Determinants of vancomycin clearance by continuous venovenous hemofiltration and continuous venovenous hemodialysis

The clearance of vancomycin is significantly reduced in patients with acute, as well as, chronic renal failure. Although multiple-dosage regimen adjustment techniques have been proposed for these patients, there is little quantitative data to guide the individualization of vancomycin therapy in acute renal failure patients who are receiving continuous renal replacement therapy (CRRT). To determine appropriate vancomycin dosing strategies for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies in five stable hemodialysis patients with three hemofilters: an acrylonitrile copolymer 0.6 m2 (AN69), polymethylmethacrylate 2.1 m2 (PMMA), and polysulfone 0.65 m2 (PS). Patients received 500 mg of vancomycin intravenously at least 12 hours before the start of the clearance study. The concentration of vancomycin in multiple plasma and dialysate/ultrafiltrate samples was determined by EMIT (Syva, Palo Alto, CA). The diffusional clearance and sieving coefficient (SC) of vancomycin were compared by a mixed-model repeated-measures analysis of variance (ANOVA) with filter and blood (Q(B)), dialysate inflow (Q(DI)), or ultrafiltration rate (Q(UF)) as the main effects and patient as a random effect. Vancomycin was moderately protein bound in these patients; free fraction ranged from 49% to 83%. The SCs of the three filters were similar and significantly correlated with the free fraction of vancomycin (P = 0.01; r2 = 0.465). Significant linear relationships were observed between the diffusional clearance of vancomycin and Q(DI) for all three filters: AN69 (slope = 0.482; r2 = 0.880); PMMA (slope = 0.853; r2 = 0.966); and PS (slope = 0.658; r2 = 0.887). The slope of this relationship for the PMMA filter was significantly greater than that of the AN69 and PS filters. The clearance of vancomycin, urea, and creatinine, however, was essentially constant at all Q(B)s for all three filters. Thus, the clearance of vancomycin was not membrane dependent during CVVH. However, during CVVHD, membrane dependence of vancomycin clearance was noted at a Q(DI) greater than 16.7 mL/min; vancomycin clearance with PMMA at a Q(DI) of 25 mL/min was 66% and 43% greater than that with the AN69 and PS filters, respectively. CVVH (62% to 262%) and CVVHD (90% to 540%) can significantly augment the clearance of vancomycin in acute renal failure patients. Dosing strategies for individualization of vancomycin therapy in patients receiving CVVH and CVVHD are proposed.     

Diverticular abscesses: percutaneous drainage

Percutaneous catheter drainage was performed in 16 patients with diverticulitis complicated by abscesses. Each patient had resolution of fever within 72 hours. Eleven patients subsequently underwent simultaneous sigmoid resection and operative anastomosis 10-40 days after percutaneous drainage. One patient required a three-stage procedure after percutaneous drainage, and one patient was too unstable for operation at any time during her course and eventually died of respiratory failure. Three patients did not undergo resection after catheter drainage and have remained asymptomatic for 1-2 1/2 years. Ten of 16 patients had fistulas, eight of which closed spontaneously. Experience with percutaneous drainage of diverticular abscesses suggests that it obviates surgical abscess drainage and permits a single operation (sigmoid resection and closure) to be performed safely. Percutaneous abscess drainage has cost-saving implications, since one or two operations may be avoided in most patients, and in some high-risk elderly patients all operations may be obviated.     

Adenosine dialdehyde and nitrous oxide induce HL-60 differentiation

Adenosine dialdehyde and nitrous oxide, specific S-adeno- sylhomocysteine hydrolase and methionine synthetase inhibitors, respectively, induced differentiation of the human promyelocytic cell line HL-60. Their effect did not appear to be mediated through changes in transmethylation or decreased S-adenosylmethionine synthesis because (1) there was little correlation between the concentrations of adenosine dialdehyde that induced differentiation and those that changed the ratio of the intracellular concentrations of S- adenosylmethionine to S-adenosylhomocysteine, and (2) inhibition of methionine adenosyltransferase by cycloleucine did not induce differentiation. The differentiation induced by adenosine dialdehyde was prevented by homocysteine and that by nitrous oxide was inversely related to the medium methionine concentration. This suggested that differentiation was secondary to decreased methionine synthesis.     

Orthotopic cardiac transplantation: evaluation with CT

As cardiac transplantation has become widely available, computed tomography (CT) of the chest has played a useful role in the examination of patients after heart transplantation. To determine anatomic features related to the procedure, the authors evaluated 59 scans in 46 patients who had undergone orthotopic cardiac transplantation. Aortic anastomosis (seen in 98% of scans) and altered spacing between the great vessels (83%) proved to be the most common and most reliable findings. Other features including atrial anastomosis, high main pulmonary artery segment, remnant superior vena cava, and cardiac reorientation were also seen. Accurate interpretation of adenopathy, mediastinal abscess, and pericardial effusion will be enhanced in these patients through a better understanding of the cardiovascular-pericardial complex, which is afforded by CT.     

