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K Leder

Publications and source records attributed to K Leder.

At least 19 recordsLinked to original sources
PubMed2001

Travel vaccines and elderly persons: review of vaccines available in the United States.

Aging is associated with alterations in immune responses and may lead to clinically significant changes in the safety, immunogenicity, and protective efficacy of certain vaccines. This review summarizes published data regarding the effects of age on responses after immunization with vaccines generally administered before travel. The specific vaccines discussed in detail include hepatitis A, typhoid, yellow fever, Japanese encephalitis, and rabies vaccines. There is some evidence of diminished serological responses to hepatitis A and rabies vaccines in older individuals. In addition, increased toxic effects following yellow fever vaccination in elderly recipients have recently been reported. However, many travel-related vaccines have never been studied specifically in elderly populations. Consideration of potential age-related differences in responses to travel vaccines is becoming increasingly important as elderly persons more frequently venture to exotic destinations.

Aged↗
PubMed2001

Cyclin D1 polymorphism and expression in patients with squamous cell carcinoma of the head and neck.

We have previously reported that the cyclin D1 (CCND1) GG870 genotype was associated with poorly differentiated tumors and reduced disease-free interval in patients with squamous cell carcinoma of the head and neck (SCCHN). We have now examined the association of this and a second CCND1 polymorphism with gene expression and outcome in SCCHN patients. Analysis of a CCND1 G/C1722 polymorphism revealed that CCND1 CC1722 genotype was associated with poorly differentiated tumors [P = 0.005; odds ratio (OR), 5.7; 95% CI, 1.7 to 19.2), and reduced disease-free interval (P = 0.003; Hazard Ratio (HR), 7.3; 95% CI, 1.1 to 27.2.) independently from the influence of CCND1 GG870 genotype. Patients whose tumors were negative for cyclin D1 were associated with reduced disease-free interval (P = 0.028; HR, 4.1; 95% CI, 1.4 to 14.2). Although G/C1722 genotypes were not associated with expression, we found a significant trend between reduced expression of cyclin D1 in patients with the CCND1 GG870 genotype (P = 0.04). Splicing of CCND1 mRNA in head and neck tissues was modulated by CCND1 A/G870 alleles, thus CCND1 transcript a was spliced equally from CCND1 A870 and G870 alleles, whereas CCND1 transcript b was spliced mainly from the CCND1 A870 allele. Our analysis has also identified differences in cyclin D1 genotype and protein expression and the pathogenesis of SCCHN in males and females. Thus, CCND1 CC1722 genotype was more common in female patients (P = 0.019; OR, 3.3; 95% CI, 1.3 to 10) and cyclin D1 expression was more frequent (chi-square1, 3.96; P = 0.046) and at higher levels (P = 0.004) in tumors from female patients. In summary, our data show that the two CCND1 polymorphic sites are independently associated with tumor biology and clinical outcome. CCND1 A/G870 alleles affect gene expression in head and neck tissues. We also provide preliminary evidence that the molecular genetics of SCCHN development may be influenced by patient gender.

Alleles↗
PubMed2000

Bacterial translocation during graft-versus-host disease after small bowel transplantation is reduced following inhibition of inducible nitric oxide synthesis.

BACKGROUND: Increased nitric oxide (NO) production may contribute to intestinal barrier dysfunction and increased bacterial translocation (BT). Since BT may play a major role in graft-versus-host disease (GVHD) after small bowel transplantation (SBTx), we evaluated the role of NO production in GVHD after SBTX in the rat. METHODS: Using the standard model of semiallogeneic SBTx in the rat, we prepared three experimental groups. Recipients in group 1 received LBNF1-LBNF1 transplants and were treated with aminoguanidine (AG) (200 mg/kg), recipients in group 2 received Lewis-LBNF1 grafts and were injected with saline, and recipients in group 3 received Lewis-LBNF1 transplants and AG (200 mg/kg). Urine nitrite/nitrate levels were measured daily, and BT was determined by culturing peritoneal swabs, mesenteric lymph nodes, spleen, liver, and blood. RESULTS: In group 1 we detected indefinite survival with normal histology. In group 2 a survival of 10.5 +/- 1.1 days was reached, and the typical histological features of acute GVHD were observed. The animals in group 3 showed a mean survival of 14.8 +/- 0.6 days (P<0.02 compared with group 2) and the histological features of acute GVHD, although with a prolonged time course. Comparing NO production and BT between groups 2 and 3 we detected significantly reduced NO production on postoperative days 2-9 (P<0.03) and significantly decreased BT on postoperative days 3 and 9 (P<0.03). CONCLUSION: Inhibition of inducible NO synthesis with AG reduces NO production, decreases BT, and prolongs survival during GVHD after SBTx and therefore may be a useful addition to standard treatment protocols for GVHD.

