Biomedical subjects

A Thakur

Publications and source records attributed to A Thakur.

At least 19 recordsLinked to original sources

PubMed2003

Role and regulation of CXC-chemokines in acute experimental keratitis.

The aim of this study was to elucidate the expression of chemokines, their role and regulation in bacterial corneal infection using three bacterial strains (Pseudomonas. aeruginosa- invasive, cytotoxic and contact lens induced acute red eye strains) which have been shown to produce three distinct patterns of corneal disease in the mouse. The predominant chemokine expressed in response to all three strains was MIP-2. Prolonged expression of high levels of MIP-2 was associated with increased severity of corneal inflammation. Significantly reduced disease severity upon administration of anti-MIP-2 antibodies suggested that MIP-2 may play an important role in the pathogenesis of Pseudomonas keratitis at least in part by being a major chemoattractant for polymorphonuclear leukocytes (PMN) recruitment. Interestingly, the numbers of bacteria in eyes with neutralized MIP-2 activity did not decrease even though the severity of the disease was decreased. This implies PMNs as the major destructive factor in microbial keratitis. Further, neutralization of IL-1beta activity alone using monoclonal antibodies resulted in significant reduction of both MIP-2 and KC activity indicating that chemokine levels were regulated by IL-1beta. These studies demonstrate that the regulation of MIP-2 activity may be beneficial in reducing corneal damage during microbial keratitis in rodents and perhaps that regulation of the human homologue of MIP-2, IL-8, may be useful for controlling keratitis in humans.

Acute Disease↗

PubMed2003

Efficacy of GM-CSF as an adjuvant to hepatitis B vaccination in patients with chronic renal failure--results of a prospective, randomized trial.

BACKGROUND: Chronic renal failure patients on hemodialysis are at an increased risk of acquiring hepatitis B infection. Hence vaccination against hepatitis B assumes great importance in these patients. However, the response to hepatitis B vaccination is poor, even when 4 double doses (40 microg) of the vaccine are given. This study was conducted to determine the efficacy of GM-CSF as an adjuvant to hepatitis B vaccine in CRF patients. METHODS: CRF patients including both hemodialysis (HD) and non-dialysis (ND) patients were randomized to receive either placebo or a single injection of GM-CSF (in varying doses of 50 microg, 100 microg, 150 microg) a day prior to the 1st dose of recombinant hepatitis B vaccine (40 microg). Three more doses of the vaccine were given at 1, 2, and 6 months. The anti-HBs antibody titres were measured by ELISA at 3 and 7 months. Patients having antibody titres less than 10 IU/L were considered non-responders. The response rate and mean antibody titers were compared between the control (I) and GM-CSF (II) groups. RESULTS: In group I, 31 and 27 patients were available for evaluation at 3 and 7 months respectively. In group II, 33 and 28 patients could be evaluated at the same time points. Within the control group (group I), the response rate in hemodialysis patients (63.6%) was lower as compared to non-dialysis patients (81.2%). The response rate in group II was higher than that in group I at both 3 months as well as 7 months (78.1% vs. 62.3% and 89.3% vs. 74.1%, p = ns). The best response rates in group II were observed when GM-CSF was used in a dose of 150 microg (90.9% at 3 months and 100% at 7 months). The mean antibody titers were also found to be higher in the group II as compared to group I (409.6 vs. 243.9 IU/L, p = 0.01). CONCLUSION: The results of this randomized, prospective study suggest that: 1. Patients with chronic renal failure should be vaccinated for hepatitis B as chronic renal insufficiency is established. 2. GM-CSF is an effective adjuvant to hepatitis B vaccine in these patients especially when a priming dose of 150 microg is used prior to 1st dose of hepatitis B vaccination.

Adult↗

PubMed2003

Effect of membrane composition on cytokine production and clinical symptoms during hemodialysis: a crossover study.

