Foscarnet and ganciclovir combination therapy for CMV disease in HIV-infected patients

Summary An open prospective trial of combined ganciclovir and foscarnet therapy for 3 weeks was initiated in 14 episodes of severe CMV-disease in 13 HIV-infected patients (all CDC class IV, age 30–42, median 34 years, CD4+ cell count 0–80, median 10/µl). In seven episodes of gastrointestinal disease (five colitis, two esophagitis) remission of symptoms and mucosal changes was achieved in five. In seven episodes of retinitis, scarring was achieved in six. Renal toxicity was seen in two patients, moderate hematologic toxicity in eight patients. Overall efficacy was comparable to monotherapy; no new toxicities were seen with the combination of these two drugs.

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Kombinationstherapie mit Ganciclovir und Foscarnet bei schwerer CMV-Erkrankung bei HIV-infizierten Patienten

Zusammenfassung In 14 Episoden einer CMV-Erkrankung bei 13 HIV-infizierten Patienten wurde eine Kombinationstherapie mit Ganciclovir und Foscarnet in einer offenen, prospektiven, nicht randomisierten Studie durchgeführt. Alle Patienten (n=13, Alter 30–42, Median 34 Jahre; CD4+Lymphozyten 0–80, Median 10/µl; alle Stadium IV CDC) wurden über 3 Wochen mit 2 × 5 mg/kg/d Ganciclovir und 2 × 90 mg/kg/d Foscarnet behandelt. In sieben Episoden einer gastrointestinalen CMV-Erkrankung (Colitis fünf, Ösophagitis zwei) wurde eine Remission in fünf Episoden erzielt, bei CMV-Retinitis in sechs von sieben Fällen. Nephrotoxizität trat bei zwei Patienten auf, mäßige Hämatotoxizität bei acht Patienten, sämtlich reversibel. Die Wirksamkeit der Therapie ist ähnlich der Monotherapie, die Nebenwirkungen sind additiv.

     

Low density lipoprotein receptor-dependent prostaglandin synthesis in Swiss 3T3 cells stimulated by platelet-derived growth factor.

We studied the effects of human plasma lipoproteins on the synthesis of prostaglandin (PG) E2 in Swiss 3T3 mouse fibroblasts. Quiescent cells, maintained in medium deficient in both platelet-derived growth factor (PDGF) and lipoproteins, synthesized less than 8 ng of PGE2 per 10(6) cells per 22 hr, and this rate did not change in response to the addition of lipoproteins. In contrast, PDGF-stimulated cells, incubated in medium deficient in lipoproteins, synthesized 45-110 ng of PGE2 per 10(6) cells during the same period of time, and this rate increased 2- to 5-fold in the presence of added low density lipoproteins (LDL). This stimulatory effect of LDL seemed to depend on LDL receptor-mediated binding, uptake, and degradation of the lipoproteins because: both LDL and very low density lipoproteins were active, whereas high density lipoproteins were not; low concentrations of LDL were effective; the effect of native LDL was blocked by acetylation of the LDL; PDGF increased both the expression of LDL receptors and the cellular uptake of LDL; chloroquine blocked the effect of LDL but not that of exogenous arachidonic acid. These results provide evidence that the LDL pathway is critically linked to PG synthesis in PDGF-stimulated cells.     

Cowpox virus infection associated with a streptococcal septicaemia in a foal

Cowpox virus infection associated with a streptococcal septicaemia was diagnosed in a weak German Warmblood filly, born 29 days prematurely, and humanely destroyed on the sixth day of life. At necropsy, ulcerative lesions in the alimentary tract, colitis, polyarthritis and nephritis were observed. Transmission electron microscopical examination of specimens from ulcerative lesions revealed typical orthopox virions. Cowpox virus was unequivocally identified by virological and molecular-biological methods.     

Ultrasonic surgery--an alternative way in orthognathic surgery of the mandible. A pilot study

The aim of this report is to present preliminary results and experiences using an ultrasonic bone-cutting device in bilateral sagittal split osteotomies of the mandible (BSSRO) with particular attention to possible damages to the inferior alveolar nerve (IAN). Seven patients with class II or class III malocclusion were treated by BSSRO with a conventional combined orthognathic and surgical approach. The osteotomy was carried out using an ultrasonic bone-cutting device. Subjective neurosensory deficits of the inferior alveolar nerve were assessed on 14 sides. Compared to the conventional techniques using saws, chisels and burs, the use of the ultrasonic device was more time-consuming, but the osteotomies were carried out at a high level of precision. In addition, this procedure offered the advantage of a blood-free surgical field and thus provided good control of the surgical procedure. Subjective neurosensory disturbances of the IAN showed a continuous decrease from 57.1% (eight sides) 2 months after the surgical procedure to 14.3% (2 sides) after 5 months and to 7.1% 7 months after BSSRO. Within the seven patients of this pilot study associated neurosensory disturbances were low. A possible advantage in terms of nerve protection is subject to a prospective study.     

