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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 73 records · Page 4Linked to original sources
PubMed2004

Systematic review of bisphosphonates for hypercalcaemia of malignancy.

BACKGROUND: Bisphosphonates are the treatment of choice for hypercalcaemia of malignancy (HCM) but there is no consensus regarding which drug or dose should be given. We designed a systematic review to investigate the efficacy of bisphosphonates in the treatment of HCM. METHODS: We identified randomized controlled trials (RCTs) by searching electronic databases, scanning of reference lists, and consultation with experts and pharmaceutical companies. Foreign papers were translated. Inclusion criteria were RCTs, confirmed malignant disease and measurement of serum calcium (ionized or corrected for albumin) postrehydration. The primary outcome was number of patients achieving normocalcaemia. Secondary outcomes were time to normocalcaemia, time to relapse and toxicity. RESULTS: Twenty-seven papers and two abstracts, using intravenous bisphosphonates, fulfilled the inclusion criteria. Data from 26 studies were used in analyses. Due to the heterogeneity of studies, meta-analysis could not be performed. Pamidronate was more effective than placebo, mithramycin, etidronate (7.5 mg/kg) and low-dose clodronate (600 mg), but equal to higher dose clodronate (1500 mg). Clodronate and etidronate were superior to placebo; incadronate was superior to elcatonin; gallium nitrate was superior to etidronate. No difference was seen between alendronate and clodronate. Three dose finding studies showed no difference between 30-90 mg of pamidronate, but one well designed study showed increasing efficacy with increasing dose. Studies using increasing doses of ibandronate (0.6-4 mg), alendronate (2.5-15 mg), and incadronate (2.5-10mg), showed a dose response. Duration of administration of pamidronate did not affect efficacy (six studies). CONCLUSION: Bisphosphonates normalize calcium in >70% patients with minimal side effects. Aminobisphosphonates are most effective at maintaining normocalcaemia and should be given in high dose irrespective of baseline serum calcium.

Diphosphonates↗
PubMed2004

A systematic review of the role of bisphosphonates in metastatic disease.

OBJECTIVES: To identify evidence for the role of bisphosphonates in malignancy for the treatment of hypercalcaemia, prevention of skeletal morbidity and use in the adjuvant setting. To perform an economic review of current literature and model the cost effectiveness of bisphosphonates in the treatment of hypercalcaemia and prevention of skeletal morbidity. DATA SOURCES: Electronic databases (1966-June 2001). Cochrane register. Pharmaceutical companies. Experts in the field. Handsearching of abstracts and leading oncology journals (1999-2001). REVIEW METHODS: Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. Overall event rates were pooled in a meta-analysis, odds ratios (OR) were given with 95% confidence intervals (CI). Where data could not be combined, studies were reported individually and proportions compared using chi-squared analysis. Cost and cost-effectiveness were assessed by a decision analytic model comparing different bisphosphonate regimens for the treatment of hypercalcaemia; Markov models were employed to evaluate the use of bisphosphonates to prevent skeletal-related events (SRE) in patients with breast cancer and multiple myeloma. RESULTS: For acute hypercalcaemia of malignancy, bisphosphonates normalised serum calcium in >70% of patients within 2-6 days. Pamidronate was more effective than control, etidronate, mithramycin and low-dose clodronate, but equal to high dose clodronate, in achieving normocalcaemia. Pamidronate prolongs (doubles) the median time to relapse compared with clodronate or etidronate. For prevention of skeletal morbidity, bisphosphonates compared with placebo, significantly reduced the OR for fractures (OR [95% CI], vertebral, 0.69 [0.57-0.84], non-vertebral, 0.65 [0.54-0.79], combined, 0.65 [0.55-0.78]) radiotherapy 0.67 [0.57-0.79] and hypercalcaemia 0.54 [0.36-0.81] but not orthopaedic surgery 0.70 [0.46-1.05] or spinal cord compression 0.71 [0.47-1.08]. However, reduction in orthopaedic surgery was significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was GBP250 and GBP1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. CONCLUSIONS: High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting.

Bone Neoplasms↗
PubMed2004

Differential effects of psychomotor stimulants on attentional performance in rats: nicotine, amphetamine, caffeine and methylphenidate.