Animals↗
PubMed2000

CD5-positive B cells in healthy elderly humans are a polyclonal B cell population.

B cell chronic lymphocytic leukemia (B-CLL) is a disease of the elderly and is characterized by a malignant clone of CD5+ B cells. In old mice, clonal expansions of CD5+ B cells are a common feature, and these animals frequently develop B-CLL. To investigate whether clonal expansion of CD5+ B cells also occurs in elderly humans, predisposing for the development of B-CLL, we analyzed VH gene rearrangements of CD5+ B cells from blood samples of four healthy, 65-82-years-old volunteers as markers of clonality. CD5+ and CD5-B cells were obtained by cell sorting, CDRIII of rearranged VH genes were amplified by polymerase chain reaction, and fragment length analysis was performed. All samples demonstrated a polyclonal pattern of VH gene length distribution. In addition, VH gene rearrangements were amplified and sequenced from sorted single cells of two of the donors. No clonally related CD5+ or CD5- B cells were observed. Thus, development of dominant clones of CD5+ peripheral blood B cells is unlikely to be a common trait of elderly individuals.

Aging↗
PubMed2000

Eosinophilia and helminthic infections.

Among microbial agents, helminths are the most common cause of eosinophilia. An approach to the evaluation of a patient with eosinophilia is outlined, with particular emphasis on clues in the history, examination and routine laboratory data that can help with the diagnosis. Multiple helminthic infections have been associated with eosinophilia, and the characteristic modes of spread, clinical manifestations, diagnostic tests and therapeutic considerations of these infections are discussed.

Animals↗
PubMed1999

Occurrence of a novel DNA virus (TTV) infection in patients with liver diseases and its frequency in blood donors.

A novel DNA virus (TTV) was identified recently in Japanese patients with posttransfusion hepatitis non-A-E and has been implicated as a cause of acute and chronic liver diseases of unknown etiology in some patients. The frequency of TTV infections was investigated in 284 blood donors, 105 patients with different liver disorders before and after liver transplantation (OLT), as well as in 64 patients with chronic hepatitis C who received antiviral therapy. TTV infections were found more frequently by nested-PCR in patients with liver disorders (15%) as compared to blood donors (7%). TTV occurred independently of the aetiology of the liver disease (e.g., cryptogenic cirrhosis [12.5%], alcoholic cirrhosis [16%], fulminant hepatic failure non-A-E [35%], and chronic hepatitis C [12.5%]; p=n.s.). After OLT, a high rate of TTV de novo infections (44%) was observed. However, TTV viremia after OLT (in 56 out of the 105 patients) was not associated with graft hepatitis. Analysis of patients with chronic hepatitis C coinfected with TTV who have been treated with interferon alpha alone or in combination with ribavirin revealed that TTV is an interferon-sensitive virus. Phylogenetic analysis of TTV sequences suggest that at least four different genotypes and several subtypes exist in Germany. In conclusion, the high prevalence of TTV infections observed in patients with parenteral risk factors is an argument in favour of transmission of the virus via blood and blood products. A relevant hepatitis-inducing capacity of TTV, however, seems unlikely, considering the observation that in the majority of patients, TTV infection after OLT was not accompanied by graft hepatitis.

Adolescent↗
PubMed1999

The clinical efficacy of continuous-infusion flucloxacillin in serious staphylococcal sepsis.

Since the efficacy of beta-lactams against pathogens such as methicillin-susceptible Staphylococcus aureus (MSSA) is related to the time for which serum drug concentrations exceed the MIC for the pathogen, administration of anti-staphylococcal beta-lactams by continuous infusion may provide a more suitable means of drug delivery than intermittent dosing. To assess the clinical efficacy of continuous-infusion therapy, we reviewed the outcomes for 20 consecutive patients with proven serious MSSA sepsis (three with endocarditis, ten osteomyelitis, one endocarditis plus osteomyelitis and six deep abscess) treated with continuous-infusion flucloxacillin (8-12 g/day). Patients initially receiving routine intermittent-dose flucloxacillin therapy were changed to continuous-infusion flucloxacillin (mean duration 29 days; range 4-60 days) for completion of their treatment course. In the majority of cases this was given at home. Serum flucloxacillin concentrations during continuous-infusion flucloxacillin 12 g/day were 11.5->40 mg/L (ten patients) and those during continuous-infusion flucloxacillin 8 g/day were 8->40 mg/L (five patients), these concentrations being well above the expected MIC of flucloxacillin for MSSA. Continuous-infusion flucloxacillin was well tolerated by most patients, and 14/17 patients (82%) who completed their course of continuous-infusion flucloxacillin were judged clinically and microbiologically cured at long-term follow-up (mean 67 weeks; range 4-152 weeks). These preliminary data suggest that, following initial intermittent-dose flucloxacillin therapy, continuous-infusion flucloxacillin is an effective treatment option for serious MSSA sepsis, and forms a feasible and possibly preferable alternative to glycopeptides when considering home-based parenteral therapy for these infections. Further studies are needed to identify whether continuous-infusion flucloxacillin can entirely replace intermittent-dose therapy for such infections.