Accuracy and clinical performance of a continuous intra-arterial blood- gas monitoring system during thoracoscopic surgery

Accuracy and performance of the only currently available intra-arterial blood-gas monitoring system (Paratrend 7, PT7) were assessed in 23 patients during thoracoscopic surgery using one-lung ventilation. Over a wide range of values for arterial PO2 (6.1-61.1 kPa), PCO2 (4.1-9.5 kPa) and pH (7.19-7.50), 138 arterial blood-gas values obtained by PT7 were compared with corresponding in vitro laboratory blood-gas measurements. We found good clinical performance with the PT7 and good agreement between PT7 values and in vitro measurements for arterial PO2 (bias (1.96 SD) = 0.38 (9.52) kPa), PCO2 (0.31 (0.76) kPa) and pH (- 0.017 (0.065)). Also, the bias for sequential changes between two, consecutive times was not significantly different from the ideal value of 0. We conclude that the PT7 is helpful in monitoring patients during thoracoscopy.      

Clindamycin pharmacokinetics and tissue penetration after head and neck surgery

Penetration of clindamycin into surgical wounds was studied in 10 patients undergoing radical head and neck surgery. Patients received one preoperative and three postoperative intravenous doses of clindamycin 600 mg. During surgery, samples of plasma and sternocleidomastoid muscle were obtained. Additional plasma samples were collected just before the fourth dose of clindamycin, just after that dose was infused, and 1, 2, 4, 6, 8, and 12 hours after dosing. Samples of wound exudate were collected at 2, 4, 6, 8, and 12 hours after the fourth dose. The muscle, plasma, and wound exudate samples were assayed for clindamycin base by a gas-liquid chromatographic method. Plasma and wound exudate samples obtained during surgery and one and eight hours after the fourth dose were assayed by a radial immunodiffusion technique for content of alpha 1-acid glycoprotein (AAG), the major binding protein for clindamycin. Pharmacokinetic values for plasma and wound drainage were calculated and compared. Concentrations of clindamycin in muscle (three to six hours after the first dose) ranged from 0.6 to 5.1 micrograms/g; the ratio of tissue to plasma concentrations ranged from 0.24 to 0.82. The highest mean clindamycin concentration in wound drainage was 4.9 micrograms/mL after the fourth dose, approximately 90% of simultaneous plasma concentrations. Concentrations in wound exudate exceeded those measured in plasma four hours after the dose, and elimination from the wound was slower than from plasma. AAG concentrations in plasma increased from a mean of 89 mg/dL intraoperatively to 134 mg/dL postoperatively. AAG was present in wound exudate in concentrations that were approximately 53% of those observed in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular heterogeneity of sporadic adult Burkitt-type leukemia/lymphoma as revealed by PCR and cytogenetics: correlation with morphology, immunology and clinical features.

Chromosomal translocations involving the MYC oncogene are a hallmark of Burkitt lymphoma but they are only found in a varying frequency in mature Burkitt-type acute lymphoblastic leukemia (B-ALL). We have investigated samples of 56 sporadic Burkitt leukemia/lymphoma patients for the translocations t(8;14)(q24;q32), t(2;8)(p11;q24) and t(8;22)(q24;q11). Long PCR was used for detecting the immunoglobulin heavy chain (IgH) translocation and cytogenetics and/or fluorescence in situ hybridization for detecting the 'variant' MYC translocations. A total of 29 samples (51.8%) were t(8;14)-positive by long PCR. Approximately one-third had a chromosomal breakpoint in the IgH joining region while the others had breakpoints in the IgH switch regions. Among them were two cases with a previously unreported MYC translocation into the IgE switch region. Long PCR was more reliable compared to conventional cytogenetics for detecting the t(8;14). Epstein-Barr virus was detected in high copy number in two (3.6%) t(8;14)-positive cases by real-time quantitative PCR. Human herpesvirus 8 was not detected in any case by nested PCR. A typical L3 or L3-compatible cytomorphology was highly predictive (>80%) but not specific of a MYC translocation. A total of 34 patients were treated according to the GMALL B-ALL therapy protocols and there was no significant difference in overall survival between patients with or without t(8;14).     

p53 Codon 72 polymorphism, loss of heterozygosity and high-risk human papillomavirus infection in a low-incidence German esophageal squamous cell carcinoma patient cohort

Epidemiological studies in endemic geographic regions for esophageal squamous cell carcinoma (ESCC) suggested a number of risk factors, including modifications of the p53 tumor suppressor by codon Arg72Pro polymorphism, loss of heterozygosity (LOH) or human papillomavirus type 16 or 18 (HPV 16/18) infection. The p53 Arg72 variant has been suggested to be a high-risk factor in HPV-associated tumors. The present study analysed these associations in a low incidence geographic region in Germany. Fifty-three paraffin-embedded tumors and 53 surrounding normal squamous epithelium were investigated. For detection of p53 codon Arg72Pro polymorphism, direct sequencing for exon 4 was conducted. LOH analysis was performed using three microsatellite markers at the p53 gene locus, and all cases were screened for high-risk HPV infection (HPV 16 and 18) with primer specific PCR and confirmed by sequencing. The p53 codon 72 genotype distribution was identical to published studies of normal Caucasian population, suggesting no general influence of this polymorphism on esophageal cancer risk in Germany. One case showed a p53 mutation in exon 4. p53 LOH was found in 13/44 (30%) informative cases without any correlation to histopathological characteristics. Of 53 (17%) samples, 9 showed HPV 16 or 18 infection. We found no association between p53 codon 72 genotypes and increasing HPV infection rates. Interestingly, 8/9 HPV-positive cases showed at least one p53 Arg72 allele. These results indicate an important role of p53 in ESCC also in low-incidence regions. In combination with the p53 Arg72 variant HPV infection could contribute to the risk of ESCC development in these cases, as has been demonstrated for high-risk regions.