Mycophenolate mofetil treatment for primary glomerular diseases

BACKGROUND: Treatment of primary glomerular diseases may be unsuccessful or have potential toxicities. Therefore, we evaluated the use of mycophenolate mofetil (MMF) for empirical treatment of primary glomerulopathies. METHODS: Forty-six patients with biopsy-proven primary glomerulopathies received MMF for > or =3 months as adjunctive or primary treatment. Median (range) 24-hour urine protein to creatinine ratio (Up/c) and serum creatinine at the start and end of MMF therapy were compared using the Wilcoxon signed-ranks test. RESULTS: Overall, the median Up/c decreased from 4.7 (range <0.1, 20.3) to 1.1 (<0.1, 14.3; P < 0.001) at the end of MMF treatment with no significant change in median serum creatinine 1.3 (0.6 to 6.1) to 1.2 (0.5 to 6.5) mg/dL. Median serum albumin increased from 3.4 (1.4, 4.6) to 4.1 (1.7, 48) g/dL (P < 0.001) and the median serum cholesterol decreased from 270 (148, 795) to 220 (140, 309) mg/dL (P < 0.001) post-treatment. For those with minimal change disease, a complete steroid withdrawal was accomplished in 5/6 steroid dependent patients. Focal segmental glomerulosclerosis (FSGS) patients had a median Up/c that decreased from 2.7 (0.1, 20.3) to 0.8 (<0.1, 8.2; P = 0.001) in 18 patients. In membranous nephropathy (MN) patients, the median Up/c decreased from 7.3 (0.1, 18.5) to 1.5 (<0.1, 14.3) (P = 0.001) in 17 patients. No significant change in median serum creatinine was detected in FSGS or MN patient groups during treatment. CONCLUSIONS: Empirical MMF therapy in the majority of patients with primary glomerulopathies was well tolerated and achieved the goals of steroid withdrawal, improvement of nephrotic syndrome, and stabilization of renal function.     

Crisis management during anaesthesia: laryngospasm

Background: Laryngospasm is usually easily detected and managed, but may present atypically and/or be precipitated by factors which are not immediately recognised. If poorly managed, it has the potential to cause morbidity and mortality such as severe hypoxaemia, pulmonary aspiration, and post-obstructive pulmonary oedema.

Objectives: To examine the role of a previously described core algorithm "COVER ABCD–A SWIFT CHECK", supplemented by a specific sub-algorithm for laryngospasm, in the management of laryngospasm occurring in association with anaesthesia.

Methods: The potential performance of this structured approach for the relevant incidents amongst the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved.

Results: There were 189 reports of laryngospasm among the first 4000 incidents reported to AIMS. These were extracted and analysed. In 77% of cases laryngospasm was clinically obvious, but 14% presented as airway obstruction, 5% as regurgitation or vomiting, and 4% as desaturation. Most were precipitated by direct airway stimulation (airway manipulation, regurgitation, vomiting, or blood or secretions in the pharynx), but patient movement, surgical stimulus, irritant volatile agents, and failure to deliver the anaesthetic were also precipitating factors. Desaturation occurred in over 60% of cases, bradycardia in 6% (23% in patients aged <1 year), pulmonary oedema in 4%, and pulmonary aspiration in 3%. It was considered that, correctly applied, the combined core algorithm and sub-algorithm recommended for the diagnosis and management of laryngospasm would have led to earlier recognition of the problem and/or better management in 16% of cases.

Conclusion: Laryngospasm may present atypically and, if not promptly managed effectively, may lead to morbidity and mortality. Although usually promptly recognised and appropriately managed, the use of a structured approach is recommended. If such an approach had been used in the 189 reported incidents, earlier recognition and/or better management may have occurred in 16% of cases.

     

Crisis management during anaesthesia: regurgitation, vomiting, and aspiration

Background: Regurgitation, vomiting and aspiration may occur unexpectedly in association with anaesthesia. "Aspiration/regurgitation" was ranked fifth in a large collection of previously reported incidents that arose during general anaesthesia. These problems are encountered by all practising anaesthetists and require instant recognition and a rapid, appropriate response. However, the diagnosis may not be immediately apparent as the initial presentation may vary from laryngospasm, desaturation, bronchospasm or hypoventilation to cardiac arrest.     