Adolescent↗
PubMed1998

Home-based treatment of cellulitis with twice-daily cefazolin.

OBJECTIVE: To assess the clinical outcome and pharmacokinetics of therapy with cefazolin for patients with cellulitis in a hospital-in-the-home (HIH) program. DESIGN: Observational study with outcome data compared with previously published reports of therapy for cellulitis. SETTING: A university teaching hospital and HIH unit, July 1996-December 1997. PARTICIPANTS: Patients with cellulitis were eligible for inclusion provided their medical condition was stable, they did not require surgical intervention, and their social circumstances allowed home-based therapy. INTERVENTION: Cefazolin 2 g intravenously twice daily, with regular nursing and medical assessment. MAIN OUTCOME MEASURES: Clinical efficacy; peak and trough serum concentrations of cefazolin. RESULTS: Fifty-seven patients (37 were men) with a mean age of 48 years (range, 18-90 years) had 61 episodes of moderate to severe cellulitis (41, lower limb; 17, upper limb; and three, face). They received a median of 11 doses of cefazolin (range, 3-27 doses). Clinical outcomes were: cure in 54, improvement in one, treatment failure in three, and in the remaining three episodes the outcome was indeterminate. Cefazolin concentrations were measured in 27 patients. All peak concentrations were more than 40 micrograms/mL, while trough concentrations were all above the MIC90 of the expected pathogens: median, 3.2 micrograms/mL (range: 0.4-18.5 micrograms/mL). Cefazolin was well tolerated. CONCLUSIONS: Twice-daily cefazolin 2 g intravenously is a convenient and effective option for home-based treatment of patients with cellulitis. Its clinical efficacy is comparable with other treatment regimens.

Administration, Oral↗
PubMed1998

[Partial sphincterectomy in cataract surgery. Clinical and patho-histologic results].

BACKGROUND: We perform partial sphincterectomy during cataract surgery in cases with very small pupil (< 3 mm). We assume that the small pupil is mainly due to a fibrosis ring of the sphincter muscle. PATIENTS: In 35 patients we performed the complete ophthalmological routine checkup. The pupil diameter was analysed by perimeter: a base value, with light, and in pharmaceutical mydriasis. Moreover 15 preparations were analysed histologically. RESULTS: Average pupil diameter was: base value 3.76 mm, with light 3.24 mm, in pharmaceutical mydriasis 4.84 mm. The showed pathohistological examination that in all excisions a part of the sphincter muscle was verifiable. We found fibrosis of different grades in various locations. CONCLUSION: In most cases functional pupil movement can be verified after operation. In an intended partial sphincterectomy part of the sphincter muscle can be excised. The different pupil diameter is due to the different degree of fibrosis of the sphincter muscle.

Adult↗
PubMed1998

Microsporidial disease in HIV-infected patients: a report of 42 patients and review of the literature.

Microsporidiosis is recognized as an increasingly important infection, particularly in patients with human immunodeficiency virus (HIV) infection. In this retrospective study we have reviewed the clinical features, laboratory findings and management of 42 HIV positive patients co-infected with microsporidia. All patients had spores identified in faeces stained with a modified trichome blue stain. Patients were all markedly immunosuppressed (median CD4 20 cells/microl). Common symptoms included weight loss, diarrhoea, abdominal pain, anorexia and nausea. 29 patients were diagnosed with Enterocytozoon bieneusi infection; 13 were infected with Encephalitozoon intestinalis, and disseminated disease was confirmed in 8. Albendazole therapy in patients with E. intestinalis (but not E. bieneusi) resulted in good clinical response.

Adult↗
PubMed1998

"Flexispira rappini" bacteremia in a child with pneumonia.

