Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy

Background: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.

Methods: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg [middle dot] kg-1 [middle dot] h-1 [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.

Results: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).     

Cytochrome P-45011 beta in rat brain

The presence of cytochrome P-45011 beta in rat brain was studied by immunohistochemistry using polyclonal rabbit antibodies raised against purified bovine adrenocortical P-45011 beta, which is involved in the steroid 11 beta-hydroxylation and glucocorticoid formation. The results showed that cytochrome P-45011 beta immunoreactivity is selectively localized to the tracts of myelinated fibers throughout the brain. The specificity of immunohistochemical stainings with P-45011 beta antibodies was established by control tests including nonimmune rabbit immunoglobulin Gs and P-45011 beta antibodies absorbed with purified antigen. Western immunoblots of homogenates from different brain areas with P-45011 beta antibodies, together with biochemical enzymatic assays for cytochrome P-45011 beta monooxygenase activity in these homogenates, confirmed the selective localization of this enzyme observed with immunohistochemistry. Cytochrome P-45011 beta and 11 beta-hydroxylase activity were detected in a homogenate from the cortical white matter (brain area rich in myelinated fibers) as in that from the rat adrenal, but were not detectable in a homogenate from the cerebral cortex (brain area poor in myelinated fibers). Furthermore, quantitation of the P-45011 beta bands on the immunoblots by the areal density revealed that the cortical white matter contains approximately 1.4 pmol of cytochrome P-45011 beta/mg of tissue protein, the value of which was about one sixth of the corresponding value estimated in the rat adrenal. This relatively high content of cytochrome P-45011 beta was also reflected in a relatively high level of 11 beta-hydroxylase activity measured in a homogenate of this brain area by biochemical enzymatic assays using [4-14C]-11-deoxycorticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful treatment with balloon dilatation using a double‐balloon enteroscope for a stricture in the small bowel of a patient with Crohn's disease

The requirement for endoscopic access to a stricture is a major limitation of the endoscopic dilatation for the treatment of strictures in the gastrointestinal tract. We have developed the double‐balloon enteroscopy method that enables visualization of the entire small bowel. In addition, double‐balloon enteroscopy has a potential for the interventional therapy including dilatation of strictures. We present here a case of jejunal strictures in a 47‐year‐old woman with Crohn's disease successfully treated with a balloon catheter in combination with double‐balloon enteroscopy. Balloon dilation with double‐balloon enteroscopy is a promising method for the treatment of small bowel strictures in Crohn's disease.     

Endogenous inhibitory system in pain

Electrical stimulation of several brain sites produces profound analgesia in humans, and inhibits nocifensor reflexes in animal studies. Responses of the dorsal horn nociceptive neurons evoked by stimulation onto the receptive fields are also inhibited by brain stimulation. These brain sites are Periaqueductal Gray Matter (PAG), Nucleus Raphe Magnus (NRM), Nucleus Reticularis magnocellularis (NRmc), Locus Coeruleus (LC), Lateral Hypothalamus, and others. We have explained in a general way the mechanism of these stimulation produced analgesia. The mechanism of PAG stimulation analgesia is partly due to an activation of serotonin containing neurons which descend from NRM to the spinal dorsal horn and activated by PAG stimulation. Activation of NRM neurons may produce inhibition of the nociceptive neurons of the dorsal horn by the mechanism of direct postsynaptic inhibition. Currently there is no evidence to support the theory of presynaptic inhibition. Endogenous opioid peptides do not play an important role in PAG stimulation analgesia. On the other hand, the mechanism of NRmc or LC stimulation analgesia may be due to an activation of noradrenaline containing neurons which similarly inhibit the dorsal horn nociceptive neurons in the spinal cord. At present, it still remains unknown whether endogenous opioid peptides play an important role in this type of analgesia.     

Evaluating New and Traditional Methods for Aminoglycoside Dosing in Patients With Various Degrees of Renal Function

Aminoglycosides are widely used, and clinicians continue to seek newer and better methods for initial dosing of these agents. Recently, three new methods were introduced: Thomson, Reesor Nimmo, and dosing in Tenopathy by easy-to-use multipliers (DREM). In comparing them with older, traditional dosing methods in patients with various degrees of renal function, the pharmacokinetic variables of gentamicin were determined from steady-state peak (C_max) and trough (C_min) serum concentrations using individualized regimens in 88 patients. Dosages were determined in each patient using the method of Hull-Sarubbi, rule of eights, and the three new methods, and the resultant C_max and C_min values were calculated from dosages generated by each method. The daily doses and C_max values derived with the Hull-Sarubbi, Thomson, and Reesor Nimmo methods were not significantly different (p>0.05). The Hull-Sarubbi was the most precise (root mean squared prediction error 1.3) and least biased (mean prediction error −0.05) of the five methods in predicting target gentamicin serum peak concentrations (C_max 6.5 mg/L). The Hull-Sarubbi (69%), Thomson (86%), and Reesor Nimmo (70%) methods yielded therapeutic C_max (5–8 mg/L) in a significantly higher percentage of patients than did the rule of eights (32%) and DREM (35%), (p<0.05). Therefore, if gentamicin serum concentrations are not available, the first three appear to be reasonable methods for initiating gentamicin dosage regimens, but the last two may not be desirable to use in a clinical setting. These conclusions are based on the assumption that patients are adults with stable renal function and relatively stable clinical conditions.     