BACKGROUND: Intradialytic symptoms including hypotension have been reported during dialysis and it has been suggested that these are related to the release of cytokines like IL-1beta and TNFalpha by blood mononuclear cells when they get activated either due to contact with the dialyzer membrane or by compliment activation. OBJECTIVE: To study the relationship between hemodialysis symptoms, cytokine production, and dialyzer membrane composition. METHOD: In a randomized prospective crossover study, 20 ESRD patients on maintenance hemodialysis were studied over cuprophan (CU) and polysulfone (PS) low flux dialyzer membranes for three weeks each undergoing a biweekly dialysis schedule of 4 h sessions. Serial IL-1beta and TNFalpha levels were measured over 0, 15, 240 min during the first use of the dialyzer for all patients on both membranes. Intradialytic symptoms were monitored in a total of 240 dialysis sessions. RESULTS: IL-1beta levels increased from 16.6 +/- 2.2 to 64.8 +/- 25.1 pg/mL on CU and 21.5 +/- 3.7 to 103.5 +/- 30.7 pg/mL on PS membrane over the 4-h dialysis session. Similarly TNFalpha increased from 42.8 +/- 4.5 to 354.9 +/- 80.4 pg/mL on CU and 117.1+/- 53.7 to 387.0 +/- 78.0 pg/mL on PS membrane. IL-1beta levels increased significantly with PS membrane while TNFalpha rise was significant with both the membranes. Nausea was the most common symptom occurring in 138 dialysis sessions (57.5%). Vomiting, chest pain, fever, chills, and breathlessness occurred significantly more during dialysis with CU membrane as compared with PS membrane (P < 0.01). Nausea, cramps, back pain, itching, restlessness, post dialysis fatigue, and hypotension did not differ between the two membranes. The mean rise in the cytokine levels during the first 15 min of sessions where the symptoms occurred, when compared with the mean rise in sessions where the symptoms did not occur, did not reveal any significant difference. Cytokine release did not correlate with the occurrence of intradialytic symptoms. CONCLUSION: Both CU and PS membranes increase circulating cytokine levels. More intradialytic clinical symptoms are seen in dialysis with CU as compared with PS membrane but the rise in cytokines IL-1beta and TNFalpha does not appear to be responsible for them.

Adolescent↗

PubMed2002

Catheter associated urinary tract infections in neurology and neurosurgical units.

OBJECTIVE: Catheter associated bacteriuria is the most common infection acquired in hospitals. The objective of the study was (1) to study the incidence of bacteriuria following indwelling urethral catheterization in patients with short-term vs long-term catheterization (2) to define the antibiotic resistance pattern among these isolates so that the study can provide guidelines for choosing an effective antibiotic against infections in catheterized patients. METHODS: This is a prospective study carried out over a period of 18 months in Neurology/Neurosurgical patients who had indwelling catheters for > or =48 h. RESULTS: In this study, 68 out of 800 (8.5%) adult inpatients acquired urinary tract infection following indwelling bladder catheterizations. The risk was significantly higher for female, elderly patients, critically ill and patients on prolonged catheterization. Among the bacterial pathogens, Escherichia coli was the commonest organism isolated (32.9%) followed by Pseudomonas sp. (15.1%) and Staphylococcus aureus (12.3%). Candida sp. comprised 13.7% of all isolates. Among Gram negative bacterial pathogens maximum number of isolates were sensitive to Amikacin (sensitivity of 42%). All Gram positive organisms were however sensitive to Vancomycin. CONCLUSIONS: Our results provide guidelines for choosing salvage therapy against hospital resistant strains causing infection in catheterized patients. However, antibiotics seem to prevent urinary tract infections but primarily in patients catherized for short duration, i.e. 3-14 days and not in patients with long-term catheterization.

Aged↗

PubMed2002

Balance of pro- and anti-inflammatory cytokines correlates with outcome of acute experimental Pseudomonas aeruginosa keratitis.