We describe a case of "Flexispira rappini" bacteremia from a 9-year-old girl who presented with a 5-day history of fever, productive cough, and malaise. A chest X-ray result was compatible with right middle lobe pneumonia. Blood culture grew a gram-negative spiral fusiform bacterium 2 days after the inoculation. Biochemical tests showed the organism to be catalase negative, oxidase positive, sodium hippurate hydrolysis negative, and urea hydrolysis negative. 16S rRNA gene sequencing identified this organism as "F. rappini," showing a six-base substitution from the type strain. This is the first report of "F. rappini" bacteremia in a human, suggesting that this organism has the potential of causing invasive infection, but its role in pneumonia is uncertain and could be unrelated to the bacteremia.

Bacteremia↗
PubMed1998

Polymorphism within the cyclin D1 gene is associated with prognosis in patients with squamous cell carcinoma of the head and neck.

We have examined the correlation of a frequent A/G polymorphism within exon 4 of the cyclin D1 gene (CCND1) with genetic susceptibility and clinical outcome in 384 patients with squamous cell carcinoma (SCC) of the head and neck. CCND1 genotype frequencies were similar in the cases and 191 controls. Furthermore, the CCND1 genotype was not associated with susceptibility to SCC of the larynx, pharynx, or oral cavity. The influence of the CCND1 genotype on clinical outcome was also assessed. We found no correlation between genotype and tumor size (T1-T4), the involvement of nodes at presentation, or patient age and gender. However, the distribution of CCND1 genotypes in cases with poorly differentiated tumors was significantly different to that in patients with well-/moderately differentiated tumors (P = 0.016; chi2(2) = 8.71). Homozygosity for CCND1*G (GG genotype) was associated with poorly differentiated tumors (G3). We used Cox's proportional hazards model to investigate the influence of the CCND1 genotype on disease-free interval. CCND1 GG was associated with reduced disease-free interval [P = 0.001; hazard ratio (HR) = 2.95; 95% confidence interval (CI) = 1.54-5.63]. This remained significant after correction for tumor differentiation (P = 0.013; HR = 2.34; 95% CI = 1.2-4.6) and tumor stage (P = 0.005; HR = 2.64; 95% CI = 1.34-5.19). Analysis of the data from patients with tumors at different sites showed that the CCND1 GG genotype was associated with reduced disease-free interval in laryngeal (P = 0.004; HR = 3.63; 95% CI = 1.44-8.83) and pharyngeal (P = 0.006; HR = 3.48; 95% CI = 1.43-8.46) tumors. This is the first report of an association between CCND1 polymorphism and prognosis in SCC of the head and neck. These data show that the CCND1 GG genotype is an independent prognostic indicator of disease-free interval and supports initial observations in non-small cell lung cancer, that polymorphism within CCND1 influences tumor behavior.

Adult↗
PubMed1997

A pretransplant infection with precore mutants of hepatitis B virus does not influence the outcome of orthotopic liver transplantation in patients on high dose anti-hepatitis B virus surface antigen immunoprophylaxis.

Hepatitis B virus (HBV) infection of the liver graft is a major complication after orthotopic liver transplantation (OLT) for HBV-related cirrhosis. A high viral load before OLT is a known risk factor, whereas the relevance of precore mutants of HBV is a subject of controversy. The aim of this study was to correlate the pretransplantation viral load and a pretransplantation infection with precore mutant HBV (pmHBV) or wildtype HBV (wtHBV) with allograft damage, graft failure, and survival after OLT. Sixty-nine patients with HBV cirrhosis underwent OLT under high dose immunoprophylaxis with anti-hepatitis B surface (HBs) hyperimmunoglobulins (HBIg). A pretransplantation infection with pmHBV and wtHBV was detected by polymerase chain reaction (PCR) and direct sequencing in 30 patients each (pmHBV and wtHBV group). Nine of 69 patients were PCR-negative (noHBV group). Median pretransplantation levels of HBV DNA assessed by hybridization assay were 42 pg/mL for pmHBV and 54 pg/mL for wtHBV patients. HBV recurred in 17 of 30 (57%) of pmHBV and in 14 of 30 (47%) of wtHBV patients and graft failure occurred in 6 of 30 (20%) of pmHBV and 7 of 30 (23%) of wtHBV patients. Neither HBV recurrence nor graft failure occurred in patients in whom no HBV DNA could be detected by PCR using primers flanking the HBV precore region (noHBV) patients. Allograft damage assessed by histology activity index (HAI) scoring was median 6 for pmHBV and 7 for wtHBV patients. Cumulative survival after 5 years was 72% for pmHBV, 74% for wtHBV, and 100% for noHBV patients. In this study, we provide evidence that pretransplantation viral load, but not infection with pmHBV, determines the outcome after OLT in patients on high dose HBIg prophylaxis.

