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Biomedical subjects

Lawrence A Cone

Publications and source records attributed to Lawrence A Cone.

At least 19 recordsLinked to original sources

Leptomeningeal carcinomatosis in a patient with metastatic prostate cancer: case report and literature review.

BACKGROUND: Leptomeningeal metastasis is discovered at autopsy in approximately 5% of patients with systemic cancer. Until recently with the introduction of magnetic resonance imaging (MRI), premorbid diagnosis was extremely difficult. In particular, initial spinal fluid cytology is diagnostic in less than 50% of autopsy-verified patients, although repeated spinal fluid examinations may increase the yield significantly. Leptomeningeal metastasis in metastatic prostate cancer has been reported in only 14 patients previously. CASE DESCRIPTION: We recently studied such a patient and were able to establish a correct diagnosis based solely on the MRI and the presence of an elevated cerebrospinal fluid (CSF) prostate-specific antigen (PSA). Only 3 previous patients with leptomeningeal prostate metastasis have undergone CSF PSA evaluations. CONCLUSION: We believe that, in such patients, the combination of MRI and CSF studies can overcome the lack of sensitivity of CSF cytology.

Aged↗

An early favorable outcome of streptococcal toxic shock syndrome may require a combination of antimicrobial and intravenous gamma globulin therapy together with activated protein C.

Streptococcal toxic shock syndrome (STSS) associated with a group A beta hemolytic streptococcal infection was described 18 y ago. Since then, although the pathophysiology of the syndrome has been clarified, mortality can be as high as 80%. A middle-aged female developed STSS associated with a group A streptococcal pneumonia. Laboratory studies confirmed respiratory and renal failure as well as disseminated intravascular coagulation with a striking reduction in endogenous procoagulants. The patient, probably due to her HLA DRB1*14 haplotype was unable to generate anti-streptococcal antibodies. She was treated with appropriate antimicrobial therapy together with intravenous gamma globulin and drotrecogin or activated protein C. Her response to this combined therapy was accompanied by a rapid resolution of the multiorgan failure and correction of the accompanying disseminated intravascular coagulation. This rapid response to treatment supports the hypohesis that several host factors including the immune response and loss of procoagulants determine the development and severity of the toxic shock syndromes. Further studies with this combined approach appear warranted.

Anti-Infective Agents↗

Staphylococcal septic synovitis of the sternoclavicular joint with retrosternal extension.

Bacterial arthritis of the sternoclavicular joint is an uncommon disorder caused by a variety of microorganisms. Both Gram-positive and Gram-negative bacteria have been identified as etiologies of an acute suppurative arthritis, whereas a few other bacteria such as mycobacteria and treponemes have been incriminated in chronic disease of the sternoclavicular joint. We recently treated a patient with staphylococcal synovitis of the sternoclavicular joint, which is the 24th recorded in the literature. His illness was complicated by a retrosternal abscess, soft tissue abscess of the chest, septic bursitis, and lumbosacral discitis. He recovered after 6 weeks of nafcillin therapy without any residual infection. Six previous patients with extension into the substernal space and mediastinum have been described. Staphylococcal infection of the sternoclavicular joint, although usually confined to the joint, can be associated with sepsis and metastatic abscess formation as well as substernal extension even in immunocompetent individuals.

Abscess↗

Q fever in the Southern California desert: epidemiology, clinical presentation and treatment.

Despite the absence of a natural reservoir for Q fever in the desert of Southern California, six cases have been identified during the past 32 years. During that period of time, two areas have been used by northern sheep ranchers from Idaho and Wyoming to import sheep to an area in the Coachella Valley through 1985. Thereafter, because of housing development, the sheep area was moved to Blythe along the Colorado River. All but two of these patients probably acquired infection by Coxiella burnetii by living or working in close proximity to these grazing areas but not directly involved with the sheep. The shift of infected patients from the Coachella Valley to Blythe (100 miles distant) seems to support that supposition. All patients with acute Q fever developed antibodies primarily to phase II antigen, whereas the only person with chronic Q fever developed phase I antibodies. All patients presented with granulomatous hepatitis. One also had a pulmonary infiltrate, and the single individual with chronic Q fever also had a mitral valve prosthesis, although echocardiography could not define endocarditis. All patients with acute infections responded to 3-5 weeks of therapy with doxycycline, whereas the patient with chronic disease failed 3 years of therapy with combination regimens. Further studies at the Eisenhower Medical Center on the prevalence of infection in Blythe, CA, and elsewhere are anticipated.

Adult↗

The serologic prevalence of Q fever (Coxiella burnetii) complement-fixing antibodies in the Peninsular bighorn sheep of Southern California.