Cutaneous Rhizopus and Aspergillus infections in five patients with cancer

Primary cutaneous infection with Aspergillus species and Rhizopus species was observed in five patients between October 1986 and January 1988. All patients had an underlying hematological malignancy and were neutropenic. Four patients developed skin lesions with eschars at and around the site of intravenous catheter insertion. One patient had two lesions along the course of the intravenous line. The fifth patient developed the lesion on the left side of the lower part of the back subsequent to the appearance of a rash due to excessive perspiration. A diagnosis was made in each case by histopathological studies and cultures of skin biopsy specimens. The fungal organisms cultured were Aspergillus species in three patients and Rhizopus species in two patients. All patients were treated with amphotericin B. Three patients responded to antifungal therapy and local care without surgical débridgement. Two patients died of disseminated fungal infection. The development of cutaneous lesions due to opportunistic fungal pathogens seemed to have been related to the moist and humid conditions created by occlusive dressings or excessive perspiration.     

Magnetic Resonance Evidence of Perineural Metastasis

Contiguous spread along perineural and endoneural spaces, that is, perineural tumor extension, in cutaneous squamous cell carcinoma is fairly common. Infrequently, these tumors spread and involve intracranial structures. One consequence of th1s complication is meningeal carcinomatosis which is underrecognized. Herein described is a patient with recurrent cutaneous squamous cell carcinoma with perineural invasion along the maxillary nerve that was subsequently shown by magnetic resonance imaging to the trigeminal root The patient Initially presented with a cavernous sinus syndrome but despite aggressive treatment, extensive meningeal carcinomatosis and cauda equina dysfunction developed. Awareness of perineural invasion and proper evaluation are crucial. Penneural spread intracranially worsens the prognosis and limits treatment options to palliation.     

Magnetic resonance imaging of the pelvic floor in the postpartum patient

Magnetic resonance imaging (MRI) was used to assess anatomical changes in the pelvic floor after childbirth. Six women underwent serial MRI examination within 30 hours and at 1 week, 2 weeks, 6 weeks and 6 months after delivery; 8 additional women were studied only within 30 hours of delivery. T-1 and T-2-weighted images of the pelvis in the transverse and sagittal planes with a 1.5-T MR imager were obtained. In the sagittal section we assessed the urethrovesical angle, urethral length, distance from the symphysis to the proximal and distal vagina, vaginal length, width and length of the sphincters, and the presence of sphincter defects. Axial sections were assessed for sphincter defects for the distance between the symphysis and midurethra, vagina and rectum. Only one parameter (distance between symphysis and distal vagina) changed significantly over time, without a clear trend in direction. Interobserver variation was reasonable (<15%) except for anal canal length, urethral length and distance between symphysis and anus. There were no significant correlations between birthweight and MRI parameters. There was a non-significant association (P=0.09) between the sole combined sphincter defect and rectal injury, but not with episiotomy or parity. We concluded that it is feasible to determine multiple measurements on MR images to evaluate structures of the pelvic floor.EDITORIAL COMMENT: Although the presented study has multiple limitations — i.e. small sample size, no control group, static images, lack of correlated symptomatology — the investigators show that magnetic resonance imaging can be used to follow the natural course of pelvic floor changes after vaginal delivery. Hopefully this work will be continued and expanded, shedding more light on the effects of childbirth on pelvic floor anatomy and function.     

Treatment of lymphoid neoplasias with interferon. II. Human leucocyte alpha-interferon in chronic lymphatic leukemia (CLL). PHase I-II trial

Nine patients with chronic lymphoid leukemia (CLL) were treated with subcutaneous human (leukocyte) interferon a (IF a). In the first part of the study, 7 patients received intermittent 10 day courses, with free intervals of 10 to 15 days and with dose escalation in the same patient from cycle to cycle from 1.5 to 6 X 10(6) units daily, if tolerated. As we observed a decrease of peripheral lymphocytosis with low doses, and as high doses gave more side-effect in the second part of the study, 4 patients (including two who has previously received intermittent courses) were treated for three months or more at a dose of 1.5 X 10 units daily. Tumor mass reduction was seen in only three patients. However, a significant decrease in peripheral lymphocytosis was seen in 7 patients who were sustained in the continuous treatment group; with relapse at treatment discontinuation in one patient and despite continuation in another. Immune monitoring with currently available T, B, NK and macrophage tests, showed a good correlation between NK cell activity and clinical response, in this group of patients. Further studies are warranted to determine the best modalities of treatment, the population of patients likely to benefit from such treatment, the possible special respective indications of IF, and also the other treatments of CLL. One can already consider as a reasonable indication CLL presentations with myeloid insufficiency as IF is not myelotoxic, contrary to chemotherapy.