Adult↗
PubMed1994

The effect of FK506 versus cyclosporine on glucose and lipid metabolism--a randomized trial.

In order to evaluate the effect of cyclosporine (CsA) versus FK506 on glucose and lipid metabolism, an oral glucose tolerance test (OGTT) was performed in 101 patients after orthotopic liver transplantation (OLT) (mean interval after OLT: 511 days). The liver graft recipients had been randomized prospectively to two groups prior to OLT to receive either immunosuppression with CsA, azathioprine, and corticosteroids (CsA group) or FK506 and corticosteroids (FK group). Along with the OGTT, serum insulin, insulin C-peptide and glucagon as well as serum lipids were monitored. There was no statistically significant difference in the occurrence of impaired glucose tolerance (IGT) or manifest diabetes mellitus disease between the two groups. In fact, not a single patient developed new-onset diabetes in any group. In male and female patients, serum levels of cholesterol and triglycerides increased significantly under FK506 and CsA treatment after OLT. Cholesterol was significantly higher in the CsA group in men, in women this was marked, but not significant. While triglycerides were significantly higher in women on CsA treatment, there was no such difference in men. In conclusion, both CsA and FK506 proved to have similar effects on glucose metabolism, while there was a different spectrum of serum lipid alterations.

Adolescent↗
PubMed1994

[Osteonecrosis].

The causes of osteonecrosis are varied. The pathogenesis of osteonecrosis subsequent to trauma is well known. Furthermore, an association of this disorder with cortisone, haemoglobinopathies, rare metabolic diseases, and risk factors seems to be evident. However, a sizable proportion of patients have osteonecrosis in which none of these associations exists, referred to as idiopathic osteonecrosis. Generally, intraosseous vascularization represents the common pathway for the various causes of the disease. The prognosis is influenced by the age of the patient, the location of the necrosis and the stage of the disease at the time of diagnosis. In recent times diagnosis has been improved by the use of modern imaging modalities, and MR imaging is now widely accepted as the imaging method of choice. It not only allows early diagnosis but also yields exact staging information in advanced disease, which is a requirement for adequate therapy.

Adult↗
PubMed1994

[The non-traumatic femur head necrosis in the adult. I: pathophysiology, clinical picture and therapeutic options].

Intraosseous vascularization is the common pathway of the multifactorial causes of avascular necrosis of the hip (AVN). Recurring ischemic phases could lead to bone necrosis in the initial stage of the disease, when it is still reversible. A spontaneous repair mechanism can lead to complete healing at this stage. The necrotic area demarcates the superior-anterior aspect from the residual femoral head with a reactive interface in the irreversible early stage of the disease. In this stage damage to the femoral head can only be delayed with core decompression or femoral osteotomy, because a sufficient repair mechanism is no longer possible. When the articular surface collapses the early stage gives way to the late stage. Cartilage incongruence and microfracture lead to progressive destruction of the femoral head and to secondary osteoarthritis. In this late stage femoral osteotomy is only successful in carefully selected patients. Total hip replacement is the last resort for patients with painful destruction of the joint. As clinical symptoms are unspecific, MRI plays an important role for early diagnosis of AVN in the initial or early stages. Conservative treatment is not successful in any of the three stages of the disease.

Adult↗
PubMed1993

[Bone marrow edema--an early form of femur head necrosis].

We examined 15 patients (16 hips) with painful hips whose radiographs were either normal (n = 9) or showed a minimal decrease in radiodensity (n = 7). The available bone scintigrams of 9 cases were positive. T1-weighted images visualised a diffuse signal loss of the bone marrow in all hips, with various extensions in the head, neck, and intertrochanteric area. These regions were hyperintensive on T2-weighted images. Focal anomalies were not seen in any of the cases. All patients underwent core decompression treatment. Histology of 13 hips confirmed not only the presence of bone marrow oedema but of bone changes corresponding to those of avascular necrosis. Follow-up examinations with MR after core decompression showed normal signal intensity in all cases. Magnetic resonance represents a viable diagnostic tool for identifying bone marrow oedema. Due to our histological results bone marrow oedema should be included in the differential diagnosis as an early stage of necrosis of the hip.

Adult↗