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Biomedical subjects

F Anwar

Publications and source records attributed to F Anwar.

11 recordsLinked to original sources
PubMed2000

Retinoblastoma expression in thyroid neoplasms.

Retinoblastoma (Rb) mutation in thyroid neoplasia has been identified in a few molecular studies; however, the utility of Rb immunohistochemistry in distinguishing benign and malignant thyroid lesions has not been documented in formalin-fixed, paraffin-embedded tissues. The present study investigated Rb immunohistochemistry in a series of 111 formalin-fixed, paraffin-embedded benign and malignant thyroid lesions. All of the major histologic subtypes were included to detect any heterogeneity in Rb-1 expression that might influence the diagnostic utility of this technique or further elucidate the pathogenesis of thyroid neoplasia among the categories. Altogether, 34 follicular adenomas, 9 follicular carcinomas, 7 Hürthle cell adenomas, 5 Hürthle cell carcinomas, 23 papillary carcinomas (8 of which were follicular variants), 4 insular carcinomas, 4 anaplastic carcinomas, 6 medullary carcinomas, and 19 nodular goiters were analyzed. Avidinbiotin immunohistochemistry was performed using the Dako Rb-1 clone. Pronase digestion was introduced into the epitope retrieval protocol to eliminate false-positive cytoplasmic stainig. Nuclear immunoreactivity was assessed as positive if 10% or more of thyroid epithelial nuclei stained positively, and conversely as negative. The majority of benign non-Hürthle thyroid lesions, whether hyperplastic or neoplastic, retained Rb nuclear immunopositivity in most cells (51 of 53 cases [96%]). Conversely, malignant thyroid neoplasms lacked Rb immunoreactivity in the majority (42 of 51 cases [82%]), including all papillary carcinomas (23 of 23) and almost all follicular carcinomas (8 of 9 [89%]). Virtually all Hürthle cell neoplasms were negative (11 of 12 [92%]), whether benign or malignant. In conclusion, Rb immunohistochemistry can aid in the distinction between benign and malignant thyroid lesions in conjunction with morphology. This seems to be most applicable to the often problematic differentiation between follicular adenoma and the follicular variant of papillary carcinoma (P < .0001; sensitivity and specificity, 100%) or minimally invasive follicular carcinoma (P = .0007; sensitivity, 89%; specificity, 100%).

Adenoma↗
PubMed1999

Apoptosis, Bcl-2, and proliferating cell nuclear antigen in the failing human heart: observations made after implantation of left ventricular assist device.

BACKGROUND: Heart failure is characterized by progressive left ventricular remodeling, a complex process that results from cell growth and cell death. The quantitative contribution of apoptotic cells toward left ventricular remodeling has varied widely in tissue removed from cardiomyopathic hearts. Apoptosis has been responsive to angiotensin-converting enzyme inhibition in experimental heart failure, but the dynamics and responsiveness to chronic left ventricular unloading have not been studied. METHODS AND RESULTS: We studied 8 patients with severe heart failure before and after chronic left ventricular unloading with a left ventricular assist device (LVAD). Tissue from the left ventricular apex removed at the time of LVAD implantation was examined for apoptosis using the technique of terminal deoxynucleotidyl transferase deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) in 10 patients. These same hearts explanted at the time of cardiac transplantation were then examined for apoptosis after patients had been on the LVAD for 99 +/- 20 (SEM) days. An additional 10 patients with equally severe heart failure who underwent heart transplantation without the use of an LVAD served as controls. Eight hearts obtained at autopsy approximately 6 hours after death from patients who died of non-cardiovascular disease causes served as non-heart failure controls. Additionally, 6 hearts were examined by immunohistochemistry for the antiapoptotic protein, Bcl-2, and for the repair and/or proliferation marker, proliferating cell nuclear antigen (PCNA), before and after LVAD. Apoptosis was not detected in the tissue sections from the hearts of 8 patients at the time of LVAD implantation. Only 1 of these patients had limited apoptosis (< 1 apoptotic cell/1,000 myocytes) after LVAD insertion. Three of 10 patients with severe heart failure who did not receive an LVAD but underwent transplantation showed limited apoptosis (< 1 apoptotic cell/1,000 myocytes). Likewise, none of the control hearts from patients who died of noncardiovascular disease manifested apoptosis. Six of 6 patients overexpressed Bcl-2 at the time of LVAD insertion. In all these patients, Bcl-2 returned to negligible levels after chronic unloading of the heart. Likewise, PCNA was abundantly expressed in 5 of 6 failing hearts at the time of LVAD implantation and was reduced in 4 of 5 hearts after chronic unloading by LVAD. CONCLUSION: Apoptosis is a rare or inconsistent finding in the failing human heart. Overexpression of such indicators of cellular stress and DNA replication and/or repair as Bcl-2 and PNCA in heart failure may be altered by optimizing left ventricular loading conditions by such mechanical devices as the LVAD.

