Potentiation of antifungal activity of amphotericin B by azithromycin against Aspergillus species

The potential role of azithromycin in combination with amphotericin B against 25 clinical isolates of Aspergillus was assessed. The MIC of amphotericin B was 1 microg/ml for 44% of the isolates, 0.5 microg/ml for 48%, and 0.25 microg/ml for 8%. All isolates were resistant to azithromycin. Synergism, defined as a > or = twofold reduction in the MIC of both drugs upon combination, was demonstrated between amphotericin B and azithromycin for all 25 isolates. To prove that azithromycin exerts its antifungal effect by inhibiting protein synthesis, we studied [35S]-methionine incorporation into protein in one Aspergillus isolate. Neither amphotericin B at 0.125 microg/ml (fourfold below its MIC) nor azithromycin at 16 microg/ml (> or = 16-fold below its MIC) had any effect on protein synthesis when tested alone. Upon combination, however, a 68% inhibition in protein synthesis was evident by the inhibition of [35S]-methionine incorporation.     

Favorable results of implantable cardioverter-defibrillator implantation in patients older than 70 years

BACKGROUND: The clinical results of implantable cardioverter-defibrillator (ICD) implantation in the elderly have received limited documentation. As the longevity of the U.S. population has increased, so has the need for ICD implantation in the elderly. We evaluated the efficacy and outcome of ICD implantation in elderly patients (>70 years) compared with younger patients. METHODS: The case records of all consecutive patients who underwent ICD implantation at our institution between 1986 and 1994 were reviewed. Of a total of 238 patients, 78 patients were 70 years of age or older and 160 patients were younger than 70 years of age. RESULTS: The mean age of the younger group was 58 years and that of the elderly group was 74 years. There were no statistical differences in the presence of coronary artery disease, left ventricular systolic function, the inducibility of arrhythmias, or the history of sudden cardiac death. The hospital morbidity rate was similar in both groups (6.9% in the younger group and 7.7% in the elderly group; p = not significant). The operative mortality rate was 1.9% for the younger group and 1.3% for the elderly group (p = not significant). At a mean follow-up of 33 +/- 26 months, Kaplan-Meier survival curves demonstrated similar survival rates, with 93%, 82%, and 65% of the patients alive at 1, 3, and 6 years, respectively. CONCLUSIONS: Implantable cardioverter-defibrillator implantation was equally effective in the treatment of patients older than 70 years as in younger patients. No differences in theoretic survival or morbidity were observed.     

Genomic diversity among Streptococcus agalactiae isolates detected by a degenerate oligonucleotide-primed amplification assay

A random-amplified polymorphic DNA assay using partially degenerate oligonucleotides as primers was used for the characterization of 78 epidemiologically related and unrelated clinical isolates of Streptococcus agalactiae belonging to different serotypes. Thirty distinct amplification profiles were obtained among 52 unrelated S. agalactiae isolates assigned to nine groups by serotyping (including 3 nontypeable strains), uncovering the extent of genomic heterogeneity existent within serotypes. This method was particularly useful in providing evidence for or against vertical transmission of a given clone of this microorganism, as well as for relapsing or reinfection in related cases, and suggested clonal relatedness between unrelated S. agalactiae isolates associated with some invasive infections. Thus, this simple methodology represents a suitable tool for the epidemiologic study of S. agalactiae infections.     

Chromosomal localization of the human and mouse hyaluronan synthase genes

We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17.HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome.     