The purpose of this study was to elucidate the expression of pro- and anti-inflammatory cytokines in mouse corneas infected with Pseudomonas aeruginosa. Three bacterial strains (invasive, cytotoxic, or CLARE [contact lens-induced acute red eye]) which have recently been shown to produce distinct patterns of corneal disease in the mouse were used. The left mouse (BALB/c) corneas were scarified and infected with 2 x 10(6) CFU of one of the three P. aeruginosa strains, while right eyes served as controls. Animals were examined at 1, 4, 8, 16, and 24 h with a slit lamp biomicroscope to grade the severity of infection. Following examination, eyes were collected and processed for histopathology, multiprobe RNase protection assay for cytokine mRNA, enzyme-linked immunosorbent assay to quantitate cytokine proteins, and myeloperoxidase activity to quantitate polymorphonuclear leukocytes. The kinetics of appearance and magnitude of expression of key cytokines varied significantly in the three different phenotypes of P. aeruginosa infection. The predominant cytokines expressed in response to all three phenotypes were interleukin-1 beta (IL-1 beta), IL-1Ra, and IL-6. In response to the invasive strain, which induced severe corneal inflammation, significantly lower ratios of IL-1Ra to IL-1 beta were present at all time points, whereas corneas challenged with the CLARE strain, which induced very mild inflammation, showed a high ratio of IL-1Ra to IL-1 beta. The outcome of infection in bacterial keratitis correlated with the relative induction of these pro- and anti-inflammatory cytokines, and exogenous administration of recombinant rIL-1Ra (rIL-1Ra) was able to reduce the disease severity significantly. These findings point to the therapeutic potential of rIL-1Ra protein in possible treatment strategies for bacterial keratitis.

Acute Disease↗

PubMed2001

Ontogeny of fetal rabbit upper gastrointestinal motility.

BACKGROUND: The gastrointestinal (GI) tract performs the digestion, propulsion, and absorption of nutrients both pre- and postnatally, although little is known about the development of fetal motility. We evaluated the development of GI motility using a novel fetal rabbit model. METHODS: Nine pregnant rabbits were obtained and three litters were studied at day 24 (n = 24), 27 (n = 29), and 30 (n = 24) of their 31-day gestation. Under ultrasound guidance fetal position was identified, a spinal needle was percutaneously inserted into each fetal stomach, and fluorescein, labeled with color-coded microspheres, was injected. Two hours later, fetuses were delivered and weighed, and the small intestine was harvested. The absolute length of fluorescein traveled was measured by ultraviolet light optical density and the percentage motility was calculated by dividing the absolute length of fluorescein traveled by the total small intestinal length. RESULTS: All injected fetuses survived. The length of fluorescein traveled significantly increased from day 24 (8.1 +/- 2.1 cm) to day 27 (18.8 +/- 4.6 cm) and 30 (22.6 +/- 5.2 cm). The length of fluorescein traveled significantly correlated with body weight on day 27 and 30. Calculated percentage motility significantly increased from day 24 to 30. However, percentage motility showed no correlation with fetal weight. CONCLUSIONS: This study describes a novel rabbit model for the assessment of in vivo fetal GI motility. Motility matured during the last third of gestation when assessed by the absolute length of fluorescein travel and the percentage motility. These results confirm that late-gestation fetuses have developed sufficient motility to propel potential nutrients, drugs, or gene therapy vectors to the small intestinal absorptive surface area.

Animals↗

PubMed2001

Scrotal abscess following appendectomy.

Postoperative infectious complications in children following perforated appendicitis present in diverse ways. We present two unusual complications of appendectomy for perforated appendicitis: an acute scrotum after open and laparoscopic appendectomy. A retrospective review of two cases of scrotal abscess following appendectomy at our hospital as well as a MEDLINE search was performed to review the clinical presentation, etiology, type of treatment, and outcome of these patients. Although scrotal inflammation occurring postoperatively in a patient with perforated appendicitis may be due to an incarcerated hernia, it is much more likely to be due to a scrotal abscess. Patients without a patent processus vaginalis or inguinal hernia at initial presentation of peritonitis must be carefully followed in the postoperative period and explored early if testicular or scrotal pain becomes manifest.

Abscess↗

PubMed2001

Subtotal hysterectomy for uterine rupture.

