Accidental transmission of HCV and treatment with interferon

Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work-related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunode?ciency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2–3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV-injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.     

In-vitro Characterization of YM872, a Selective,Potent and Highly Water-soluble α-Amino-3-hydroxy-5-methylisoxazole-4-propionate Receptor Antagonist

The in-vitro pharmacological properties of (2,3-dioxo-7-(1H-imidazol-***1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl)-acetic acid monohydrate, YM872, a novel and highly water-soluble α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor antagonist were investigated. YM872 is highly water soluble (83 mg mL^?1 in Britton-Robinson buffer) compared with 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX), 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride (YM90K) or 6-cyano-7-nitroquinoxa-line-2,3-dione (CNQX). YM872 potently inhibits [³H]AMPA binding with a K_i (apparent equilibrium dissociation constant) value of 0.096 ± 0.0024 μM. However, YM872 had very low affinity for other ionotropic glutamate receptors, as measured by competition with [³H]kainate (high-affinity kainate binding site, concentration resulting in half the maximum inhibition (IC50) = 4.6 ± 0.14 μm), [³H]glutamate (N-methyl-D-aspartate (NMDA) receptor glutamate binding site, IC50 > 100 μM) and [³H]glycine (NMDA receptor glycine-binding site, IC50 > 100 μM). YM872 competitively antagonized kainate-induced currents in Xenopus laevis oocytes which express rat AMPA receptors, with a pA₂ value of 6.97 ± 0.01. In rat hippocampal primary cultures, YM872 blocked a 20-μM AMPA-induced increase of intracellular Ca²⁺ concentration with an IC50 value of 0.82 ± 0.031 μM, and blocked 300-μM kainate-induced neurotoxicity with an IC50 value of 1.02 μM. These results show that YM872 is a potent and highly water-soluble AMPA antagonist with great potential for treatment of neurodegenerative disorders such as stroke.     

Interferon-related mental deterioration after craniotomy for removal of metastatic renal cancer

Interferon-related severe adverse events on the central nervous system are relatively rare, because interferon-alpha (INF-alpha) can not cross an intact blood-brain barrier. We experienced remarkable mental deterioration caused by INF-alpha administration in a 43-year-old man with renal cell carcinoma after surgical removal of a metastatic brain tumor. We detected a high concentration of INF-alpha in a cerebrospinal fluid sample, which was comparable to that in the serum at 24 h after the administration of INF-alpha; 5x10(6) IU i.m., suggesting that the blood-brain barrier was damaged somehow by the craniotomy. The mental deterioration improved shortly after discontinuation of the INF-alpha administration.     

Differentiating early and late-onset depression with multichannel near-infrared spectroscopy

Background: Individuals with late‐life depression can be divided into two categories, those with early and late‐onset depression (EOD and LOD, respectively). It has been reported that LOD has more accentuated subcortical vascular lesions and frontal lobe dysfunction (hypofrontality). The aim of the present study was to examine whether LOD exhibits more prominent hypofrontality than EOD during performance of the word fluency task (WFT) under multichannel near‐infrared spectroscopy (NIRS), a newly developed non‐invasive functional neuroimaging technique. Methods: Eleven patients with EOD, 12 patients with LOD, and 13 healthy controls participated in the study. Clinical symptoms of depression were equivalent in the EOD and LOD groups. Brain magnetic resonance imaging demonstrated more robust subcortical vascular changes in LOD than EOD. The NIRS images were obtained using an ETG‐4000, 52‐channel NIRS system (Hitachi Medical, Tokyo, Japan). Mean changes in oxy‐hemoglobin (oxy‐Hb) were evaluated while the participants performed the phonemic WFT. Results: Healthy controls exhibited clear increases in oxy‐Hb bilaterally throughout the medial to the lateral frontal cortices and the superior temporal areas during the WFT. In contrast, increases in oxy‐Hb were mildly attenuated in EOD and severely attenuated in LOD in most channels. Subsequent analyses revealed that increases in oxy‐Hb in LOD during the WFT was significantly poorer than in EOD in the left lateral portion of the cortex, including the dorsolateral prefrontal and the superior temporal areas. In addition, significant negative correlations were obtained between the age of onset and oxy‐Hb, as well as between subcortical vascular changes and oxy‐Hb in the lateral channels. These findings suggest that the higher the age of onset of depression, and the more prominent the vascular lesions, the greater the attenuation in lateral frontal and temporal activation, as indicated by NIRS. Conclusions: Multichannel NIRS is useful for demonstrating attenuated functional activation in the left lateral prefrontal and temporal areas in LOD and, thus, for differentiating between LOD and EOD. The NIRS findings observed may have useful clinical implications for treatment‐resistant LOD.     

