Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although influenza vaccination is recommended for individuals with HIV infection, there are no data indicating an increased incidence or severity of influenza in this population. We sought to describe the clinical manifestations and morbidity of influenza in HIV-infected patients. All cases of influenza occurring in HIV-infected individuals over 3 years at a large county hospital were reviewed. Forty-three cases of influenza were diagnosed. Most patients presented with typical signs and symptoms of influenza, including cough (90%), myalgias (64%), and fever (52%). Sore throat and headache occurred in less than half of patients. The mean CD4 cell count and HIV viral load in patients with influenza was 340 cells/mm(3) and 3.34 log copies/ml, respectively. No significant differences in CD4 counts or viral loads were noted in patients with pneumonia (n=7) compared with patients without pneumonia (n=36), P>0.5. Six patients were hospitalized. One patient each had encephalitis and renal failure, although the relationship to influenza was not clear. No new or unusual clinical manifestations were observed. The rate of pulmonary complications was similar to other studies in HIV-negative patients; however, the hospitalization rate was higher than commonly seen in HIV-negative individuals.
Int J STD AIDS 2001 Oct
PMID:Clinical manifestations of influenza in HIV-infected individuals. 1156 31

Over the past 20 years, combined treatment with radiotherapy and second-generation chemotherapy drugs was extensively studied in patients with locally advanced NSCLC and became the standard over radiotherapy alone in patients with good performance status. Radiosensitizing properties of cisplatin have been identified in the laboratory. Close temporal administration of cisplatin and radiation is mandatory for enhanced antitumor efficacy, but results in significant toxicity to normal tissues. Early clinical studies demonstrated that the concurrent administration of cisplatin during STD-RT was feasible, with acceptable esophageal toxicity, and had the potential of significantly improving locoregional control. Carboplatin administered concurrently with accelerated HFX-RT was responsible for a higher rate of esophageal toxicity. Further improvement in survival also requires an effective treatment of micro-metastatic disease through full-dose delivery of cytotoxic drugs and the addition of at least one more active drug in conjunction with cisplatin and radiotherapy to further improve locoregional control of the disease. In most clinical studies, etoposide was the second drug of choice because of its own radiosensitizing properties and possible synergy with cisplatin. In numerous phase II studies, concurrent radiotherapy and PE resulted in reproducible results in terms of local control (30%-40%), median survival (15-18 months), survival at 2 years (35%-40%), and survival at 5 years (25%-30%). In phase III studies, these results were shown to be superior to radiotherapy alone and to induction chemotherapy followed by STD-RT. The question of the potential benefit of HFX-RT combined with PE has been addressed in phase II and III studies. At this time, there is no firm evidence that concurrent chemotherapy with HFX-RT is superior to concurrent chemotherapy with STD-RT in terms of local control and survival. Only a significant benefit in terms of local control or survival would justify the significant increase of esophageal toxicity observed with HFX-RT, which remains the main limiting factor of concurrent chemoradiotherapy with PE. Studies on postinduction surgery after concurrent chemoradiotherapy have been of major interest, demonstrating that a complete pathologic response rate of 25% to 30% could be achieved with a relatively low dose of radiation (45 Gy) and that downstaging was a major determinant for improved long-term survival. Long-term survival after trimodality treatment, however, does not appear to be significantly different from what can be achieved with concurrent chemoradiotherapy alone in phase II studies. Whether postinduction surgery is beneficial to patients with histologically proved stage III (N2) and stage IIIB patients was the question addressed in a large, recently completed phase III intergroup trial and of which the results are eagerly awaited. Over the past 10 years, further progress in radiation technology has been accomplished through three-dimensional treatment planning, multileaf collimators, and electronic portal imaging devices, leading to high-precision conformal radiotherapy and dose escalation and (it is hoped) to improved local control. Intensity-modulated radiotherapy and respiratory gating remain to be evaluated. Accurate delineation of critical organs and pretreatment analysis of toxicity-predicting factors allow for better protection of normal intrathoracic tissues such as lung and esophagus and, it is hoped, will lead to a significant reduction in the incidence of radiation esophagitis and pneumonitis. Third-generation drugs such as taxanes, vinorelbine, and gemcitabine have demonstrated high response rates in NSCLC patients with favorable toxicity profiles. These drugs have also shown major radiosensitizing properties in the laboratory and in the clinical setting, often leading, however, to excessive radiosensitization and unacceptable normal tissue toxicities when administered at full dose concurrently with radiotherapy. Weekly administration of these drugs at reduced doses during a full course of conformational radiotherapy up to 70 Gy or more, however, resulted in encouraging results in several phase II studies, with median survival in excess of 20 months and 2- and 3-year survival rates near 50% and 40%, respectively. The respective benefits of either induction or consolidation full-dose chemotherapy with these drugs, before or after concurrent chemoradiotherapy with second- or third-generation chemotherapy, are presently being evaluated in phase III studies. As a result of improved survival and enhanced local control, most of these studies show a significant increase in the incidence of brain metastases. Because the brain is often the first site of relapse after concurrent chemoradiotherapy with or without surgery, the issue of prophylactic cranial irradiation is currently being addressed in a phase III trial.
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PMID:Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data. 1500 80