OBJECTIVE: The aim of this paper was to stratify patients with uterine rupture in extremis (with hypotension, change in vital organ function, and altered mental status) and evaluate outcome for patients undergoing subtotal hysterectomy (STH) vs. uterine repair (UR). METHODS: Of 39667 hospital deliveries between 1993 and 1998 at a university hospital, 367 presented with uterine rupture. Of these, 96 presented in extremis and had an irregularly torn uterus found at operation. Charts were retrospectively reviewed to stratify patient population with uterine rupture and their outcome. Results were analyzed using Fisher's exact test. RESULTS: Patients with uterine rupture were 31-35 years old, para> or =3, had received no antenatal care, and presented with rupture in the lower uterine segment. Sixty-one patients underwent STH while 35 underwent UR. The groups were similar with respect to patient age, parity, cause of rupture, and clinical condition at the time of evaluation (P=0.2). The operative time for STH was significantly less than UR, 35 min vs. 75 min (P<0.01). Maternal mortality was significantly higher in patients undergoing UR vs. STH, 46% vs. 20% (P=0.01). Maternal morbidity occurred in 30% of patients undergoing STH vs. 50% in patients undergoing UR (P=0.01). The time to discharge was significantly less in patients undergoing STH compared to UR, 14.5 days vs. 27 days (P<0.01). CONCLUSIONS: Patients with uterine rupture in extremis tend to be young, multiparous, receive no antenatal care, and have uterine rupture of the lower segment. STH significantly lowered operative time, morbidity, time to discharge, and mortality than UR in patients in extremis with uterine rupture.

Adult↗

PubMed2001

Expression of macrophage migration inhibitory factor during Pseudomonas keratitis.

Macrophage migration Inhibitory factor (MIF) is a recently rediscovered pro-inflammatory cytokine, and has been shown to play a role in the regulation of neutrophil chemokines and angiogenesis. Corneal epithelial and endothelial cells have been shown to express MIF. This study evaluated the expression of MIF during Pseudomonas keratitis in mice and in vitro using a corneal epithelial cell line. Three strains of P. aeruginosa, 6294 (invasive strain), 6206 (cytotoxic strain) and Paer1 (non-infectious strain) were used. Both cytotoxic and invasive strains were isolated from human corneal ulcers and the Paer1 strain was isolated from a non-infectious condition. Following challenge in mouse corneas or a corneal epithelial cell line, corneal homogenates or lysed corneal epithelial cells were used to isolate RNA. Migration inhibitory factor mRNA expression in the mouse cornea or human corneal epithelial cells was examined by reverse transcription-polymerase chain reaction analysis, and was found to be expressed as early as 4 h after the injury (scratch controls) or infection in the mouse corneas. Migration inhibitory factor mRNA in scratch controls and Paer1-inoculated corneas showed peak levels at 4 h post-challenge and this dropped by 24 h post-challenge. Corneas challenged with invasive and cytotoxic strains showed peak expression 24 h post-challenge. Migration inhibitory factor mRNA levels were significantly higher in invasive and cytotoxic strain inoculated corneas compared to Paer1 inoculated corneas. Challenging the corneal epithelial cell line with Pseudomonas 6294 and 6206 strains induced peak expression at 8 h and levels were decreased by 12 h. Epithelial cells inoculated with recombinant human interleukin-1beta protein induced very high levels of MIF mRNA at all time points compared to infected and control corneal epithelial cells. High expression of MIF in the infected corneas suggests that it may have a role in the pathogenesis of corneal disease induced by invasive and cytotoxic strains of P. aeruginosa.

Animals↗

PubMed2001

Regulatory role of IL-1beta in the expression of IL-6 and IL-8 in human corneal epithelial cells during Pseudomonas aeruginosa colonization.

Pseudomonas aeruginosa is a virulent pathogen and is frequently associated with bacterial keratitis. Recent studies have shown that high levels of interleukin (IL)-1beta and macrophage inflammatory protein-2 are associated with the severity of corneal infection. Interleukin-1beta is a principal inflammatory mediator. Understanding the regulatory role of IL-1beta would provide better understanding of host responses during P. aeruginosa corneal infection. A human corneal epithelial (HCE) cell line and three P. aeruginosa strains were used in this experiment. Confluent HCE cells were challenged with P. aeruginosa and monoclonal antihuman IL-1beta antibody (IL-1beta mAb). The culture supernatants were collected for measuring cytotoxicity and protein levels of IL-1beta, IL-8 and IL-6 by enzyme-linked immunosorbent assay. Results showed that HCE cells expressed low levels of IL-1beta and high levels of IL-6 and IL-8 during P. aeruginosa colonization. Paer1-colonized HCE cells produced higher levels of IL-1beta, IL-6 and IL-8 protein compared to those produced by 6206- and 6294-colonized HCE cells. Administration of IL-1beta mAb decreased the production of IL-8 and IL-6. In conclusion, P. aeruginosa-colonized HCE cells produced low levels of IL-1beta and high levels of IL-6 and IL-8. Neutralizing IL-1beta protein significantly downregulated the production of IL-8 and IL-6.

