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Biomedical subjects

B Suh

Publications and source records attributed to B Suh.

At least 19 recordsLinked to original sources

Aspergillus mediastinitis following orthotopic heart transplantation: case report and review of the literature.

Bacterial mediastinitis after orthotopic heart transplantation (OHT) is well described in the literature. However, little information has been published on fungal mediastinitis in this population. We describe a man with Aspergillus fumigatus mediastinitis diagnosed 10 weeks after OHT. The patient was treated with voriconazole. The literature on Aspergillus mediastinitis is also reviewed.

Antifungal Agents↗

Infective endocarditis following orthotopic heart transplantation: 10 cases and a review of the literature.

BACKGROUND: Infective endocarditis is a known complication of cardiac transplantation. However, published information has been limited to case reports and small case series. METHODS: Cardiac transplantation has been performed at Temple University Hospital since 1983. We identified transplant patients with ICD-9 codes for endocarditis or bacteremia. A diagnosis of endocarditis required fulfillment of the Duke criteria and presence of a vegetation. Clinical and microbiologic data were collected. Demographic and survival information were compared with heart transplant recipients without endocarditis. We reviewed all previously published cases using a MEDLINE search. RESULTS: Ten of 659 heart transplant recipients had endocarditis (1.5%, 187 cases per 100,000 person years). Mitral and tricuspid valves were involved predominantly. No patient had aortic valve infection. Patients with tricuspid valve infection had a greater median number of endomyocardial biopsies (n=23) than those with mitral valve infection (n=9, P=0.10). The major pathogens were Staphylococcus aureus (4 cases) and Aspergillus fumigatus (3 cases). Factors associated with S. aureus infection were new hemodialysis catheters, cellulitis, and a contaminated donor organ. All patients with A. fumigatus had antecedent cytomegalovirus viremia and disseminated fungal infection, including endophthalmitis. Endocarditis-related mortality was 80%. Median survival after transplant was 1.4 years in patients with endocarditis, compared with 9.3 years in other heart transplant recipients (P<0.001). CONCLUSIONS: Endocarditis is substantially more common in heart transplant recipients than in general populations. Frequent central venous catheter access and multiple endomyocardial biopsies appear to predispose to infection. Aspergillus is a common pathogen and endocarditis follows infection elsewhere. The prognosis of post-cardiac transplant endocarditis is poor.

Adult↗

Helicobacter pylori infection: epidemiology, pathophysiology, and therapy.

Helicobacter pylori is one of the most commonly encountered human pathogens. It has been shown to be closely associated with peptic ulcer disease (PUD), gastric adenocarcinoma, and the gastric mucosa-associated lymphoid tissue (MALT) that may lead to gastric lymphoma. The current diagnostic methods include histology, microbiological culture, classic serology, urease activity detection, polymerase chain reaction (PCR) and stool antigen detection. Its treatment modality options are multiple; however, a triple regimen consisting of a proton pump inhibitor (PPI), and two antibiotics for 10 to 14 days is preferred. Drug resistance is a growing problem in this organism and new therapeutic options are currently limited.

Adenocarcinoma↗

Antiretroviral therapy 2000.

As we enter the new millennium, there have been dramatic improvements in the care of patients with HIV infection. These have prolonged life and decreased morbidity and mortality. There are fourteen currently available antiretrovirals approved in the United States for the treatment of this infection. The medications, including their pharmacokinetic properties, side effects, and dosing are reviewed. In addition, the current approach to the use of these medicines is discussed.

Anti-HIV Agents↗

Clinical features and treatment of Malassezia folliculitis with fluconazole in orthotopic heart transplant recipients.

Orthotopic heart transplant recipients need immunosuppressive treatment and are at an increased risk for opportunistic infections such as Malassezia folliculitis. During a 4-month period (July to October 1990), 11 such cases were identified and treated; all were male with mean age of 43+/-9 years and on standard triple immunosuppressive therapy. Skin scrapings in potassium hydroxide (KOH) preparation with microscopy and/or culture identified either Malassezia furfur or Malassezia pachydermatis as the etiologic agent. A treatment with topical preparation (clotrimazole 1% and selenium sulfide lotion) was effective in 6 patients, whereas the rest received systemic fluconazole treatment with satisfactory outcome; all lesions were resolved within 3 weeks. Fluconazole appears to be an effective agent with excellent therapeutic outcome when administered for 3 weeks.

Adult↗

Clinical efficacy of intravenous followed by oral azithromycin monotherapy in hospitalized patients with community-acquired pneumonia. The Azithromycin Intravenous Clinical Trials Group.