Q fever is a rare illness in the Southern California desert. During the past 34 years only 6 patients have been diagnosed with the disease at the Eisenhower Medical Center, a referral center for much of the desert and surrounding mountains. In all but 2 instances, Q fever was identified in patients who have been in contact with imported domestic sheep who are brought to the desert to graze and lamb in the fall and winter. The sheep are sent back to Idaho, Wyoming, and Montana in the spring. With frequent infection by Coxiella burnetii established in domestic sheep, we elected to study the prevalence of complement fixing antibodies to Coxiella burnetii in native bighorn sheep who reside in the lower levels of the mountains surrounding the desert. From 1992 to 1999, of 268 serum samples drawn from male and female lambs and adult sheep, 27 tested positive (10%), which is strikingly low when compared with Dall sheep in Alaska (12 of 15), kangaroos, wild rabbits, and brown rats. Because changes have been made in Peninsular bighorn sheep habitat since the animals were listed as endangered in 1998, further follow-up in Q fever serology testing will be of interest.

Animals↗

Staphylococcus capitis endocarditis due to a transvenous endocardial pacemaker infection: case report and review of Staphylococcus capitis endocarditis.

OBJECTIVES: Newer microbiologic methods to determine the species of coagulase-negative staphylococci (CoNS) have evolved which have shown that most endocarditis due to CoNS is caused by Staphylococcus epidermidis, and far fewer by Staphylococcus warneri and Staphylococcus lugdunensis. METHODS: The recent opportunity to successfully treat a patient with methicillin-resistant Staphylococcus capitis endocarditis secondary to an infected transvenous pacemaker led to a review of the literature relating to S. capitis endocarditis. RESULTS: Thirteen previously recorded patients were identified. Twelve (86%) patients were male. Ten had endocarditis associated with a native valve, two with prosthetic valves and one with a transvenous pacemaker. Mortality was low in all 14 cases (including this case report) with only two deaths; one in a patient with a native valve and the other with a prosthetic valve. Four of the isolates were methicillin resistant but sensitive to vancomycin, which was used in the treatment of eight patients. Those patients with prosthetic cardiac devices appear to do better when the devices are surgically removed. CONCLUSIONS: CoNS as a cause of endocarditis appears to be increasing and the current ability to determine the species of these organisms should elicit the epidemiology, clinical characteristics and biomolecular mechanisms involved in the induction of valvular disease.

Adult↗

Fatal Bacillus cereus endocarditis masquerading as an anthrax-like infection in a patient with acute lymphoblastic leukemia: case report.

A 38-year-old male farm worker with relapsing acute lymphoblastic leukemia spontaneously developed an ulcerating ulcer on his anterior thigh which was surrounded by a non-tender area of erythema. Bacillus cereus was isolated from the ulcer and blood, and the patient received intravenous penicillin and vancomycin for one week. When sensitivity studies were returned he was treated with gatifloxacin orally. After two weeks of combined antimicrobial therapy and negative blood cultures, the patient received combination chemotherapy with vincristine, prednisone, doxorubicin and cyclophosphamide. He was hospitalized a day after completing chemotherapy with neutropenic sepsis due to B. cereus. He received similar antimicrobial therapy as previously, but died three days later. At autopsy, the patient was found to have acute mitral valve endocarditis and bilateral brain abscesses. This was the first case of B. cereus endocarditis reported in a patient with acute lymphoblastic leukemia.

Abscess↗

Diagnosis and treatment of Candida vertebral osteomyelitis: clinical experience with a short course therapy of amphotericin B lipid complex.

BACKGROUND: Musculoskeletal candidiasis occurs in some patients with candidemia resulting from organ infection, IV drug use, or indwelling central venous catheters. Diagnosis is often difficult because of vague symptomatology and a frequent afebrile course. CASE DESCRIPTION: Three patients with Candida vertebral osteomyelitis are presented. All followed the use of indwelling central venous access catheters and antimicrobial therapy between 6 months and 3 years earlier. In 2, fungemia with the same Candida spp. preceded the spondylodiskitis. These 3 patients bring to nearly 75 the number of reported individuals with what was once quite rare. Although IV amphotericin B doxycholate and fluconazole have usually been effective therapy over prolonged periods of time, we used liposomal amphotericin B to treat 2 of our 3 patients. Both received 5 mg/kg daily for 18-42 days that resulted in total disappearance of signs and symptoms. CONCLUSION: This relatively brief duration of therapy reduces treatment time and is cost-effective.

Aged↗

Clinical experience with drotrecogin alfa in treating gram-positive and -negative pathogens in patients with severe sepsis.