Adult↗
PubMed1999

Are there cytopathic features associated with cytomegalovirus infection predictive of resistance to antiviral therapy?

Recent awareness of the broader spectrum of morphologic changes induced by cytomegalovirus (CMV) infection prompted us to investigate whether the concurrent introduction of effective antiviral therapy is in some way related to the appearance of atypical cytopathic features. These changes may be easily misinterpreted on histologic examination as reactive or degenerative. In addition, since resistant strain to antiviral therapy has emerged and its demonstration is a laborious process performed in highly specialized laboratories, it is important to determine if resistance to antiviral drugs can be predicted from the microscopic examination of infected tissues. The population consisted of seven immunosuppressed patients with documented CMV infection from which 18 tissue samples were obtained at autopsy or endoscopically. Antiviral susceptibility to ganciclovir was determined by plaque reduction assay and/or a DNA-DNA hybridization method. Eleven tissue specimens from patients harboring resistant strains were compared with seven specimens from patients infected with sensitive strains. Cytopathic changes were classified as typical or atypical according to previously published criteria. Of the 18 biopsy specimens, the cytopathic changes were distributed as follows: typical 1, typical and atypical 5, and atypical 12. Atypical inclusions were found in 10 of 11 and 7 of 7 sensitive and resistant cases, respectively. In conclusion, there are no specific morphologic features in CMV-infected tissues of patients with infections caused by ganciclovir resistant strains.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Cytomegalovirus UL97 and glycoprotein B (gB) sequences in tissues from immunocompromised patients with ganciclovir-resistant virus infection.

The pathogenesis of ganciclovir-resistant cytomegalovirus (CMV) was investigated by analysing UL97 and gB sequences in tissues obtained from 4 immunocompromised patients with infections caused by ganalciclovir-resistant virus. UL97 and gB sequences were obtained by automated sequencing of CMV DNA amplified from lysates prepared from deparaffinized tissue sections. Patient 1 contained wild-type UL97 and gB3 sequences. Patient 2 harboured genetically distinct viruses in his lung: one with a ganciclovir-resistance UL97 mutation and a gB3 genotype, and another without UL97 mutations and a gB1 genotype. In patient 3, a ganciclovir-resistant UL97 mutant virus with a gB1 genotype was cultured from the lung, whereas the CMV in the brain did not contain mutations and its genotype was gB2. In patient 4, ganciclovir-resistance UL97 sequences were found in oesophageal tissue prior to the isolation of a ganciclovir-resistant CMV from the blood. All viruses in this patient had a gB3 genotype. CMV containing ganciclovir-resistance UL97 mutations may cause end-organ disease in immunocompromised individuals. In these subjects, CMV circulating in the blood may have similar or different UL97 and gB genotypes than the virus causing end-organ disease.

Antiviral Agents↗
PubMed1995

Factors determining hemoglobin carbamylation in renal failure.

Carbamylated hemoglobin (carhb) is formed by the reaction of hemoglobin with cyanate, a product of in vivo urea dissociation. It is found in high levels in patients with renal failure and may be useful in their clinical evaluation. Accordingly, we measured carhb by HPLC after acid hydrolysis in 73 patients with renal failure and 11 controls. Mean carhb levels (expressed as micrograms valine hydantoin/g Hb), were highest in chronic renal failure (CRF, 146 +/- 13), intermediate in end-stage renal disease on hemodialysis (ESRD, 106 +/- 7), and lowest in acute renal failure (ARF, 80 +/- 12) when compared to normal subjects (27 +/- 2). In all patients carhb was significantly correlated with BUN but not with creatinine, bicarbonate, or phosphate. For any level of BUN above 80 mg/dl, carhb was substantially higher in CRF than in ARF. Predialysis BUN and urea reduction ratio (URR) were significant predictors of carhb in ESRD. To investigate the effect of time of exposure and BUN level on the rate of carbamylation of hemoglobin, blood from normal subjects and dialysis patients was incubated in vitro with urea equivalent to BUN levels of 50, 100, 150, and 200 mg/dl and assayed for carhb at 0, 5, 9, and 14 days. Carhb increased linearly over the first nine days of urea exposure and leveled off thereafter. The rate of carbamylation increased as BUN increased and was significantly higher in hemoglobin from dialysis patients than from normal subjects. These results show that the higher the level of carhb at baseline, the higher the rate of carbamylation upon exposure to increasing urea concentrations. We conclude that carhb formation is dependent on urea concentration and length of exposure to urea. The rate of carhb formation for a given urea concentration is greater in hemoglobin already carbamylated, and this may explain why carhb is higher in CRF than in ARF at BUN levels greater than 80 mg/dl. Carhb may thus be a useful index of the duration and degree of exposure to high blood urea levels in patients with renal failure, and may potentially serve as an index of the adequacy of dialysis.

Acute Kidney Injury↗
PubMed1991

Antimicrobial resistance of pneumococci in children with acute lower respiratory tract infection in Pakistan.