The purpose of this study was to evaluate intravenous (i.v.) azithromycin followed by oral azithromycin as a monotherapeutic regimen for community-acquired pneumonia (CAP). Two trials of i.v. azithromycin used as initial monotherapy in hospitalized CAP patients are summarized. Clinical efficacy is reported from an open-label randomized trial of azithromycin compared to cefuroxime with or without erythromycin. Bacteriologic and clinical efficacy results are also presented from a noncomparative trial of i.v. azithromycin that was designed to give additional clinical experience with a larger number of pathogens. Azithromycin was administered to 414 patients: 202 and 212 in the comparative and noncomparative trials, respectively. The comparator regimen was used as treatment for 201 patients; 105 were treated with cefuroxime alone and 96 were given cefuroxime plus erythromycin. In the comparative trial, clinical outcome data were available for 268 evaluable patients with confirmed CAP at the 10- to 14-day visit, with 106 (77%) of the azithromycin patients cured or improved and 97 (74%) of the comparator patients cured or improved. Mean i.v. treatment duration and mean total treatment duration (i.v. and oral) for the clinically evaluable patients were significantly (P < 0.05) shorter for the azithromycin group (3.6 days for the i.v. group and 8.6 days for the i.v. and oral group) than for the evaluable patients given cefuroxime plus erythromycin (4.0 days for the i.v. group and 10.3 days for the i.v. and oral group). The present comparative study demonstrates that initial therapy with i.v. azithromycin for hospitalized patients with CAP is associated with fewer side effects and is equal in efficacy to a 1993 American Thoracic Society-suggested regimen of cefuroxime plus erythromycin when the erythromycin is deemed necessary by clinicians.

Administration, Oral↗

Duplicate genes for Fe-containing superoxide dismutase in Streptomyces coelicolor A3(2).

Streptomyces coelicolor Müller contains two types of superoxide dismutase (SOD) containing Ni (encoded by sodN) or Fe (encoded by sodF). Unlike a single species of Fe-containing SOD in Müller strain, multiple forms of FeSODs were detected in S. coelicolor A3(2) strain by activity staining and Western blot analysis. Genomic Southern hybridization suggested the presence of at least two copies of the sodF-like gene in A3(2). Two different genes for FeSOD (sodF1 and sodF2) were isolated from the phage library of A3(2) genome. The nucleotide sequence of the sodF1 coding region was identical with the unique sodF gene from Müller while that of sodF2 shared 88% identity. The gene products of sodF1 and sodF2 were identified by activity staining and immunoblot analysis. Expression from the sodF1 gene was repressed by nickel as sensitively as Müller sodF, suggesting the presence of Ni-responsive regulatory site within the region shared by the two genes. Among 12 other Streptomyces species examined, only S. fradiae contained two FeSOD-like polypeptides. We postulate that the additional copy of the sodF gene (sodF2) was provided by the horizontal transfer from remotely related bacteria.

Amino Acid Sequence↗

Transcriptional and post-transcriptional regulation by nickel of sodN gene encoding nickel-containing superoxide dismutase from Streptomyces coelicolor Müller.

A novel type of superoxide dismutase containing nickel as a cofactor (NiSOD) has been discovered in several Streptomyces spp. The gene for NiSOD (sodN) was cloned from S. coelicolor Müller using degenerate oligonucleotide probes designed from the N-terminal peptide sequence of the purified enzyme. It encodes a polypeptide of 131 amino acids (14703 Da), without any apparent sequence similarity to other known proteins. The N-terminus of the purified NiSOD was located 14 amino acids downstream from the initiation codon of the deduced open reading frame (ORF), indicating the involvement of protein processing. The molecular mass of the processed polypeptide was predicted to be 13201 Da, in close agreement with that of the purified NiSOD (13.4 kDa). The transcription start site of the sodN gene was determined by S1 mapping and primer extension analysis. Ni2+ regulates the synthesis of NiSOD polypeptide. S1 mapping of both 5' and 3' ends of sodN mRNA revealed that Ni2+ increased the level of monocistronic sodN mRNA by more than ninefold without changing its half-life, thus demonstrating that Ni2+ regulates transcription. Both precursor and processed NiSOD polypeptides with little SOD activity were produced from the cloned sodN gene in S. lividans in the absence of sufficient Ni2+; however, on addition of Ni2+, active NiSOD consisting of only processed polypeptide was formed. Expression of the full-length sodN gene in E. coli produced NiSOD polypeptide without any SOD activity even in the presence of Ni2+. However, deletion of nucleotides encoding the N-terminal 14 amino acids from the sodN gene allowed the production of active NiSOD in E. coli, indicating that N-terminal processing is required to produce active NiSOD. These results reveal the unique role of nickel as a multifaceted regulator in S. coelicolor controlling sodN transcription and protein processing, as well as acting as a catalytic cofactor.