Nicotine can improve attentional performance in the rat as assessed by a modified five-choice serial reaction time task (5-CSRTT), but it is not known if the effect is shared with other psychomotor stimulants. This study compared the effects of nicotine, amphetamine, caffeine and methylphenidate on performance in the 5-CSRTT and determined whether presenting stimuli at unpredictable times by using variable inter-trial intervals (ITI) influenced the sensitivity of the task to the drugs. One group of male hooded rats was trained to obtain food reinforcers by nose-poking in response to 1 s light stimuli presented randomly in one of five apertures, with fixed ITI; for a second group of rats, ITI varied randomly (n=12 per group). As observed previously, nicotine (tested in doses of 0.05-0.2 mg/kg) produced dose-related improvements in accuracy, reduced omission errors and response latencies, but increased anticipatory responding. Amphetamine (0.1-0.8 mg/kg) and methylphenidate (2.5-10 mg/kg) increased accuracy and reduced response latency, and decreased anticipatory responding. Caffeine (2.5-20 mg/kg) did not improve performance except at a small dose that decreased omission errors only. Training at different levels of stimulus predictability influenced performance in the undrugged state but had little impact on profiles of responses to the drugs. The findings with methylphenidate support the potential value of the 5-CSRTT for testing drugs that may be useful in the treatment of attention deficit hyperactivity disorder.

Amphetamine↗
PubMed2003

Comprehensive deficits in performance of an attentional task produced by co-administering alcohol and nicotine to rats.

BACKGROUND: Nicotine can improve and alcohol can impair attentional performance in rats, but little is known about the effects of mixtures of the two drugs with respect to attention. AIMS: The aims were to investigate the effects of alcohol and nicotine alone and when co-administered on performance of a five-choice serial reaction time task, and to examine the impact of task difficulty by varying durations of the limited hold (LH) for availability of the reinforcer. METHODS: Male hooded rats were trained to respond (nose-poke) to a 0.5 s light stimulus presented randomly in one of five apertures to obtain food reinforcers. Three groups of rats trained with different LH values were used (n = 10). RESULTS: The first experiment showed that training at different LH values had little effect on performance when the LH value during testing was held constant. Experiment 2 showed that alcohol (0.4-1.6 g/kg, i.p.) had no effect on the percentage of correct responses (accuracy) but it impaired all speed-related indices. In the third experiment, the effects of nicotine (0.1 and 0.2 mg/kg, s.c.) were determined alone and on the dose-response curve for alcohol (0.4-1.2 g/kg, i.p.). Nicotine alone produced small improvements in performance whereas co-administration of nicotine and alcohol produced large decrements at doses of alcohol that themselves only slightly impaired performance. These decrements included impairments of accuracy as well as of anticipatory responding, omission errors, response latencies and reinforcers earned. There were no marked or consistent interactions of drug effects with LH values. CONCLUSIONS: Task performance was disrupted to a much greater extent by co-administration of alcohol and nicotine than by alcohol alone; therefore, it seems unlikely that an ability of nicotine to reverse the effects of alcohol can account for associations between the use of the two substances.

Animals↗
PubMed2003

Laparoscopic extraperitoneal approach to acutely incarcerated inguinal hernia.

BACKGROUND: Laparoscopic treatment of acutely incarcerated inguinal hernia is uncommon and still controversial. Those being performed almost all use the transabdominal (TAPP) approach. The authors here present their experience with totally extraperitoneal (TEP) repair of acutely incarcerated hernia. METHODS: A retrospective review was undertaken to evaluate the authors' experience with this procedure over a 4-year period. There were 16 cases, 5 of which were performed using a conventional anterior repair. These 5 cases were excluded from the review. The surgery for all of the remaining 11 acutely incarcerated hernias was started laparoscopically using the TEP approach. Eight of the cases were completed this way, whereas three were converted to the open procedure. In addition to standard TEP repair techniques, a releasing incision is required for acutely incarcerated direct, indirect, or femoral hernias. With a direct hernia, the opening of the defect is enlarged to allow safe dissection of its contents. A releasing incision is made at the anteromedial aspect of the defect to avoid injury to the epigastric or iliac vessels. With an indirect hernia, several additional steps are required. The epigastric vessels may be divided; an additional trocar may be placed laterally below the linea semicircularis to facilitate dissection of the sac and to assist with suturing of the divided sac; and the deep internal ring is divided anteriorly at the 12 o'clock position toward the external ring, facilitating dissection of the indirect sac. With a femoral hernia, a releasing incision is made by carefully incising the insertion of the iliopubic tract into Cooper's ligament at the medial portion of the femoral ring. RESULTS: The mean operative time was 50 min (range, 20-120 min), and the length of hospital stay was 5.4 days (range, 1-29 days). During a follow-up period of 9 to 69 months, there was no recurrence, and only two complications. One of these complications was an infected mesh that occurred in a case involving cecal injury. It was treated with continuous irrigation and salvaged. The other complication was a midline wound infection after a small bowel resection for a strangulated obturator hernia. CONCLUSIONS: Familiarity with the anatomy involved leads to the conclusion that the laparoscopic approach, specifically the TEP procedure, can be used without hesitation even in cases of acutely incarcerated hernia.

