Role of Franzen needle aspiration biopsy in carcinoma of the prostate.

A retrospective study is reported of all Franzen fine-needle aspiration cytology undertaken at Southmead Hospital between January 1978 and December 1981. A total of 1043 aspirates were examined from 753 patients. The diagnosis of carcinoma of the prostate was missed in 2 patients. Twenty-one patients with cytologically-proven carcinoma in histologically-benign prostates were detected, and the role of the Franzen needle in the diagnosis of early prostatic cancer is discussed. Of the 218 patients proceeding to prostatectomy, there were 91 patients with carcinoma and in 65 (72%) the cytological and histological grading was identical. A significant disparity occurred in 8 cases and the reasons are discussed.     

Optimization of epoetin therapy with intravenous iron therapy in hemodialysis patients

Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease (ESRD) patients. Functional iron deficiency occurs with serum ferritin >500 ng/ml and/or transferrin saturation (TSAT) of 20 to 30%. This study examines the effects of a maintenance intravenous iron dextran (ivID) protocol that increased TSAT in ESRD hemodialysis patients from conventional levels of 20 to 30% (control group) to those of 30 to 50% (study group) for a period of 6 mo. Forty-two patients receiving chronic hemodialysis completed a 16- to 20-wk run-in period, during which maintenance ivID and rhEPO were administered in amounts to achieve average TSAT of 20 to 30% and baseline levels of hemoglobin of 9.5 to 12.0 g/dl. After the run-in period, 19 patients randomized to the control group received ivID doses of 25 to 150 mg/wk for 6 mo. Twenty-three patients randomized to the study group received four to six loading doses of ivID, 100 mg each, over a 2-wk period to achieve a TSAT >30% followed by 25 to 150 mg weekly to maintain TSAT between 30 and 50% for 6 mo. Both regimens were effective in maintaining targeted hemoglobin levels. Fifteen patients in the control group and 17 patients in the study group finished the study in which the primary outcome parameter by intention to treat analysis was the rhEPO dose needed to maintain prestudy hemoglobin levels. Maintenance ivID requirements in the study group increased from 176 to 501 mg/mo and were associated with a progressive increase in serum ferritin to 658 ng/ml. Epoetin dose requirements for the study group decreased by the third month and remained 40% lower than for the control group, resulting in an overall cost savings in managing the anemia. Secondary indicators of iron-deficient erythropoiesis were also assessed. Zinc protoporphyrin did not change in either group. Reticulocyte hemoglobin content increased only in the study group from 28.5 to 30.1 pg. It is concluded that maintenance of TSAT between 30 and 50% reduces rhEPO requirements significantly over a 6-mo period.     

Profile of hospital admissions following acute poisoning--experiences from a major teaching hospital in south India

This study was conducted to determine the incidence of hospital admissions following acute poisoning, nature of agents involved and change in pattern of poisoning over a 5-year period. Data from hospital records of all admissions to emergency department following acute poisoning collected prospectively were analysed for the period January 1993 to January 1998. A steady increase in deliberate poisoning using pesticides, particularly among young adults, was noted. Kerosene (paraffin) was the commonest poison in children and plant poisons were also common. There were 52 deaths (3.3%) among the 1584 admissions. The majority of deaths were due to pesticides. Poisoning and mortality followed ingestion of readily-available and commonly used agents. Measures to increase public education, counselling and awareness could prevent a number of these admissions.     

Jordans’ anomaly

A case of Jordans’ Anomaly of leucocytes is reported in a young boy with congenital ichthyosis and hepatosplenomegaly. Cytoplasmic vacuoles were seen in granulocytes, monocytes and lymphocytes of the patient and his father. Serum triglyceride was found elevated in the child but not in the father. Ultrasonogram of the patient’s liver showed features suggestive of fatty change, thus pointing to a possible abnormality of systemic triglyceride storage.     

The transition to medication system performance indicators

Economic and competitive pressures in the health care market are causing hospitals and other health care providers to seek more effective ways to improve the quality of care and to decrease costs. Integrating total quality management and continuous quality improvement techniques into traditional drug use evaluation methodology allows for the development of critical performance indicators. These indicators integrate the selection, use, delivery methods, and outcomes of drug therapy with other operational therapeutic modalities. The article describes the development of medication system performance indicators using heparin dosing as a model.     

Development and evaluation of a multiplex PCR for differentiation of foot-and-mouth disease virus strains native to India

A multiplex PCR (mPCR) for the differentiation of Indian FMDV serotypes, O, A, Asia 1 and C was developed and evaluated on 142 clinical and 39 cell culture samples. On the latter samples both the tests worked well with 100% efficiency, whereas on clinical samples mPCR had better efficiency than ELISA. The test was found to be specific for FMDV. The detection limit of the assay was varied among the serotypes; it was most sensitive on types A and Asia 1 and least sensitive on type C. The mPCR clearly identified the serotype and in some cases detected dual infections. The test is sensitive and reliable and can be used for serotyping of ELISA negative samples.     