Amino Acid Sequence↗

Expression and regulation of the sodF gene encoding iron- and zinc-containing superoxide dismutase in Streptomyces coelicolor Müller.

Streptomyces coelicolor Müller contains two superoxide dismutases (SODs), nickel-containing (NiSOD) and iron- and zinc-containing SOD (FeZnSOD). The sodF gene encoding FeZnSOD was isolated by using PCR primers corresponding to the N-terminal peptide sequence of the purified FeZnSOD and a C-terminal region conserved among known FeSODs and MnSODs. The deduced amino acid sequence exhibited highest similarity to Mn- and FeSODs from Propionibacterium shermanii and Mycobacterium spp. The transcription start site of the sodF gene was determined by primer extension. When the sodF gene was cloned in pIJ702 and introduced into Streptomyces lividans TK24, it produced at least 30 times more FeZnSOD than the control cells. We disrupted the sodF gene in S. lividans TK24 and found that the disruptant did not produce any FeZnSOD enzyme activity but produced more NiSOD. The expression of the cloned sodF gene in TK24 cells was repressed significantly by Ni, consistent with the regulation pattern in nonoverproducing cells. This finding suggests that the cloned sodF gene contains the cis-acting elements necessary for Ni regulation. When the sodF mRNA in S. coelicolor Muller cells was analyzed by S1 mapping of both 5' and 3' ends, we found that Ni caused a reduction in the level of monocistronic sodF transcripts. Ni did not affect the stability of sodF mRNA, indicating that it regulates transcription. S. lividans TK24 cells overproducing FeZnSOD became more resistant to oxidants such as menadione and lawsone than the control cells, suggesting the protective role of FeZnSOD. However, the sodF disruptant survived as well as the wild-type strain in the presence of these oxidants, suggesting the complementing role of NiSOD increased in the disruptant.

Amino Acid Sequence↗

In vitro activity of beta-lactamase inhibitors against clinical isolates of Acinetobacter species.

Acinetobacter is an important cause of nosocomial infections, and it is often resistant to many antibiotics. In a search for alternative agents, three beta-lactamase inhibitors (sulbactam, clavulanate, and tazobactam) and five beta-lactam antibiotics (imipenem, ceftazidime, ceftriaxone, cefotaxime, and piperacillin) were tested against 68 unique clinical isolates of Acinetobacter species. Minimum inhibitory concentrations were determined by a broth microdilution method. Using temperature sensitivity testing, we identified 59 strains as Acinetobacter baumannii, one as Acinetobacter haemolyticus, and eight as indeterminate biotype species. We demonstrated 41 of 59 (70%) strains of A. baumannii to be multiply resistant (susceptible only to amikacin and imipenem), whereas all the nonbaumannii strains were not. Imipenem was the most active agent among the compounds investigated. All three beta-lactamase inhibitors had strong intrinsic activity, with sulbactam being the most active agent among the beta-lactamase inhibitors studied.

Acinetobacter↗

Quinolones.

Fluoroquinolones represent a major advance in antimicrobial chemotherapy. Currently, there are five fluoroquinolones approved by the FDA, and many more quinolones are expected to become available in years to come. Although their clinical utility is constantly expanding, they have been best studied in complicated urinary tract infections, chronic osteomyelitis caused by gram-negative bacilli, bacterial gastrointestinal infections such as traveler's diarrhea and typhoid fever, and uncomplicated gonococcal infections and in the prophylaxis of bacterial infections in patients with neutropenia. These agents have the convenience of oral administration, favorable pharmacokinetic properties, and low toxicity profiles but should be used advisedly because indiscriminate use may result in the early emergence of resistance.

4-Quinolones↗

Piperacillin/tazobactam compared with ticarcillin/clavulanate in community-acquired bacterial lower respiratory tract infection.