The purposes of this study were to measure incidence and determine risk factors associated with opportunistic infections (OIs) and mortality among an HIV-infected cohort in Nairobi, Kenya. Three hundred and eighty-one seropositive ambulatory adults in Nairobi, Kenya were followed from 1997 to 2000 with participants visiting the clinic every two months and when acutely ill. Acute bronchitis was the most frequent diagnosis, followed by sexually transmitted infections, candida vaginitis (among women), fever, diarrhoea, pneumonia, HIV-associated skin rash, oral candidiasis and urinary tract infection. Associations between the frequency of these diagnoses including survival and sociodemographic factors and initial CD4 count were assessed. A CD4 count <200 cells/mL at recruitment was strongly associated with decreased survival (adjusted odds ratio=3.0, 95% confidence interval 1.7-5.1). These findings may help to target high-risk populations and guide OI prevention and treatment strategies including decisions regarding initiation of antiretroviral therapy in sub-Saharan Africa.
Int J STD AIDS 2004 Feb
PMID:Mortality and burden of disease in a cohort of HIV-seropositive adults in Nairobi, Kenya. 1500 75

Spondylothoracic dysplasia (STD, MIM#277300) is an autosomal recessive disorder with high prevalence in the Puerto Rican population. It is generally regarded as a lethal condition. Since Jarcho and Levin described it in 1938, it has been referred to as spondylocostal dysplasia, costovertebral dysplasia, Jarcho-Levin syndrome and STD. We have prospectively characterized 27 patients with STD by detailed physical examination, pedigree analysis, thoracic CT scans, and pulmonary function tests (PFTs). Diagnoses were established using spinal radiographs and 3-D reconstructive CT scans to demonstrate fusion of the ribs at the costo-vertebral junction with a fan-like (crab-like) configuration of the thorax. Vertebral segmentation and formation defects were seen throughout the spine with a decrease in the number of vertebral bodies. Characteristic vertebral shape consisted of a decrease in antero-posterior diameter and an increase in lateral length, giving the vertebra a sickle shape. Eight out of 18 prospectively follow patients died within the first 6 months of life, a 44% mortality rate. Cause of death was respiratory insufficiency secondary to pneumonia and pulmonary restriction. This is an important finding since the vast majority of STD syndrome patients cited in the medical literature have died in the newborn and early childhood periods. Age of the remaining patients ranged from 4 months to 47 years. This represents the largest collection of patients with STD reported and it has allowed us to determine a detailed phenotype. Given 56% survival at 6 months, we show that STD is not a lethal syndrome.
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PMID:Phenotype characterization and natural history of spondylothoracic dysplasia syndrome: a series of 27 new cases. 1521 2

An HIV-1-infected adult presented with a short history of dyspnoea, productive cough and myalgia with fever. Shortly after presentation, he developed the abrupt onset of high-volume watery diarrhoea: stool culture grew Shigella sonnei. At the same time, he became hypoxaemic, and thoracic imaging showed bilateral lower lobe consolidation/collapse. Culture of sputum and blood was negative. The patient recovered with fluid resuscitation and ciprofloxacin monotherapy. This is the first reported case of pneumonia complicating S. sonnei dysentery in an HIV-infected adult.
Int J STD AIDS 2005 Nov
PMID:Pneumonia complicating Shigella sonnei dysentery in an HIV-infected adult male. 1630 74

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by a failure to generate immunoglobulins of all isotypes due to the absence of mature B cells and plasma cells, secondary to mutations in the Bruton's tyrosine kinase (Btk) gene. We report six patients with XLA, confirmed by mutation analysis, from northern Thailand. The mean age of onset was 2.5 years and the mean age at diagnosis was 7.3 years. All patients had a history of otitis media, pneumonia and arthritis at the time of diagnosis, five patients had developed bronchiectasis and 3 patients septicemia. Other infections reported included sinusitis (5/6), pericarditis (1/6), meningitis (1/6) and pyoderma (1/6). Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus were isolated on multiple occasions. One patient died of sepsis at the age of 16 years. These observations demonstrate that early diagnosis and treatment can improve prognosis and quality of life.
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PMID:X-linked agammaglobulinemia in northern Thailand. 1691 89

