RHT induced by electromagnetic waves in combination with platinum-based chemotherapy in ten children and adolescents with recurrent or refractory GCTs. RESULTS: Seven of ten patients with recurrent or refractory GCTs had objective responses. Of these, two patients had a partial response and five patients had a complete response. CONCLUSIONS: The results of the current study found that combined RHT and platinum-based chemotherapy can be used in children and adolescents. This regimen was found to induce objective tumor response in 70% of study patients with recurrent or refractory GCTs. The results thus far are encouraging and the study has been extended to patients with a poor response to first-line treatment.
Adolescent↗
APM-1, a novel human gene, identified by aberrant co-transcription with papillomavirus oncogenes in a cervical carcinoma cell line, encodes a BTB/POZ-zinc finger protein with growth inhibitory activity.
Integration of human papillomavirus (HPV) DNA into the host cell genome is an important step in cervical carcinogenesis. In tumour cells with integrated HPV DNA, transcription of viral oncogenes E6 and E7 continues into the flanking cellular sequences thereby producing viral-cellular fusion transcripts. Analysis of cellular sequences flanking the integrated HPV68 DNA in the cervical carcinoma cell line ME180 revealed homozygosity of the mutant allele in ME180 cells. We speculated that this could indicate the existence of a cellular tumour suppressor gene in the integration region. We report here the identification of a novel human gene, named APM-1, which is co-transcribed with the HPV68 E6 and E7 genes and is present in the 3'-cellular part of the ME180 viral-cellular fusion transcripts. The APM-1 gene encodes a protein with a BTB/POZ domain and four zinc fingers, and is located at chromosome 18q21. APM-1 transcripts are detected in normal cervical keratinocytes, but not in the majority of cervical carcinoma cell lines analysed. The APM-1 gene caused a reduction of clonal cell growth in vitro of HeLa and CaSki tumour cells. These characteristics make APM-1, the first novel human gene identified in a HPV integration region, a likely candidate for the postulated tumour suppressor gene.
Alleles↗
Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control.
Two hundred eight primary squamous cell carcinomas of the head and neck have been analyzed with respect to the presence of the retinoblastoma tumor suppressor protein, pRb. Of these, 23 tumors (11%) that preferentially localized to the tonsils revealed complete absence or dramatic reduction in the amount of pRb. Other cell cycle components, cyclin D1 and p16INK4A, which are intimately related to pRb through an autoregulatory loop, were also dramatically decreased or overexpressed, respectively, in these pRb-defective tumors. On the other hand, the majority of the pRb-defective tumors contained the wild-type p53 gene. No evidence was found for genetic defects at the Rb locus in these tumors. Very significantly, in 11 of 12 pRb-defective tonsillar tumors, but in none of 9 pRb-positive tonsillar tumors (P < 10[-7]), DNA of oncogenic human papillomavirus types was identified, providing a strong indication for a human papillomavirus-associated etiology of these tumors and suggesting the functional inactivation of the pRb protein by the viral E7 gene product. In comparison to all head and neck squamous cell carcinomas studied, the pRb-defective tonsillar tumors were in general more poorly differentiated (P = 0.0059), and they were all metastatic at the time of resection. Of particular clinical interest, despite these adverse histopathological factors, the clinical outcome for these patients was relatively favorable, strongly implying that the pRb-defective tumors responded uniformly well toward postoperative radiation therapy.
Carcinoma, Squamous Cell↗
Induction of a CD3+/CD56+ lymphocyte population following gene therapy with transgenic IL-2 secreting fibroblasts in a child with peripheral neuroectodermal malignancy.
BACKGROUND: Adjuvant interleukin-2 (IL-2) therapy after stem cell transplantation can improve the prognosis of patients with Ewing tumors. This has been attributed to stimulation of the immune system and its antineoplastic activity, thus eliminating minimal residual disease. As the side effects of systemic IL-2 limit the dosage, attempts have been made to locally augment the concentration of IL-2 in the proximity of the tumor. To achieve this, fibroblasts and/or tumor cells can be genetically modified to secrete IL-2 and then be injected to generate tumor immunogen. PROCEDURE: In a preliminary clinical trial we assessed whether the administration of transgenic IL-2-secreting fibroblasts was feasible without major toxicity and whether it had any effect regarding the activation of the immune system. We treated an 11-year-old boy with a peripheral neuroectodermal tumor of the left neck in fourth relapse, who was refractory to all available therapy. We transfected fibroblasts of the patient with an IL-2 gene expression vector using a cationic liposome reagent. In 51Cr cytotoxicity assays we obtained lysis of this patient's tumor cells by IL-2-stimulated mononuclear cells (MNCs). Under CT-guidance we intratumorally injected IL-2 transgenic autologous fibroblasts. RESULTS: We observed no local or systemic toxicity. In addition, we found a rise in the CD3+CD56+ lymphocyte population, previously described as cytokine-induced killer cells. No other hematological parameter changed significantly. CONCLUSIONS: Our data suggest that the intratumoral injection of transgenic IL-2-secreting fibroblasts is feasible without major toxicity and may lead to an increase in CD3+CD56+ cells.