Mixed incontinence: The misclassification of patients and limitations of clinical trials

Mixed urinary incontinence (MUI) has become a diagnosis of increased interest in the fields of urology and urogynecology, as drugs and treatments targeting urgency-related and stress-related symptoms are being developed and evaluated. We think the concept of “mixed incontinence” warrants revisiting because confounding clinical conditions exist, which result in a heterogeneous population of patients receiving the same diagnosis. The classification system for patients with signs and symptoms of MUI should undergo refinement. In addition, clinical trials for MUI should clearly delineate the lower urinary tract signs and symptoms found in the study population. Current study outcomes do not apply to the entire mix of patients included under the diagnosis of MUI, thus limiting their value. Investigation into the pathophysiologic basis of MUI and refinement of the definition of MUI are necessary if we are to evaluate the effect of future treatments on stress and urge components.     

Epidemiology of sepsis in Victoria, Australia

OBJECTIVE: To determine the clinical and epidemiologic characteristics of patients with sepsis admitted to hospitals in Victoria, Australia, including the incidence of sepsis and severe sepsis, utilization of intensive care unit (ICU) resources, and hospital mortality. DESIGN: A population-based hospital morbidity database generated from hospital discharge coding. SETTING: State of Victoria, Australia (population, 4.5 million), the 4-yr period from July 1, 1999, to June 30, 2003. PATIENTS: A total of 3,122,515 overnight hospitalizations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall hospital incidence of sepsis was 1.1%, with a mortality of 18.4%. Of septic patients, 23.8% received some care in an ICU. For these patients, hospital mortality was 28.9%. Severe sepsis, defined by sepsis and at least one organ dysfunction, occurred in 39% of sepsis patients and was accompanied by a hospital mortality of 31.1%. Fifty percent of patients with severe sepsis received at least some care in an ICU. CONCLUSIONS: Australian state hospital administrative data reveal epidemiologic features of sepsis and severe sepsis that are strikingly similar to those recently reported from comparable populations in North American and Europe. This suggests that lessons learned in this area may be directly applicable internationally.     

Knowledge of general public and health professionals about tetanus immunization

Objective : To study the awareness among general public and health care providers about tetanus immunization in relation to injuries, and their knowledge about tetanus immunization schedules in children, pregnant females and adults.Methods : It was a cross-sectional study done at a perfect health mela and all the government allopathic health agencies in Delhi.Results : The knowledge of tetanus immunization was poor among general public as well as health care providers. A substantial proportion of them indicated tetanus injection after every injury, which was unwarranted. The knowledge of tetanus immunization schedule for adults was poor among all categories of respondents, though it was comparatively better for pregnant females, but only 75% of doctors and 51.1 % of nursing personnel correctly knew the immunization schedule against tetanus in children.Conclusion : There is a need to upgrade the level of knowledge among health care providers so as to ensure that schedules of tetanus are followed properly and unnecessary repeated immunizations are avoided and the same knowledge is passed on to the general public also.     

Risk factors of substance use among street children from Delhi

OBJECTIVE: To estimate the magnitude of and socio-demographic factors related to substance use among street children in Delhi. DESIGN: Observational study. METHODS: 115 male street children aged 6 to 16 years were interviewed at the time of their admission to an observation home. RESULTS: More than half of the subjects had indulged in substance use before coming to the observation home. The agents consumed were nicotine,inhalants, alcohol and cannabis. On application of multiple logistic regression, maltreatment of the child by family members was found significant predictor of substance use in the study group. CONCLUSION: Substance use in street children is associated with unstable homes and maltreatment.     

Lacrimal sac rhinosporidiosis: a case report

Rhinosporidiosis is a disease caused by Rhinosporidium seeberi. It usually affects the nasal mucosa and rarely the conjunctiva, lacrimal sac, tonsils, and skin. We present a case study of an isolated lacrimal sac rhinosporidiosis in an 8-year-old girl who was a migrant from Orissa, an Eastern coastal state of India. The mode of presentation and management of this case with a review of literature is discussed in brief.     