Cell Line↗

PubMed2001

Methodology standards associated with quality reporting in clinical studies in pediatric surgery journals.

BACKGROUND/PURPOSE: Reports of clinical trials often lack adequate descriptions of design and analysis; recent attention has focused on improving this omission so readers can properly assess the strength of the findings and draw their own conclusions. Similar analysis of study design and methodologic standards associated with quality reporting has not been carried out for pediatric surgery journals. METHODS: All studies (n = 642) published in 1998 in Journal of Pediatric Surgery (JPS) and Pediatric Surgery International (PSI), were reviewed for demographic data and study design. The frequency of reporting of 11 basic elements of design and analysis was evaluated in randomized clinical trials (RCT), nonrandomized clinical trials (NRCT), and retrospective cohorts (RC) from JPS by consensus of 2 assessors. RESULTS: Of the 642 studies, 17% of articles (111 of 642) were classified as clinical studies. Sixty-three were comparative studies and consisted of RC (n = 48), NRCT (n = 12), and RCT (n = 3). Two-thirds of articles published were either case reports or case series (431 of 642), and 16% were basic science articles. Demographic analysis showed a wide range of topics addressed, 4 authors per article, and multiple country of origin of authors. More than 66% of all RCT in JPS reported on eligibility criteria, admission before allocation, random allocation, method of randomization, patients' blindness to treatment, treatment complications, statistical analyses, statistical methods, loss to follow-up, and statistical methods; 2 elements of design and analysis, however, were poorly reported: blind assessment of outcome (33%) and power (17%). CONCLUSIONS: There were few randomized, controlled trials in pediatric surgery journals, and further attention should be given to evaluate the causal factors. Nine elements of quality reporting were well reported; however, 2 others were poorly reported; this may improve if editors of pediatric surgical journals provide authors with guidelines on how to report clinical trial design and analysis.

Authorship↗

PubMed2001

Gene transfer to the embryo: strategies for the delivery and expression of proteins at 48 to 56 hours postfertilization.

BACKGROUND/PURPOSE: Although gene and protein transfer may potentiate the cure of genetic disease, current strategies involving fetal gene therapy remain nonfocal and confounded by the lack of imaging techniques and in vivo markers for precise gene transfer. METHODS: Fourteen white Leghorn chick eggs were incubated for 48 to 56 hours postfertilization until they reached stages 11 to 16, about 3 mm in size. In 7 chick embryos, a glass needle was placed at the midbrain/hindbrain level and 1 x 10(7) pfu of an adenovirus containing the green fluorescent protein (GFP) reporter gene was injected into the lateral head. In another 7 chicken embryos, colored agarose beads coated with Sonic hedgehog (Shh) protein were implanted at the level of the hindbrain under direct microscopy. The eggs were then sealed, incubated at 37 degrees C for 24 hours, and reimaged using fluorescent microscopy and confocal laser microscopy. RESULTS: At 24 hours postinjection, all embryos were alive and were imaged in vivo. Fluorescent microscopic imaging showed green fluorescence in the region of the injection site in all the embryos. In embryos that underwent bead placement, the beads were visualized under microscopy in the lateral hindbrain of all embryos, and the presence of the Shh protein was confirmed using fluorescein isothiocyanate (FITC)-conjugated secondary antibody. CONCLUSIONS: This study shows that embryonic 3-mm chick embryos survive adenoviral transduction or agarose bead implantation in a focal manner in vivo and that this delivery results in production of imageable levels of protein. This may be used in mammalian systems, including humans, to introduce genes and proteins.

Animals↗

PubMed2001

Ileoanal pouch procedures in children.