Treatment of Malignant Tumor in the Head and Neck: --Interdisciplinary Collaboration of Surgery and Radiotherapy--

Although the prime importance in treatment of head and neckcancer is eradication of tumors, due attention should be paidto the conservation of many important structures and functionsin the region. Just to mention a few of these important humanfunctions, there are phonation, digestion and facial expression.Simple surgical procedures specialized by otolaryngologistsare no longer satisfactory. Recently, radiotherapy of head and neck cancer has developedto a superlative degree and chemotherapy to a practical degreealthough much still remains to be satisfied. Our aim was toorganize an interdisciplinary group of specialists in surgery,radiotherapy and regional chemotherapy into a composite attackforce. We aimed at most effective treatment with the least ofside effects. Since 1961, our combined approach to cancer of the head andneck in close collaboration with radiotherapists has yieldedmuch improved results. This has led to an increasing numberof patients with satisfactory rehabilitation.

1. 1. Cancer of the maxilla: Even in the advanced cases combinedsurgery, radiotherapy and regional chemotherapy has led to thepreservation of important structures and functions. Many patientsare now allowed to return to social life and to their previousjobs.
2. 2. Cancer of the nasopharynx: Radiotherapy is the firstchoice.When the effect is less satisfactory, chemotherapy anda window-operationof the palate are performed.
3. 3. Tumorsof the tonsils: The majority of patients suffer fromthe reticulumcell sarcoma. Radiotherapy is the first choice.
4. 4. Cancerof the larynx: A full dose of radiotherapy is thefirst choice.Partial resections are done when indicated.
5. 5. Cancer of thetongue, hypopharynx and esophagus: Radiotherapyis the firstchoice in the majority of cases. Some need plasticsurgery.

     

Malignant transformation of renal angiomyolipoma

In the present paper, two cases of malignant transformation of renal angiomyolipoma without tuberous sclerosis are reported. Pathological examination revealed that, in both cases, in addition to the areas affected by typical angiomyolipoma, there were areas that contained elevated numbers of perivascular epithelioid cells with prominent nuclear pleomorphism. Immunohistochemical examination revealed that both cases were negative for keratin and epithelial membrane antigen, but were positive for the melanogenesis-related marker HMB-45. Metastatic diseases appeared 40 months after radical nephrectomy in the first case and 18 months in the second case.     

RESPIRATORY FUNCTION DURING CERVICAL AND THORACIC EXTRADURAL ANALGESIA IN PATIENTS WITH NORMAL LUNGS

Lung volumes, expired gas volumes, tests of ventilatory capacityand blood-gas tensions were measured in women before and afterinduction of cervical or thoracic extradural analgesia using2% mepivacaine. Inspiratory capacity, vital capacity, totallung capacity and FEV₁, all decreased significantly 30 min afterboth cervical and thoracic extradural blocks. The changes observedduring cervical block were significantly greater than thoseobserved during thoracic extradural analgesia. Expiratory reservevolume and functional residual capacity decreased significantlyafter thoracic cxtradural block, but did not change after cervicalextradural block. Reduction in expired minute volume was observedin the two groups. Pa_co2 and alveolar-arterial oxygen tensiondifference increased, and Pa_co2 decreased significantly 25 minafter both blocks. These results demonstrate that pulmonaryventilation is slightly impaired by the two blocks and to thesame degree, but ventilatory reserve and capacity are markedlyimpaired by cervical extradural block. ^* Present address: Department of Anesthesiology, Shimane MedicalCollege and Hospital, Izumo City, Shimane-Ken, Japan.