BACKGROUND: Newer concepts in the management of severe sepsis and, in particular, in the understanding of the relationship between proinflammatory and procoagulant activities during severe infection have led to the introduction of activated protein C (drotrecogin) into the therapeutic program. The combination of effective antimicrobial therapy, aggressive supportive care, and efforts to antagonize procoagulants and inhibitors of fibrinolysis was used in this study. METHODS: We treated 12 patients with severe sepsis using this combination of antimicrobial agents and drotrecogin. All patients presented with hypotension and organ failure and some with multiple organ failure. Infected patients were separated into those with gram-positive and those with gram-negative infections. RESULTS: In contrast to an expected mortality rate of nearly 40% in this group of patients, only 2 (9%) expired. Both deaths were due to infection by gram-negative organisms in patients with complicated abdominal infections and concurrent cancer. All patients with gram-positive organisms survived. CONCLUSION: Those patients with infections caused by gram-positive organisms seemed to have a better prognosis than those with gram-negative infections, perhaps because their illnesses are less complicated by local disease. Although our study is small, it suggests that activated protein C will have a significant beneficial effect on the future treatment of severe sepsis and can reduce the mortality rate significantly. Further improvement in survival rates will require more effective treatment of local disease and associated noninfectious ailments.

Adult↗

RANTES: a genetic risk marker for multiple sclerosis.

UNLABELLED: Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a beta-chemokine and has been detected in brain lesions of multiple sclerosis (MS) patients. Considering its potential role in MS, we screened two functional polymorphisms in the proximal promoter region of the RANTES in MS patients versus controls. METHODS: We examined 140 postmortem brain samples from subjects with a primary diagnosis of MS, and peripheral blood samples from 216 control subjects. The RANTES-28C/G and -403G/A promoter polymorphisms were examined. All subjects were non-Hispanic Caucasians. RESULTS: MS cases differed from controls showing a significant association with the 403G/A polymorphism (odds ratio, 2.359, [1.465-3.799]; P=0.0001), but not the -28C/G (P=NS) polymorphism. There was a significant association of the -28G allele with both early onset (P=0.031) and longer survival (P=0.006). CONCLUSION: There is a significant but complex association of the RANTES gene with MS.

Adult↗

Purpura fulminans due to Streptococcus pneumoniae sepsis following gastric bypass.

An older female underwent bariatric surgery which was followed by a significant weight loss and diarrhea, from which C. difficile was isolated just before her hospitalization. Less than 48 hours after admission, she became febrile, developed deep venous thrombosis of the leg and a pulmonary embolus. Blood cultures grew out Streptococcus pneumoniae and the patient developed purpura fulminans. There was convincing laboratory evidence for disseminated intravascular coagulation and a marked depletion of proteins C and S as well as antithrombin. Treatment with ceftriaxone and drotrecogin alfa together with parenteral nutrition led to disappearance of the pathogen and ultimate normalization of the anticoagulant factors. We believe that malabsorption of vitamin K dependent proteins C, S and antithrombin due to bariatric surgery predisposed the patient to purpura fulminans and disseminated intravascular coagulation.

Antithrombins↗

A multigene test for the risk of sporadic breast carcinoma.

BACKGROUND: Although the identification of the BRCA1 and BRCA2 genes have been of great interest, these genes account for less than 5% of all breast carcinoma cases. The remaining cases are sporadic. Reanalysis of a large twin study suggested that genetic factors may play a significant role in sporadic breast and other carcinomas. Sporadic breast carcinoma is polygenically inherited. Multiple genes are likely to have an additive effect, each gene accounting for a fraction of the variance. One factor that may have an impact on the development of hormonally responsive breast tumors is the duration of exposure of the breast to estrogen. Therefore, one of the demographic risk factors for breast carcinoma is an early age of onset of menarche. The current study was based on the hypothesis that genes that play a role in demographic risk factors may be breast carcinoma risk genes in their own right. The authors hypothesized that six genes relevant to the timing of the onset of menarche and related risk factors might be candidate genes for breast carcinoma. These were the leptin gene (LEP), the leptin receptor gene (LEPR), the catechol-0-methyltransferase gene (COMT), the dopamine D(2) receptor gene (DRD2), the estrogen 1 receptor gene (ESR1), and the androgen receptor gene (AR). METHODS: The authors examined 67 women with postmenopausal sporadic breast carcinoma and 145 gender and race-matched controls. RESULTS: Five of these genes accounted for a significant percent of the variance (r(2)) of breast carcinoma. The following r(2) and P values were calculated: LEP: 0.073, P < or = 0.0001; LEPR: 0.064, P < or = 0.0002; COMT: 0.073, P < or = 0.0001; AR: 0.040, P < or = 0.0035; and DRD2: 0.018, P < or = 0.05. When evaluated in a multivariate regression analysis, they accounted collectively for 24% of the variance of breast carcinoma (P < or = 0.0001). These genes accounted for 40% of the variance (P < or = 0.00001) in a subset of age-matched cases. Individual gene scores were added to form a breast carcinoma risk score (BCRS) that ranged from 0 to 17. When the BCRS was evaluated in a receiver operator characteristic plot, the area under the curve was 0.80 for the full set and 0.869 for the age-matched set. The relative breast carcinoma risk for the different BCRS scores ranged from 0.10 to 11.9. CONCLUSIONS: These results demonstrate a potentially powerful method of evaluating the additive effect of multiple breast carcinoma risk genes to form a potentially clinically useful assessment of women's risk for sporadic breast carcinoma.