A comparison of the tolerability of two dilution volumes (0.5 mL and 1.0 mL) of a purified chick embryo cell rabies vaccine administered intramuscularly to healthy adult volunteers: A randomized, intraindividual, assessor-blind study

Background: The current recommendation of the manufacturer for administering purified chick embryo cell rabies vaccine (PCECV) is to reconstitute the contents with 1.0 mL of water for injection (WFI). However, it has been debated whether a lower volume of WFI (0.5 mL) is likely to cause less pain.Objectives: The aims of this study were to compare the tolerability of PCECV administered IM at a volume of 0.5 mL versus 1.0 mL of diluent and to determine the immunogenicity of the vaccine when administered according to the World Health Organization-recommended preexposure prophylaxis regimen for rabies immunization.Methods: This comparative, intraindividual, assessor-blind study was conducted at the Department of Clinical Pharmacology, Topiwala National Medical College and Bai Yamunabai Laxman Nair Charitable Hospital Mumbai, India). Healthy volunteers aged 18 to 50 years received, by randomized sequence, 3 IM injections of PCECV, diluted in 0.5 mL or 1.0 mL of WFI, on study days 0, 7, and 28. Tolerability was assessed at 30 minutes and 24 hours after injection and included assessments for local and systemic reactions. For immunogenicity assessment, rabies virus-neutralizing antibody 0RVNA) titers were assayed at baseline and on day 49 (ie, 3 weeks after the third injection).Results: Twenty-six subjects (24 men, 2 women; mean [SD] age, 22.4 [2.4] years; mean [SD] body weight, 59.0 [11.3] kg) entered the study. Twenty-five subjects were included in the tolerability assessment; 24 in the immunogenicity assessment. No statistically significant differences were found between dilutions in the frequency of local and systemic reactions. Most reactions were mild. All subjects developed RVNA titers >0.5 IU/mL (indicative of protection) by day 49.Conclusions: In this population of healthy volunteers, a full antigenic dose of PCECV in a dilution of 0.5 mL WFI is as well tolerated locally and systemically as in a dilution of 1.0 mL. All subjects developed levels of RVNA far exceeding 0.5 IU/mL, which is indicative of protection against rabies.     

Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer

OBJECTIVE: Matrix metalloproteinases (MMPs) and their physiological inhibitors, the tissue inhibitors of MMPs (TIMPs), play a key role in tumor cell invasion, angiogenesis, and growth. The aim of this study was to determine the expression and cellular distribution of MMP-26, TIMP-3, and TIMP-4 in endometrial cancers and benign endometrium throughout the menstrual cycle and the correlation with tumor histological subtype, stage, and grade. METHODS: Immunohistochemical analysis using polyclonal antibodies generated against pro- and active MMP-26, and mono- and polyclonal antibodies specific to TIMP-3 and TIMP-4, respectively, was performed. RESULTS: MMP-26, TIMP-3, and TIMP-4 are expressed in endometrial carcinomas (N = 86) and benign endometrium (N = 50) from various stages of the menstrual cycle. Semi-quantitative analysis of staining intensity indicated that endometrial carcinomas expressed more MMP-26, TIMP-3, and TIMP-4 compared to benign endometrium from the postmenopausal period, but not from the secretory phase of the menstrual cycle. The highest staining intensity was associated with endometrial epithelial cells, followed by vascular endothelial cells, myometrial smooth muscle cells, and endometrial stromal cells. Increased staining intensity of MMP-26 and TIMP-3 correlated with grade III tumors and MMP-26 and TIMP-4 with the depth of myometrial invasion in tumors histologically characterized as endometrioid adenocarcinoma, clear-cell, and papillary serous carcinoma staged/graded based on FIGO criteria. CONCLUSION: MMP-26 and TIMP-4 are expressed in endometrium and endometrial carcinoma and their elevated expression and correlation with myometrial invasion suggests that MMP-26 and TIMP-4 may play a key role in endometrial tumor progression.