PURPOSE: The aim of this study was to review the long-term experience with colectomy and the ileoanal pouch procedure (IAPP) in children from one hospital. METHODS: Between 1977 and 2001, 168 children under 18 years of age underwent colectomy and IAPP. One hundred thirty-one had ulcerative colitis (UC). Twenty-six had familial colonic polyposis (FP), 9 had Hirschsprung's disease (HD), and 2 had colonic inertia. Ninety-seven had a J-pouch, 62 had a lateral pouch, and 9 had a straight pull-through (SP). The mean age was 13.9 years. RESULTS: Complications within 2 years included pouchitis (16%), ileoanal strictures (14%), and adhesions (7%). There were no deaths. Fifty-six patients (33%) required reoperation, including 20 revisions of large pouches and 8 conversions of SP to pouches because of stool frequency. Six children (3.6%) had later pouch removal (3 had Crohn's disease). Stool frequency at 6 months was 3.8 (mean). At 6 months 5% had occasional soiling. Eighty-four percent can delay defecation over 1(1/2) hours; 82% can urinate without a bowel movement. With a mean follow-up of 11.2 years, 94.6% are functioning well. CONCLUSIONS: Colectomy with IAPP is the preferred operation for children with UC, FP, and selected HD. The J-pouch is the preferred technique because of simplicity of construction and sparsity of complications.

Adenomatous Polyposis Coli↗

PubMed2001

Impact of mentor guidance in surgical career selection.

PURPOSE: The aim of this study was to survey graduates of a university general surgical residency training program to determine factors that influenced their selection of a specialty field. METHODS: A 39-item questionnaire was mailed to 86 graduates of a university general surgery program who matriculated from 1975 to 1989. The impact of lifestyle, technology, clinical opportunity, and mentor guidance in the residents' selection of a specialty field and eventual clinical practice was assessed. Results were analyzed using Fisher's Exact test with significance determined at P less than.05. RESULTS: The response rate was 65% (56 of 86). Eighty percent of respondents identified the most important aspect influencing their choice of specialty was interest in that field; additional factors included perception of prestige, presence of clinical opportunity, mentor influence, and family priorities. Sixty-six percent of respondents chose the same career as their mentor, attributing this to the mentor's skill (n = 36, 68%), achievements (n = 35, 66%), and verbal recommendations about their specialty field (n = 24, 45%), p < 0.05. CONCLUSIONS: Surgical residents use many criteria in selecting a field of specialty with mentor guidance an important component. Knowledge of these influential areas should help training programs offer appropriate career guidance. J Pediatr Surg 36:1802-1804.

Adult↗

PubMed2001

The role of IL-1beta in the regulation of IL-8 and IL-6 in human corneal epithelial cells during Pseudomonas aeruginosa colonization.

PURPOSE: Recent studies have shown that the levels of interleukin (IL)-1beta, IL-6 and IL-8 are associated with the severity of infectious diseases. The purpose of this study was to investigate whether IL-1beta regulates the expression of IL-6 and IL-8 in human corneal epithelial cells during Pseudomonas aeruginosa colonization. METHODS: Confluent immortalized human corneal epithelial cells were challenged with P. aeruginosa 6294 in the presence of anti-human IL-1beta antibody or matched control antibody. The cells were also challenged with recombinant IL-1beta protein without bacterial colonization. Expression of IL-1beta, IL-6 and IL-8 mRNA and protein was detected by reverse transcription (RT)-PCR and by enzyme-linked immunosorbent assay (ELISA), respectively. IL-1beta localization was determined by immunohistochemistry. RESULTS: Human corneal epithelial cells expressed low levels of IL-1beta and high levels of IL-6 and IL-8 during P. aeruginosa colonization. Addition of IL-1beta Ab resulted in a significant decrease (P < 0.05) in IL-8 protein expression at 4 h, 8 h and 12 h. Addition of IL-1beta Ab reduced IL-6 protein expression at 8 h and increased IL-6 protein expression at 12 h. Addition of recombinant IL-1beta protein alone strongly stimulated the expression of IL-8 and IL-6. Immunohistochemical staining showed that IL-1beta protein was present both intracellularly and extracellularly in P. aeruginosa colonized cells. CONCLUSIONS: IL-1beta is able to modulate expression of both IL-6 and IL-8 at transcriptional and post-transcriptional levels in human corneal epithelial cells.