Acute Disease↗
PubMed2003

Laparoscopic adjustable gastric banding: is there a learning curve?

BACKGROUND: To be certified for laparoscopic placement of adjustable gastric banding, surgeons must have advanced laparoscopic experience. Despite previous exposure to other kinds of laparoscopy, there may a learning curve specific to Lap-Band placement. METHODS: Sixty consecutive patients were prospectively separated into two groups: the first 30 patients operated on (group 1) and the second 30 patients operated on (group 2). RESULTS: Both groups were similar statistically in regard to gender, age, and body mass index. Operative time for group 1 was 79 +/- 31.1 min. There were 11 (37%) complications in 10 patients. Operative time for group 2 was 59 +/- 19.9 min. There were two complications (7%). All operations were completed laparoscopically. Operative time was significantly lower in group 2 ( t-test; p = 004). Complications were also significantly lower (chi-square; p = 0.005). The number of reoperations was also reduced and approached statistical significance (chi-square; p = 0.054). Readmissions, although reduced, were not statistically significant. There were no deaths in either group. CONCLUSIONS: Despite a surgeon's history of advanced laparoscopic experience, there is a definite learning curve associated with the laparoscopically placed adjustable gastric band.

Adult↗
PubMed2003

Normal cognition and behavior in a Smith-Lemli-Opitz syndrome patient who presented with Hirschsprung disease.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis. It is caused by mutations in the gene encoding the enzyme 7-dehydrocholesterol Delta7-reductase (DHCR7), which catalyzes the final step in cholesterol biosynthesis, usually resulting in cholesterol deficiency. We report a 3.5-year-old girl who has cognition in the low average range and normal behavior, but in whom molecular studies identified two missense mutations in DHCR7: V326L and F284L. She was born at term following an uncomplicated pregnancy and delivery, and presented at 12 days of age with poor feeding, abdominal distention, and jaundice. Colonic biopsy was consistent with Hirschsprung disease. On physical examination she had mild ptosis, a long philtrum, mild micrognathia, a short, upturned nose, and subtle 2,3 syndactyly. Her 7-dehydrocholesterol (7-DHC) level was markedly elevated at 8.7 mg/dl (normal 0.10 +/- 0.05), and her cholesterol level was normal at 61 mg/dl (normal for newborn period 50-80 mg/dl). Karyotype analysis was normal, 46,XX. Breast milk feeding was initiated and continued for 18 months. Cholesterol supplementation was implemented at 100 mg/kg/day at 3 months, which resulted in increased cholesterol levels and reduced dehydrocholesterol levels. Neuropsychological testing has shown functioning in the low average range, between the 14th and 18th centiles when compared to peers. This is markedly higher than most children with SLOS. She has no behavioral problems. MRI and MRS testing of the brain revealed no structural abnormalities. This is in contrast to a recently reported case by Prasad et al. [2002: Am J Med Genet 108:64-68] with a mild phenotype, behavioral problems, and abnormal MRI, who is compound heterozygote for both a null and missense mutation. Our case suggests that patients with severe feeding disorders with or without Hirschprung disease and postnatal onset microcephaly may warrant screening for SLOS.

Behavior↗
PubMed2003

Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer.