The efficacy and safety of a new combination parenteral antibiotic, piperacillin/tazobactam, was compared with that of parenteral ticarcillin/clavulanate in the treatment of adult patients with community-acquired lower respiratory tract infections. A total of 299 patients were enrolled in this multicentre, double-blind, comparative study; 177 received piperacillin/tazobactam and 122 received ticarcillin/clavulanate. Of these, 119 met the evaluability criteria (69, piperacillin/tazobactam and 50, ticarcillin/clavulanate). The study drugs (piperacillin/tazobactam 3 g/375 mg or ticarcillin/clavulanate 3 g/100 mg) were given every 6 h by slow iv infusion for a minimum of 5 days. The favourable clinical response (cured and improved) rates of evaluable patients were 84% and 64% at endpoint (P < 0.01) for piperacillin/tazobactam and ticarcillin/clavulanate, respectively. The favourable bacteriological response at the early follow-up (eradicated and presumed eradicated) were 91% and 67% for piperacillin/tazobactam and ticarcillin/clavulanate, respectively (P < 0.01). At endpoint, 84% and 64%, respectively (P = 0.02) had a favourable response. The most common adverse experiences involved the gastrointestinal tract and occurred in 31.6% of the piperacillin/tazobactam group compared with 20.5% in the ticarcillin/clavulanate group (P = 0.02). These events were mild and generally did not affect therapy. Piperacillin/tazobactam appears to be more effective than ticarcillin/clavulanate in this patient population and is generally well tolerated.

Adolescent↗

Development of new antibiotic resistance in methicillin-resistant but not methicillin-susceptible Staphylococcus aureus.

The frequency of infections caused by multidrug-resistant Staphylococcus aureus continues to increase while the numbers of alternative therapeutic agents remain limited. To investigate the changing patterns of in-vitro susceptibility of S. aureus to 16 antibiotics, 190 clinical isolates from two different years were studied. The MICs of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains isolated in 1987 were compared with those of similar numbers of strains isolated in 1989. For MRSA > or = 90% of isolates from both years were resistant to clindamycin, gentamicin and erythromycin. These strains remained highly susceptible to vancomycin (100%), minocycline (90%) and rifampicin (100%). The greatest increase in resistance was observed for ofloxacin (2% in 1987 vs 62% in 1989); cross-resistance to all of the quinolones tested was demonstrated. MSSA strains remained susceptible to vancomycin (100%), minocycline (98%), rifampicin (100%), clindamycin (90%), gentamicin (90%) and ciprofloxacin (98%). It is concluded that methicillin susceptibility is a useful marker for selecting potential agents for the treatment of infections caused by S. aureus. A combination of minocycline and rifampicin may be a useful alternative to vancomycin for treating MRSA infections.

Drug Resistance, Microbial↗

Conservative management of cervical pregnancy with subsequent fertility.

The reported incidence of cervical pregnancies with subsequent fertility is extremely low. We report a case managed conservatively that allowed for future fertility, and ultimately the delivery of a viable infant at term. The conservative management and a review of the literature are discussed.

Adult↗

Neuroendocrine aberrations in women with functional hypothalamic amenorrhea.

To further elucidate the neuroendocrine regulation of anterior pituitary function in women with functional hypothalamic amenorrhea (FHA), we measured serum LH, FSH, cortisol, GH, PRL, TSH concentrations simultaneously at frequent intervals for 24 h in 10 women with FHA and in 10 normal women in the early follicular phase (NC). Using the same data, we separately analyzed the cortisol-PRL responses to meals in these women. In addition, the pituitary responses to the simultaneous administration of GnRH, CRH, GHRH, and TRH were assessed in 6 FHA and 6 normal women. The 24-h secretory pattern of each hormone except TSH was altered in the women with FHA. Compared to normal women, the women with FHA had a 53% reduction in LH pulse frequency (P less than 0.0001) and an increase in the mean LH interpulse interval (P less than 0.01); LH pulse amplitude was similar. The 24-h integrated LH and FSH concentrations were reduced 30% (P = 0.01) and 19% (P less than 0.05), respectively. The mean cortisol pulse frequency, amplitude, interpulse interval, and duration were similar in the two groups, but integrated 24-h cortisol secretion was 17% higher in the women with FHA (P less than 0.05). This increase was greatest from 0800-1600 h, but also was present from 2400-0800 h. Cortisol levels were similar in the two groups from 1600-2400 h, resulting in an amplified circadian excursion. In contrast, the 24-h serum PRL levels were markedly lower at all times (P less than 0.0001), the sleep-associated nocturnal elevation of PRL was proportionately greater (P less than 0.05), and serum GH levels were increased at night in the women with FHA (P less than 0.05). Although 24-h serum TSH levels were similar at all times, T3 (P less than 0.05) and T4 (P less than 0.01) levels were lower in the FHA women. The responses of serum cortisol to lunch (P less than 0.01) and dinner (P less than 0.05) and those of serum PRL to lunch (P less than 0.05) and dinner (P = 0.08) were blunted in the women with FHA. Pituitary hormone increments in response to the simultaneous iv administration of GnRH, CRH, GHRH, and TRH were similar in the two groups, except for a blunted PRL response to TRH in the women with FHA (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