Cells, Cultured↗

PubMed2001

Effector mechanisms of protection against Pseudomonas aeruginosa keratitis in immunized rats.

Pseudomonas aeruginosa is an opportunistic pathogen which causes sight-threatening corneal infections in humans. The purpose of this study was to evaluate various immunization routes that may provide protection against Pseudomonas keratitis and to define the molecular mechanisms involved in the protection. Sprague-Dawley rats (10 to 12 weeks old) were immunized using paraformaldehyde-killed P. aeruginosa (strain 6206) via oral, nasal, and intra-Peyer's patch (IPP) routes followed by an ocular topical booster dose. Scratched corneas were challenged with an infective dose of P. aeruginosa. Following clinical examination, eyes were enucleated for histology, polymorphonuclear leukocyte (PMN) quantitation, bacterial count, enzyme-linked immunosorbent assay, and RNase protection assay. PMN infiltration was higher early (4 h) during the infection in immunized rats than in nonimmunized rats. Later during the infection, the number of PMNs diminished in immunized rats while in nonimmunized animals the number of PMNs continued to increase. Bacteria were cleared much faster from immunized groups than from the nonimmunized group, and the nasally immunized group had the most efficacious response among the immunized groups. Nasal and IPP immunization groups had increased cytokine expression of interleukin-2 (IL-2) and IL-5 and differed from each other for IL-6. All three immunized groups had significantly reduced IL-1 beta levels when compared with the nonimmunized rats and a significantly altered profile for CINC-1 expression. This study has shown that the route of immunization modulates the inflammatory response to ocular P. aeruginosa infection, thus affecting the severity of keratitis and adverse pathology, with nasal immunization being the most effective.

Administration, Intranasal↗

PubMed2001

Surgical treatment of severe colonic inertia with restorative proctocolectomy.

Patients with severe constipation due to colonic inertia who remain symptomatic after extensive medical therapy or partial colonic resection have occasionally been treated with ileostomy as a last resort. The hospital records of five patients with persistent symptomatic idiopathic colonic inertia were reviewed. Each of the patients had undergone extensive medical management, and eventually four underwent one or more colonic resections to relieve the recurrent abdominal distention and pain. Three of the patients eventually received a distal ileostomy, which functioned well. Anorectal manometric studies were within normal range for each of the five patients. Restorative proctocolectomy (J pouch) was therefore performed for each. With a mean follow-up of 42 months after restorative proctocolectomy each of the five patients was relieved of constipation and small bowel distention. The average number of bowel movements per 24 hours at 6 months was 4.8. All patients were able to discriminate flatus from stool, could hold back for up to 1.5 hours after the initial urge to defecate, and had total daytime continence. Each returned to work or school within 3 months, and each reported greater satisfaction with bowel function than with the ileostomy. Restorative proctocolectomy with a J pouch provides a satisfactory option for the management of patients with persistent abdominal distention and pain due to idiopathic colonic inertia.

Adolescent↗

PubMed2001

Rapid tranquilization with olanzapine in acute psychosis: a case series.

Acute, high-dose loading strategies (rapid neuroleptization) with the first-generation antipsychotics administered orally or parenterally, alone or combined with benzodiazepines, have been a commonly used treatment paradigm for controlling acutely agitated psychotic patients. The rationale was to achieve high plasma levels of drug within a shorter time period, resulting in rapid symptom mitigation. However, studies have shown that rapid neuroleptization with first-generation antipsychotics is associated with a greater incidence of side effects. To our knowledge, loading strategies with second-generation antipsychotics have not been investigated, primarily owing to a need for dose titration. Olanzapine, a second-generation antipsychotic, is well tolerated in doses ranging from 5 to 20 mg. The objective of this report was to determine experience with the use of up to 20 mg of an oral loading dose of olanzapine administered within 4 hours in the treatment of patients early in an acute psychotic phase of their illness. In the reported case series of 57 patients, olanzapine initiated at 15 to 20 mg/day was a safe and effective medication for rapidly calming the agitation of acutely agitated psychotic patients (rapid tranquilization). Furthermore, dose reduction over 2 to 3 weeks was achieved in a number of patients without appreciable loss of efficacy.

Acute Disease↗