OBJECTIVE: To review the evidence for the use of bisphosphonates to reduce skeletal morbidity in cancer patients with bone metastases. DATA SOURCES: Electronic databases, scanning reference lists, and consultation with experts and pharmaceutical companies. Foreign language papers were included. STUDY SELECTION: Included trials were randomised controlled trials of patients with malignant disease and bone metastases who were treated with oral or intravenous bisphosphonate compared with another bisphosphonate, placebo, or standard care. All trials measured at least one outcome of skeletal morbidity. RESULTS: 95 articles were identified; 30 studies fulfilled inclusion criteria. In studies that lasted > or = 6 months, compared with placebo bisphosphonates significantly reduced the odds ratio for fractures (vertebral 0.69, 95% confidence interval 0.57 to 0.84, P < 0.0001; non-vertebral 0.65, 0.54 to 0.79, P < 0.0001; combined 0.65, 0.55 to 0.78, P < 0.0001), radiotherapy (0.67, 0.57 to 0.79, P < 0.0001), and hypercalcaemia (0.54, 0.36 to 0.81, P = 0.003) but not for orthopaedic surgery (0.70, 0.46 to 1.05, P = 0.086) or spinal cord compression (0.71, 0.47 to 1.08, P = 0.113). The reduction in orthopaedic surgery was significant in studies that lasted over a year (0.59, 0.39 to 0.88, P = 0.009). Use of bisphosphonates significantly increased time to first skeletal related event but did not increase survival. Subanalyses showed that most evidence supports use of intravenous aminobisphosphonates. CONCLUSIONS: In people with metastatic bone disease bisphosphonates significantly decrease skeletal morbidity, except for spinal cord compression and increased time to first skeletal related event. Treatment should start when bone metastases are diagnosed and continue until it is no longer clinically relevant.

Bone Neoplasms↗
PubMed2003

Acceptability and compliance with hip protectors in community-dwelling women at high risk of hip fracture.

OBJECTIVES: To determine acceptability and compliance with hip protectors in women at high risk of hip fracture who are living independently in the community. METHODS: Women aged 65 yr and over referred for open access bone densitometry who had femoral neck osteoporosis and a high risk of falling were asked to wear hip protectors. RESULTS: Eighty five women fulfilled the inclusion criteria of whom 32 (38%) found the hip protectors acceptable and agreed to participate. Reasons given by the remaining 53 (62%) for not finding the hip protectors acceptable included discomfort on wearing, dislike of their personal appearance with the hip protectors on, and disagreement about their fracture risk. Participants were more likely to have a family history of osteoporosis (47 vs 26%, respectively) and hip fracture (16 vs 8%) compared with non-participants. At 12 months only about half of the subjects were wearing hip protectors daily. CONCLUSIONS: Our findings suggest that only a minority of community-dwelling women at high risk of hip fracture will wear hip protectors to reduce fracture risk. Their use should be restricted to highly motivated women who should be carefully identified.

Accidental Falls↗
PubMed2003

hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan.

hAG-2 and hAG-3 are recently discovered human homologues of the secreted Xenopus laevis proteins XAG-1/2 (AGR-1/2) that are expressed in the cement gland, an ectodermal organ in the head associated with anteroposterior fate determination during early development. Although the roles of hAG-2 and hAG-3 in mammalian cells are unknown, both proteins share a high degree of protein sequence homology and lie adjacent to one another on chromosome 7p21. hAG-2 mRNA expression has previously been demonstrated in oestrogen receptor (ER)-positive cell lines. In this study, we have used real-time quantitative RT - PCR analysis and immunohistochemistry on tissue microarrays to demonstrate concordant expression of hAG-2 and hAG-3 mRNA and protein in breast tumour tissues. Tumour expression of both genes correlated with OR (hAG2, P=0.0002; hAG-3, P=0.0012), and inversely correlated with epidermal growth factor receptor (EGFR) (P=0.003). Yeast two-hybrid cloning identified metastasis-associated GPI-anchored C4.4a protein and extracellular alpha-dystroglycan (DAG-1) as binding partners for both hAG-2 and hAG-3, which if replicated in clinical oncology would demonstrate a potential role in tumour metastasis through the regulation of receptor adhesion and functioning. hAG-2 and hAG-3 may therefore serve as useful molecular markers and/or potential therapeutic targets for hormone-responsive breast tumours.