Role for cell density in antifungal drug resistance in Candida albicans biofilms

Biofilms of Candida albicans are less susceptible to many antifungal drugs than are planktonic yeast cells. We investigated the contribution of cell density to biofilm phenotypic resistance. Planktonic yeast cells in RPMI 1640 were susceptible to azole-class drugs, amphotericin B, and caspofungin at 1 x 10(3) cells/ml (standard conditions) using the XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt] assay. As reported by others, as the cell concentration increased to 1 x 10(8) cells/ml, resistance was observed with 10- to 20-fold-greater MICs. Biofilms that formed in microtiter plate wells, like high-density planktonic organisms, were resistant to drugs. When biofilms were resuspended before testing, phenotypic resistance remained, but organisms, when diluted to 1 x 10(3) cells/ml, were susceptible. Drug-containing medium recovered from high-cell-density tests inhibited low-cell-density organisms. A fluconazole-resistant strain showed greater resistance at high planktonic cell density, in biofilm, and in resuspended biofilm than did low-density planktonic or biofilm organisms. A strain lacking drug efflux pumps CDR1, CDR2, and MDR1, while susceptible at a low azole concentration, was resistant at high cell density and in biofilm. A strain lacking CHK1 that fails to respond to the quorum-sensing molecule farnesol had the same response as did the wild type. FK506, reported to abrogate tolerance to azole drugs at low cell density, had no effect on tolerance at high cell density and in biofilm. These observations suggested that cell density has a role in the phenotypic resistance of biofilm, that neither the drug efflux pumps tested nor quorum sensing through Chk1p contributes to resistance, and that azole drug tolerance at high cell density differs mechanistically from tolerance at low cell density.     

Suture fixation of dislocated endothelial grafts

PURPOSE: To share the experience of suturing the displaced endothelial grafts in three patients who developed this complication following a posterior endothelial keratoplasty. METHODS: Prospective evaluation of three patients who underwent surgical revision by suture fixation for dislocated endothelial graft. The surgeries were performed immediately after noting the complication during the post-op visits and were followed up for 6 months. Assessments at follow-up visits include visual acuity, pachymetry, endothelial cell count, topography, and corneal slit-lamp digital photography. RESULTS: No significant postoperative complications were encountered in any of the three eyes after graft suturing. The vision was worse than hand movements in all, following the graft dislocation and this improved to an average of 20/50 at 6-month post-op. In two of the three eyes the endothelial cell count reduced from 2600 cells preoperatively to 1251 and 988 cells, respectively. Mean topographic astigmatism after the suture removal was 2.4 D. CONCLUSION: Suture fixation of early endothelial graft dislocation seems to be a good alternative in dislocated endothelial discs as it provides a good refractive and visual outcome, instead of converting it to a standard full-thickness penetrating keratoplasty.     

Application of polymerase chain reaction-based restriction fragment length polymorphism in typing ocular rapid-growing nontuberculous mycobacterial isolates from three patients with postoperative endophthalmitis

PURPOSE: We describe postoperative endophthalmitis caused by rapid-growing nontuberculous mycobacteria (RGNTM) in 3 patients after small-incision cataract surgery with intraocular lens (IOL) implantation performed elsewhere and referred to us for management. Subsequent identification and confirmation was carried out with biochemical tests and polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). MATERIALS AND METHODS: The corneal scraping and eviscerated material of the first patient, the corneal button and the IOL of the second patient, and the corneal scraping of the third patient were processed for routine bacteriologic studies including acid-fast bacilli (AFB) by smear (excepting the IOL) and culture. Subsequent identification of the RGNTM was carried out by using biochemical tests and PCR-RFLP by using primers targeting the heat shock protein 65 region of mycobacteria. RESULTS: AFB smear was positive in all 3 patients. The corneal scraping of the first patient, the corneal button and IOL of the second patient, and the corneal scraping of the third patient were culture positive for RGNTM and were identified as Mycobacterium abscessus in the first and second patients and M. fortuitum sorbitol-positive third biovariant in the third patient. CONCLUSIONS: A clinical suspicion of infection by RGNTM in delayed-onset postoperative endophthalmitis should be considered when resistance to standard therapy is encountered.     

Therapy after cyclin-dependent kinase inhibition in metastatic hormone receptor-positive breast cancer: Resistance mechanisms and novel treatment strategies

Endocrine therapy has been the standard of care for patients with metastatic hormone receptor (HR)-positive, HER2-negative breast cancer since the 1970s, improving survival while avoiding the toxicities associated with cytotoxic chemotherapy. However, all HR-positive tumors ultimately develop resistance to endocrine therapy. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have more recently become an important component of the management of this breast cancer subtype, significantly delaying time to the disease progression and improving survival when combined with endocrine therapy. However, as with endocrine therapy alone, treatment resistance remains a universal phenomenon. As more women receive CDK4/6 inhibitors as part of their treatment, the management of de novo and acquired resistance to combined CDK4/CDK6 inhibitor plus endocrine therapy regimens has emerged as an important clinical challenge. Several resistance mechanisms have been described, including alterations in the CDK4/6/cyclin D complex or its major effector retinoblastoma protein (pRb), bypass signaling through other cyclin/CDK complexes and activation of upstream signaling pathways, in particular the PI3K/mTOR pathway, but robust biomarkers to predict resistance remain elusive, and the role for continuing CDK4/6 inhibitors after progression remains under investigation. Novel strategies being evaluated in clinical trials include the continuation of CDK4/6 inhibitors through progression, as well as triplet therapy combinations with PI3K inhibitors or immune checkpoint inhibitors.