CD3 Complex↗
[Interventional MR tomography. Current status and future perspectives].
The concept of MR guidance of invasive diagnostic and minimally invasive therapeutic procedures is based on the excellent morphologic and functional properties of MR imaging. Prerequisites are adequate patient monitoring and adherence to safety guidelines. Fast and ultrafast sequences, temperature quantification, visualization of intravascular devices, thermal stability of contrast media and thermosensitive contrast media are discussed. The spectrum of clinical applications includes biopsies, thermal ablation modalities, vascular applications, MR endoscopy and intraoperative MR imaging. The development of interventional MR imaging is still in its infancy. In the future, MR imaging may play an important role in interventional radiology and minimally invasive therapy.
Biopsy↗
Control of renal factors in plasma homovanillic acid measurements.
To identify and control renal factors affecting plasma homovanillic acid (HVA), a dopamine metabolite and an indicator of brain dopamine activity in clinical research, nine healthy subjects were studied on 5 nonconsecutive days. First study day was the baseline and on the other days base, salt, water, or probenecid loads were given. On each day serial concentrations of HVA and serotonin metabolite 5-hyroxyindoleacetic acid (HIAA), another organic anion, in plasma were measured. Results suggested that base, salt, and water loads did not affect plasma concentrations of either metabolite. Probenecid, which partially blocks renal organic anion transport, induced similar increases in plasma HVA and HIAA. When plasma HVA:HIAA ratio was used to control for the effect of probenecid, differences between baseline and probenecid days were no longer significant. Results suggest that HVA and HIAA are similarly handled by the kidney and that simultaneously measured plasma HIAA could be used to distinguish renal influences in plasma HVA studies.
Adult↗
Prevalence of human papillomavirus in squamous cell carcinoma of the head and neck determined by polymerase chain reaction and Southern blot hybridization: proposal for optimized diagnostic requirements.
Human papillomaviruses (HPV) are discussed as cofactors in the carcinogenesis of squamous cell carcinoma of the head and neck (SCCHN). The prevalence of HPV infection in SCCHN is the subject of controversy since reported HPV prevalences range from less than 10% to almost 100%, depending mainly on the detection method employed. This study presents a realistic approximation to the real prevalence of HPV in SSCHN by applying polymerase chain reaction (PCR) and Southern blot hybridization (SBH), which are the most sensitive and specific HPV detection methods. Diagnostic procedures were optimized by applying a "hot-start" PCR protocol followed by a confirmatory SBH of the PCR products to reactions using both type-specific and consensus primers and probes. DNA of 75 tumour samples and 22 normal mucosa samples of the same patients were investigated. In 14 cases genomic SBH using complete HPV genomes as probes was performed additionally. HPV DNA was detected in 17/75 (22.7%) SCCHN specimens. HPV 16 was identified in four cases, HPV 45 in three cases, and HPV 6 and 18 in one case each. Hot-start PCR and SBH are the most reliable HPV detection methods, as they minimize both false-positive and false-negative results. With these methods, a HPV prevalence of 23% was achieved, which can be assumed to be representative for comparable study populations. The significant number of positives detected only by consensus primer PCR, along with the identification of HPV 45, indicate that further HPV types may play an important role in the genesis of SCCHN.
Adult↗
Idiopathic partial thrombosis of the corpus cavernosum.
A case of spontaneous, partial, unilateral thrombosis of the corpus cavernosum is described. A 35-year-old white male presented with a painful mass in the perineum without priapism. Diagnostic evaluation with sonography and magnetic resonance imaging revealed a thrombosis in the left posterior corporal body. Treatment consisted of intravenous heparin followed by prophylactic acetylsalicylic acid. The thrombosis resolved spontaneously over several months without sequelae. Conservative management of this rare disease appears to be possible and safe.
Adult↗
Diurnal variation in plasma homovanillic acid: not a renal phenomenon.
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Adult↗
Determination of laser-induced temperature distributions using echo-shifted TurboFLASH.