X-linked agammaglobulinemia is caused by mutations in the human BTK gene, leading to recurrent pyogenic infections. We describe four novel and three known BTK-mutations in seven patients from seven (six Thai and one Burmese) families. All but one were sporadic cases. Patients 1 and 2 had recurrent mutations in exon 10 (R288W) and exon 17 (R562W), respectively. Patient 3, a previously healthy individual who presented with pseudomonas sepsis with ecthyma gangrenosum had a known mutation in exon 17 (1749delT), leading to frameshift effect (F583fsX586). Patient 4 manifested with sepsis and concurrent acute appendicitis and pneumonia. He had a mutation, IVS8 + 1G > A, which led to an insertion of intron 8 into the transcripts. In Patient 5, a novel change in exon 7, c.588G > C, initially presumed Q196H, was found to cause a leaky splicing mutation, resulting in three distinct transcripts containing 17, 108, and 190 bp of the 5'-terminal of intron 7, which led to truncated peptides consisting of 203 and 211 amino acid residues (or Q196fsX204 and Q196fsX212, respectively). Patient 6 had a mutation in exon 14 (W421X), while patient 7 had a newly defined large deletion of exons 6-9. All of the mothers tested were mutation carriers. Transcript analysis in three mothers who were heterozygous for frameshift mutations revealed a minimal amount of aberrant transcripts, while their affected children had full expression of the mutant alleles, suggesting rapid degradation due to nonsense-mediated mRNA decay in the mothers. This is the first report of mutations of BTK from Thailand.
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PMID:Four novel and three recurrent mutations of the BTK gene and pathogenic effects of putative splice mutations. 1695 17

An HIV-infected man became increasingly breathless and cyanosed while receiving clindamycin and primaquine treatment for Pneumocystis jirovecii pneumonia. He was found to have 11.4% methaemoglobinaemia and recovered with conservative management.
Int J STD AIDS 2007 Aug
PMID:Methaemoglobinaemia causing progressive dyspnoea and cyanosis during treatment of Pneumocystis jirovecii pneumonia. 1768 26

We report a case of X-linked agammaglobulinemia who presented with bronchiectasis. The patient had suffered pneumonia about every five years since childhood until he presented to our hospital at age 34 years old. CT showed bronchiectasis predominantly in the right middle lobe, lingula, and lower lobes. Administration of antibiotics resulted in symptomatic relief. Episodes of recurrent pulmonary infection and bronchiectasis indicated congenital immunodeficiency disorder. Investigation of lymphocyte subsets and serum immunoglobulin values showed remarkable reduction of B cells, IgG 772 mg/dl, IgA 216 mg/dl, and IgM 29 mg/dl. Flow cytometric assessment combined with genetic analysis was performed, and the results showed decreased expression of monocyte Bruton's tyrosine kinase (BTK) and missense mutation of Btk gene. We diagnosed X-linked agammaglobulinemia. IgG remained above 600 mg/dl in this case, we have not administered immunoglobulin after discharge. He suffered from pneumonia in 2004 and 2006 and bronchiectasis has progressed. In this report, we present a case including CT findings over a period of 8 years.
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PMID:[Long-term CT findings of X-linked agammaglobulinemia with bronchiectasis diagnosed in an adult]. 1851 99

This study reviews the deaths and autopsies carried out over 23 years, 1983-2005, in a British Infection Unit in HIV patients. Of 115 HIV patients known to have died, we obtained data on 93%. Of this 80% were male, median age 38 (25-68) years; 83% were Caucasian; 12% Black African. Major risk factors were men who have sex with men, 52%; heterosexual in Africa, 17%; and injecting drug use, 8%. The commonest diagnosis pre- and post-autopsy diagnosis was pneumonia. Changes in diagnoses in the 38% who underwent autopsy were high (we requested autopsy in 50%). Primary diagnosis changed in 70%, and 36% of all opportunistic infections were missed. This included six of nine cytomegalovirus, all tuberculosis and 75% of Kaposi's sarcoma. Lymphoma was overdiagnosed. Thus, despite excellent resources, the majority of primary diagnoses were wrong, suggesting inadequacy of current diagnostics. To improve these and improve both epidemiological data and future management autopsy should be considered for all deaths.
Int J STD AIDS 2009 Feb
PMID:Autopsies in HIV: still identifying missed diagnoses. 1918 52


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