Hepatitis-B virus and schistosomiasis infections in childhood proteinuria

Hepatitis-B surface antigen (HBsAg), circulating anti-schistosomal IgG (CSAb) and circulating specific schistosomal immune complexes (CIC) were detected, using ELISA, in sera of 40 active nephrotic children, 40 active S. mansoni infected cases and 20 apparently normal age-matched controls. The presence of HBsAg cases was significantly higher among nephrotic cases (20%), active S. mansoni cases (17.5%) than controls. Moreover, HBsAg cases were significantly higher in positive CIC S. mansoni cases than negative CIC ones. The mean O.D. readings of CSAb was significantly higher in positive HBsAg nephrotic cases than negatives. At the same time, the anti-schistosomal antibodies were higher in S. mansoni cases with proteinuria than those without. Specific CIC level was significantly higher among nephrotic and schistosomiasis cases than controls. The CIC were significantly higher in schistosomiasis cases with positive HBsAg than those with negative HBsAg and were detected in 80% of cases with proteinuria compared to 37% of cases without proteinuria with a statistically significant difference. On the other hand, CIC level was not influenced, in nephrotic cases, by the presence or absence of HBsAg. It was concluded that the presence of proteinuria was considered as a good monitor of the kidney affection either with schistosomiasis or the nephrotic syndrome or the HBsAg. The detection of CIC can be used as a good monitor too and could be included in methods of early diagnosis and/or following the disease prognosis.     

Characteristics of lesions of paranasal sinuses in patients with optic chiasm arachnoiditis

The paper provides data on a comprehensive rhinological and x-ray examination of 201 patients suffering from optochiasmal arachnoiditis (OCA). Paranasal affection (as a rule polysinusitis) was disclosed in 75.6% of the examinees. The lesion occurred primarily in the sphenoidal sinuses and frequently combined with ethmoidal labyrinth and maxillary sinus involvement. Rhinological and x-ray symptoms in OCA are rarely prominent giving grounds to physicians for defining it as the syndrome of minor clinical signs. The latter hold importance for diagnosis which enables early cleansing of the paranasal sinuses in combined treatment of OCA.     

The John Charnley Award. Inhibition of wear debris mediated osteolysis in a canine total hip arthroplasty model

In this study the efficacy of an oral bisphosphonate therapy to inhibit wear debris mediated bone resorption was evaluated in a canine total hip replacement model. Adult canines were randomized to three groups (n = 8 each) with a right uncemented total hip replacement performed on each animal. Group I (control) received no particulate debris. In Groups II and III, a mixture of 1 x 10(9) particles were introduced into the proximal femoral gap intraoperatively. The particle mixture consisted of fabricated ultra high molecular weight polyethylene (mean 2.3 microns, 90% by number), titanium alloy (mean 3.1 microns, 5%), and cobalt chrome alloy (mean 0.8 micron, 5%). Group III canines additionally received oral drug therapy (5 mg once a day, alendronate sodium) which was begun on postoperative Day 7 and continued until the time of sacrifice. Postoperatively, all animals were allowed 24 weeks of full ambulation before euthanasia. Radiographs obtained preoperatively, postoperatively, and at time of sacrifice were evaluated for periprosthetic osteolysis. Interfacial tissues were examined histologically and placed in organ culture and the supernatants were assayed for prostaglandin E2 and interleukin-1. One animal receiving debris (Group II) suffered a periprosthetic fracture and was sacrificed from the study. Radiographically, one of eight Group I (control) and six of seven canines from Group II (debris) had periprosthetic radiolucencies with endosteal scalloping develop. In contrast, only one of eight animals from Group III (debris + alendronate) had periprosthetic radiolucencies develop. Whereas tissues from control animals were mostly fibrous and acellular, tissues from both experimental groups had significant macrophage infiltration. Levels of prostaglandin E2 and interleukin-1 were elevated significantly in periprosthetic tissues from both experimental groups compared with controls. Continuous administration of alendronate effectively inhibited bone lysis for the 24-week duration of the study. This is consistent with the literature indicating that alendronate is incorporated in the mineralizing matrix making it refractory to osteoclastic resorption. This report has significant clinical implications for controlling the most common cause of implant failure.     

Pediatric case of the day. Hinman syndrome (nonneurogenic bladder [NNNB], detrusor-sphincter dyssynergia)

Two cases of spontaneous left main coronary artery dissection are reported. This condition is rare and may present as an urgent surgical dilemma. The presentation, diagnosis, and management of primary left main coronary artery dissection are reviewed. Causative factors and underlying pathology are clarified. Prompt diagnosis and surgical intervention with temporary ventricular support is safe and effective.