Kimura's disease associated with minimal change nephrotic syndrome: A case report

Kimura's disease is a rare disorder that involves regional lymph nodes and the major salivary glands, which become infiltrated by eosinophils and lymphocytes. Renal lesions associated with Kimura's disease are rare. We describe the case of a 60-year-old Japanese woman who first noted a nodular mass in a salivary gland. As the nodule grew, nephrotic syndrome and heart failure developed. A biopsy of the nodule revealed Kimura's disease, and surgical excision was performed. After the operation, the heart failure and nephrotic syndrome, which were diagnosed as minimal change disease on renal biopsy, improved rapidly without steroid therapy. Four months later, the nephrotic syndrome recurred without recurrence of Kimura's disease. The patient showed marked improvement during prednisolone therapy (40 mg/d) and was in complete remission 4 weeks after the initiation of steroid therapy. This case shows that surgical excision and prednisolone therapy are useful for nephrotic syndrome associated with Kimura's disease.     

Seborrhoeic Dermatitis: Treatment with Anti-Mycotic Agents

In order to elucidate the effectiveness of anti-mycotics in treating seborrhoeic dermatitis, an attempt was made to isolate Malassezia from seborrhoeic lesions of patients of seborrhoeic dermatitis. The results revealed that, in male patients, 46/49 cases were positive for Malassezia furfur on the face and 30/48 cases were positive for M. furfur on the scalp. In female patients, 7/13 cases were positive for M. furfur on the face, and 6/17 cases were positive for M. furfur on the scalp. Anti-mycotic agents were excellent in 50% and good in 31% of the spore-positive cases, yielding an overall efficacy rate of 81%. In contrast, the treatment of the face with vehicle alone showed only one excellent result out of 8 cases. Although clinical improvement was rapid on the side treated with a topical corticosteroid in the half-side-test, numerous fungal elements remained. While the improvement with anti-mycotic agents was slower than that with the corticosteroid, clinical improvement became evident by the third week of administration and fungal elements disappeared.     

The efficacy of fluconazole in treating prosthetic valve endocarditis caused byCandida glabrata: Report of a case

A case of active prosthetic valve infective endocarditis (PVE) due toCandida glabrata was successfully treated by the systemic administration of fluconazole. A 66-year-old Japanese man with infective endocarditis of unknown etiology underwent aortic and mitral valve replacement to treat severe aortic and mitral regurgitation associated with multiple organ failure. Postsurgical cultures of arterial blood were repeatedly positive forC. glabrata, and therefore fluconazole was administered either intravenously or orally at a dose of 400 mg/day for 46 days. During that time the signs of inflammation including fever such as an elevated white blood cell count and the presence of C-reactive protein (CRP) all improved while the blood cultures became negative. Fluconazole is thus considered to be effective in treating PVE caused byC. glabrata. When administering this treatment, it is also important to monitor the patient's renal and liver function.     

Phase II study of etoposide (VP-16) in the form of intravenous injection for malignant lymphomas and acute leukemias: Hanshin Cooperative Study Group for Hematological Disorders

Twenty patients with malignant lymphomas and 12 with acute leukemias were treated with intravenous administration of etoposide, 60-100 mg/m2/day for five days, repeated for three to four weeks. Eighteen cases of malignant lymphoma and nine of acute leukemia were evaluable. CR was achieved in three cases (16.7%) and PR in four cases (22.2%) of malignant lymphoma. Although CR was not achieved in any patients with acute leukemia, and PR was in three (33.3%), it was found that etoposide was most effective for the patients with the M4 or M5 subtype in the FAB classification. The most serious adverse effect of the drug was leukopenia in patients with lymphoma. In three patients (30.0%), the leukocyte count was lower than 1,000/mm3. Gastrointestinal complications, such as anorexia, nausea, vomiting and diarrhea occurred in 60.7% of all patients, but were not serious. Alopecia was observed in 73.1%. Intravenous administration of etoposide was apparently effective for the patients with malignant lymphoma of the diffuse mixed type, and this efficacy found in our study was the same as that for oral administration of etoposide reported by us previously.