87 strains of Streptococcus pneumoniae isolated during three winter seasons (1986-89) from the blood of children with acute lower respiratory tract infection (ALRI) in Pakistan were serotyped and tested for susceptibility to a range of antimicrobial agents. 97% of isolates were resistant to at least one antimicrobial drug. 62% had decreased susceptibility to co-trimoxazole (trimethoprim/sulphamethoxazole) (31% were fully resistant) and 39% were resistant to chloramphenicol. All isolates were susceptible to erythromycin, cefaclor, cephalothin, ceftriaxone, cefuroxime, rifampicin, vancomycin, and clindamycin. 29% of isolates were neither vaccine types nor vaccine-related types. Serotype distribution and antimicrobial susceptibility varied significantly during the three winter seasons. No single serotype was found in all three winters. The findings highlight the need for surveillance of antimicrobial resistance and serotype distribution of S pneumoniae in developing countries as a guide both to the choice of agent for treatment of pneumococcal infections, especially ALRI, and to the formulation of new pneumococcal conjugate vaccines for use in young children.

Child, Preschool↗
PubMed1991

Seroepidemiology of toxoplasma gondii infection in young school children in Islamabad.

Sera, from 270 school children (age 13 to 20 years) residing in suburbs of Islamabad, were investigated for the presence of toxoplasma gondii, IgG antibodies using the enzyme linked immunosorbent assay (ELISA). The overall prevalence was 17.4%. There was no significant difference between the two sexes. Since a positive test result for IgG antibodies at any level does not eliminate the possibility of a current infection, the toxoplasma IgG antibody positive children were further tested for the presence of toxoplasma IgM antibodies by the same technique. An acute infection was indicated in 12.7% (6/47) IgG positive children. This study shows that toxoplasmosis is prevalent in adolescence in Islamabad. The presence of cats and the degree of soil contact appeared compatible with hypothesis of transmission by oocysts. Poor sanitary habits and conditions and water shortage in schools may cause parasitic infection through contact between the children. An improvement in general hygienic conditions is important in reducing the rate of transmission by oocysts. Further studies are needed to assess the possible age of exposure to this parasite in the paediatric group.

Adolescent↗
PubMed1989

Clonal analysis of Hemophilus influenzae isolated from children from Pakistan with lower respiratory tract infections.

The clonal diversity of 105 Hemophilus isolates from the blood of children with lower respiratory tract infection in Pakistan was analyzed. Ten isolates were identified as H. parainfluenzae and 95 as H. influenzae. Of the H. influenzae isolates, 61 (64%) were serotype b and 34 (36%) were nontypable; 95% of the type b isolates were members of a single clonal group (as defined by multilocus enzyme electrophoresis, SDS-PAGE outer membrane protein profile, and biotype). This clone is rarely observed among type b strains recovered from patients with invasive type b disease in the USA or Europe. The nontypable isolates in Islamabad also were clonally restricted: 9 clonal groups were found among 34 isolates, with just 5 clonal groups accounting for most (82%) of the strains. Children infected with type b strains were hospitalized more often than those with nontypable H. influenzae disease (64% vs. 41%, P = .06), but no other clinical or demographic features distinguished children infected by type b and nontypable strains.

Bacterial Outer Membrane Proteins↗
PubMed1979

Kinaesthetic movement after-effects in children with Down's syndrome.

In order to assess the liability of proprioceptive information, an experiment on kinaesthetic after-effects was carried out. Matched groups of severely subnormal and Down's syndrome subjects were compared with normal children of either the same chronological or the same mental age. No difference was found between the normal and the severely subnormal children, but the magnitude of the after-effect measures in Down's syndrome children suggests that asymmetrical pointing produced kinaesthetic after-effects which disrupted these subjects' total frame of spatial reference.

Adolescent↗
PubMedDate not supplied

Diagnoses of acute lower respiratory tract infections in children in Rawalpindi and Islamabad, Pakistan.

A hospital-based inpatient and outpatient study of 1,492 cases of acute lower respiratory tract infection (ALRI) was conducted from November 1986 to March 1988 in two hospitals in Rawalpindi and Islamabad, Pakistan. Specimens of nasopharyngeal aspirate were processed for viral studies in all cases; blood cultures were performed in 1,331 cases; and urine was obtained for detection of bacterial antigen in 378 cases, but 227 of these samples had bacterial contamination and were discarded. Respiratory syncytial virus was identified in 33% of cases, and Haemophilus influenzae and Streptococcus pneumoniae were identified in 9.6% and 9.9% of cases, respectively. Nonencapsulated H. influenzae accounted for 32% of the Haemophilus isolates, and type b was the only encapsulated H. influenzae strain identified. Of the S. pneumoniae serotypes isolated, 31% are not included in the currently available polyvalent pneumococcal vaccine. No clinical characteristic was demonstrated to be a reliable indicator for bacterial ALRI.

Acute Disease↗