Adult↗

Multiple cerebral abscesses because of Listeria monocytogenes: three case reports and a literature review of supratentorial listerial brain abscess(es).

BACKGROUND: Central nervous system involvement often follows bacteremia because of Listeria monocytogenes. Meningitis is clinically the most common manifestation, while brain abscess occurs in about 1% of patients. Brain abscess is usually solitary but in recent years, probably in part because of the availability of computerized tomography and magnetic resonance imaging, several reports have described two or more separate supratentorial abscesses. METHODS: We have described three patients with listerial brain abscesses and reviewed the North American and European literature of brain abscess(es) because of L. monocytogenes through December 2001. We have evaluated the role of underlying diseases and therapeutic immunosuppression on the development of solitary or greater than one brain abscess. RESULTS: In contrast to meningitis, where immunosuppression does not predispose either to disease incidence or to higher mortality, patients with solitary and particularly those with more than one supratentorial abscess usually are immunosuppressed either by disease or by therapy. Corticosteroids in particular are significant predisposing factors, especially in those patients with two or more brain abscesses. Mortality resulting from listerial brain abscess, whether solitary or multiple, is nearly three times higher than nonlisterial brain abscess, probably in part because of both underlying diseases and immunosuppressive therapy. CONCLUSIONS: Therapy with high-dose ampicillin in combination with gentamicin appear to be the drugs of choice, followed by trimethoprim/sufamethoxazole and vancomycin. In general, antimicrobial therapy appears to be satisfactory treatment without surgical intervention.

Adrenal Cortex Hormones↗

Delirium in the elderly resulting from azithromycin therapy.

BACKGROUND: Azithromycin, a semi-synthetic azalide antibiotic, is a macrolide that thus far has not shared the neuropsychiatric side effects of other macrolides such as erythromycin and clarithromycin. METHODS: We now report significant delirium associated with conventional dosing of azithromycin in two geriatric patients who were being treated for lower respiratory tract infection. RESULTS: The onset of delirium was apparent within 72 hours of initiating azithromycin therapy and lasted 48 to 72 hours after discontinuing treatment with the drug. CONCLUSIONS: In contrast to the adverse central nervous system symptoms associated with clarithromycin, those induced by azithromycin seem to take longer to resolve, perhaps based upon the longer elimination half-life of the latter antimicrobial, particularly in geriatric women.

Aged↗

Cellulitis and septic arthritis caused by Campylobacter fetus and Campylobacter jejuni: report of 2 cases and review of the literature.

Bacteremia caused by gram-negative bacteria occasionally causes soft tissue infections, including cellulitis and septic arthritis. We describe 1 patient each with Campylobacter fetus cellulitis and septic arthritis and review the world literature with regard to C. fetus and C. jejuni infections at these sites. Altogether, 14 patients with cellulitis (12 due to C. fetus and 2 due to C. jejuni) and 20 patients with septic arthritis (15 due to C. fetus and 4 caused by C. jejuni) have been described. Most infections, particularly those causing cellulitis, are found in elderly men with underlying systemic disease. Most patients are febrile but less than half manifest a leukocytosis. There were only 3 deaths in this series of 33 patients. The newer macrolides, including azithromycin and clarithromycin, are considered the drugs of choice, particularly with C. jejuni, while soft tissue infections caused by C. fetus respond nicely to many beta-lactams, particularly to cephalosporins and carbapenems, as well as to macrolides and quinolones.

Journal Article↗

Actinomyces odontolyticus bacteremia.

We describe two immunosuppressed female patients with fever and Actinomyces odontolyticus bacteremia, a combination documented once previously in an immunocompetent male patient. The patients were treated with doxycycline and clindamycin; these drugs, with beta-lactams, are effective treatment for A. odontolyticus infections.

Actinomyces↗