An echo-shifted TurboFLASH sequence implemented on a clinical whole body MR scanner was used to determine thermal changes in tissue. With this snapshot-like data acquisition, temperature-related phase shifts were measured with a temporal resolution of 1.3 s. For different types of tissue (postmortem porcine brain, liver, and muscle) the temperature coefficients of the proton chemical shift were recorded during uniform heating of the specimen in a water bath. The specific temperature-dependent frequency shifts appeared similar to the proton chemical shift of free water (-0.01 ppm/degrees C). With this method, laser-induced ablation in postmortem porcine brain was monitored by temperature mapping. Comparison of the induced temperature profiles measured with NiCrNi-thermocouples with the MR calculated profiles demonstrated excellent temperature sensitivity and accuracy for this method of MR thermometry, with a maximum deviation of the determined temperatures of only 1.8 degrees C. This investigation was designed as a feasibility study for this rapid version of the phase mapping method, and no in vivo studies were performed.
Animals↗
The value of new MRI techniques in adrenoleukodystrophy.
PURPOSE: To evaluate the significance of new techniques in MRI examinations of the brain in children with X-linked adrenoleukodystrophy (ALD). MATERIALS AND METHODS: Five patients aged between 2 and 15 years with childhood ALD were examined with MRI. Following conventional spin-echo (CSE) sequence, a fast spin-echo (FSE) sequence with T2 contrast was performed in four patients, an FSE turbo-inversion-recovery (TIR) sequence in two, magnetization transfer contrast (MTC) imaging in two, and localized proton spectroscopy (MRS) in four patients. RESULTS: FSE compared favorably with CSE with a time saving of 70%. On TIR images the contrast between normal and demyelinated white matter was greater than on CSE and FSE images. Calculated MTC values revealed a severe MTC loss within the demyelinated regions and a moderate reduction in the border zones. In this way, calculation of MTC might be useful to differentiate between edematous changes and areas of irreversible demyelination. MRS revealed a reduction in N-acetylaspartate and an elevation in choline (Cho). The degree of MRS changes paralleled the severity of demyelination. A Cho elevation may precede visible demyelination on T2-weighted images. CONCLUSIONS: T2-weighted FSE sequences can replace CSE without any disadvantages and with effective time saving. The indication for MTC imaging and MRS in children with ALD is not yet finally defined. These new techniques may reveal the earliest signs of cerebral involvement or of disease progression, a matter of great importance in selecting the optimal therapeutic approach.
Adolescent↗
[MR tomographic temperature quantification at 1.5 T in vitro: a comparison of fast T1 maps and a phase-sensitive sequence].
PURPOSE: To determine the value of fast T1-maps and a phase-sensitive sequence for temperature quantification with MR imaging. MATERIAL AND METHODS: The experimental setup allowed both homogeneous heating as well as laser-induced interstitial thermotherapy (Nd:YAG, 1064 nm) of tissue specimens (pig brain, liver and muscle) in vitro. A total of 60 experiments were performed. T1-maps were calculated by means of a multi-point-turbo-FLASH sequence. Additionally, the temperature dependent phase shift was determined with a 2D-FLASH sequence. RESULTS: The T1-relaxation times of four different aqueous solutions of gadolinium-DTPA (0.125-1.0 mmol/l) varied by less than 5%. During homogeneous heating, the T1-maps revealed a linear correlation (r > 0.98) between temperature and T1-relaxation times. The temperature coefficients were 11.0 +/- 0.42 ms/degree C. Variations of the linear correlation were observed during laser irradiation. There was only slight variation of the temperature coefficients of the chemical shift during homogeneous heating of different tissues (brain: 0.0098 +/- 0.0002 ppm/degree C; muscle: 0.0109 +/- 0.0003 ppm/degree C; liver: 0.0093 +/- 0.0002 ppm/degree C). The temperatures calculated during laser therapy based on the phase shift correlated strongly (r = 0.99) to the measured temperatures. CONCLUSION: Due to the considerable tissue independence and high accuracy, the phase mapping method is superior to T1-maps for monitoring thermal therapy modalities at 1.5 T in vitro.
Animals↗
Low-risk human papillomavirus types 6 and 11 associated with carcinomas of the genital and upper aero-digestive tract.
BACKGROUND: Human papillomavirus (HPVs) types 6 and 11, are frequently found in non-malignant anogenital condylomas and laryngeal papillomas. However, in an ongoing epidemiological study in Argentina in which 163 anogenital and aero-respiratory cancer biopsies were analyzed, several cases infected with low-risk HPVs could be detected. METHODS: Tumor samples were analyzed by Southern blot hybridization, using HPVs 6, 11, 16, 18, 30, 31, 33 and 35 as probes, and polymerase chain reaction (PCR) with type-specific primers and probes. RESULTS: Four invasive carcinomas containing HPV 6 or 11 could be detected (2.4%) by Southern blot technique. HPV 6 DNA was found in a penile carcinoma, a groin carcinoma, and in a tonsillar carcinoma. One cervical carcinoma harbored HPV 11 DNA. Using HPVs 6, 11, 16, 18 and 33 anticontamination primers and probes in PCR, no additional high-risk HPV types could be detected in these four cancers. CONCLUSION: This report shows the presence of low-risk HPVs (HPV 6 and 11) associated to malignant tumors in a frequency higher than usually observed. The data raise questions about which are the circumstances which may favor low-risk HPV related oncogenesis.
Blotting, Southern↗
Diffuse polymicrogyria associated with an unusual pattern of multiple congenital anomalies including turribrachycephaly and hypogenitalism.
A newborn male infant born to consanguineous parents was found to have diffuse polymicrogyria associated with an unusual pattern of congenital anomalies including microbrachycephaly, turricephaly, blepharophimosis, microstomia with maxillary retrusion and mandibular prognathism, micropenis with cryptorchidism, camptodactyly and adducted thumbs, and a progeroid appearance. The combination of manifestations in our patient represents a unique form of polymicrogyria with congenital anomalies, probably representing a new syndrome.
Abnormalities, Multiple↗
Fast spin-echo MR imaging of the pediatric brain.
On a 1.5-T MR unit conventional spin-echo (CSE) and fast spin-echo (FSE) images were obtained in 70 consecutive children ranging from 4 days to 13 years in age. They suffered from developmental retardation, neurodegenerative, ischemic or inflammatory diseases. In our prospective study artifacts, lesion conspicuity and general impression were compared between double-echo (proton density- and T2-weighted) CSE and single-echo (T2-weighted) FSE images. Phase artifacts from flowing blood were seen rarely on the FSE images, while motion artifacts appeared more frequently. Assessment of myelination in 43 children with unfinished myelination revealed no difference between FSE and CSE. The lesion conspicuity in 20 children with focal abnormalities compared favorably between FSE and CSE. There was no diagnostically relevant difference between FSE and CSE, although in FSE spin density images were missing. FSE sequences can be used in MR imaging of the pediatric brain without disadvantage and with a time reduction of 67-75%.
Artifacts↗
Congenital muscular dystrophy with laminin alpha 2 chain deficiency: identification of a new intermediate phenotype and correlation of clinical findings to muscle immunohistochemistry.
UNLABELLED: The laminins comprise of a family of heterotrimeric proteins of the extracellular matrix. The crossshaped proteins consist of a heavy alpha-chain and two light chains, called beta and gamma. Each group of chains, classified on their sequence identity and domain organization, include different isoforms. A deficiency of the alpha 2 chain of laminin-2, previously termed merosin or M component, was shown to be responsible for one form of congenital muscular dystrophy (CMD). We investigated muscle biopsies of 20 patients with the clinical diagnosis of CMD and histological evidence of muscular dystrophy for the expression of different laminin chains. Patients with evidence of pachygyria/lissencephaly of the CNS were excluded from this series. The immunohistochemical analysis was correlated to clinical findings and MRI data of the brain. Of 20 patients, 11 (55%) revealed complete or near-complete deficiency of the alpha 2 chain in their skeletal muscle specimens. So far none of these patients became ambulant. Of 20 patients 2 showed partial but clear-cut alpha 2 chain-deficiency. These two patients became ambulant at 18 months and 3 years. All 13 patients with complete or partial alpha 2 chain-deficiency demonstrated cerebral white matter changes on MRI. In contrast, 6/7 CMD patients with normal alpha 2 chain expression became ambulant and none of the 6/7 tested showed evidence of cerebral abnormal T2 sequence signal of the myelin on MRI. CONCLUSION: Our findings emphasize the use of immunohistochemistry for laminin alpha 2 as a diagnostic tool in defining CMD and characterize a milder phenotype with partial alpha 2 chain-deficiency.
Adolescent↗
[Laser-induced interstitial induced hyperthermia of cerebral tumors with nuclear magnetic resonance tomography control].
PURPOSE: The purpose of our study was to determine the value of MRI in monitoring laser-induced interstitial thermotherapy (LITT) of cerebral neoplasms. MATERIALS AND METHODS: Sixteen patients with brain tumors were treated with LITT. The laser irradiation was performed within the MR unit and monitored with a temperature-sensitive T1-weighted 2D-FLASH sequence. RESULTS: During irradiation a gradually increasing central zone of high signal intensity was surrounded by an increasing area of reduced signal intensity. After therapy, the diameter of an enhancing rim at the outer border of the peripheral zone indicated total lesion size. On T2-weighted images the signal intensities were reversed. Total lesion size decreased during follow-up. CONCLUSION: MRI is suitable for monitoring LITT. However, the role of LITT in the treatment of brain tumors has still to be defined.
Adult↗