Amino Acid Sequence↗
PubMed2003

Regulation and function of spinal and peripheral neuronal B1 bradykinin receptors in inflammatory mechanical hyperalgesia.

Activation of either B1 or B2 bradykinin receptors by kinins released from damaged tissues contributes to the development and maintenance of inflammatory hyperalgesia. Whereas B2 agonists activate sensory neurones directly, B1 agonists were thought only to have indirect actions on sensory neurones. The recent discovery of constitutive B1 receptor expression in the rat nervous system lead us to re-investigate the role of neuronal B1 receptors in inflammatory hyperalgesia. Therefore we have examined B1 bradykinin receptor regulation in rat dorsal root ganglia in a model of inflammatory hyperalgesia, and correlated it with hyperalgesic behaviour. Twenty-four hours after injection of Freund's complete adjuvant into one hindpaw, there was a significant increase in B1 protein expression (measured by immunohistochemistry) in both ipsilateral and contralateral dorsal root ganglion neurones, whereas axotomy resulted in reduction of B1 protein in ipsilateral dorsal root ganglia. In behavioural experiments, the B1 antagonist desArg10HOE140, administered by either intrathecal or systemic routes, attenuated Freund's complete adjuvant-induced mechanical hyperalgesia in the inflamed paw, but did not affect mechanical allodynia. The B1 agonist, desArg9BK, did not affect paw withdrawal thresholds in nai;ve rats following intraplantar administration into the paw, whilst intrathecal administration elicited mechanical hyperalgesia. However, after Freund's complete adjuvant-induced inflammation, desArg9BK caused a marked mechanical hyperalgesia, by either route, of the contralateral, uninflamed hindpaw, correlating with the observed contralateral and ipsilateral increases in receptor levels. Our results suggest a functional role for B1 receptors expressed both in the periphery and in the spinal cord, in mechanical hyperalgesia during inflammation.

Animals↗
PubMed2003

Tumour thickness predicts cervical nodal metastases and survival in early oral tongue cancer.

Squamous cell carcinoma (SCC) of the oral tongue is characterized by a high propensity for cervical nodal metastasis, which affects the probability of regional control and survival. Until now, elective treatment of the clinically negative neck in early lesions (T(1-2)) of the oral tongue cancer remains controversial. This study attempted to identify predictive factor(s) for cervical nodal metastasis and treatment outcomes in patients with early stage SCC of the oral tongue treated primarily by surgery. Fifty patients with previously untreated Stage I/II primary tongue carcinomas with available archival specimens treated at the Royal Marsden Hospital between 1981 and 1998 were reviewed. Clinico-pathological features including age, gender, alcohol and tobacco consumption, tumour location, histological grade, tumour-stromal border, growth pattern, tumour thickness, and clinical stage were evaluated and the correlations with cervical metastases and outcome analysis were determined. The overall occult nodal metastatic rate was 40% (20/50). Tumour thickness exceeding 5 mm was statistically significantly correlated with cervical metastases (P = 0.003; relative risk = 2.429). No statistical correlation was observed between other clinico-pathological parameters and nodal metastasis. With a median follow-up of 98 months, 5-year actuarial overall, disease-specific (DSS), and relapse-free survival were 65.71, 67.77, and 68.18%, respectively. Univariate analysis for DSS showed poorer outcomes for patients with age > 60 years (P = 0.0423) and tumour thickness > 5 mm (P = 0.0067). The effect of tumour thickness was maintained (P = 0.005) on multivariate analysis. The present study indicates that the thickness of primary tumour has a strong predictive value for occult cervical metastasis and poor outcomes in patients with Stage I/II oral tongue SCC. Thus, elective neck treatment (surgery or irradiation) is indicated for tumours exceeding 5 mm thickness.

Adult↗
PubMed2003

Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B.

B-cell-specific plasma-membrane proteins are potential targets for either small molecule or antibody-based therapies. We have sought to annotate proteins expressed at the cell surface membrane in patients with chronic lymphocytic leukemia (CLL) using plasma-membrane-based proteomic analysis to identify previously uncharacterized and potentially B-cell-specific proteins. Proteins from plasma-membrane fractions were separated on one-dimensional gels and trypsinized fractions subjected to high-throughput MALDI-TOF mass spectrometry. Using this method, many known B-cell surface antigens were detected, but also known proteins not previously described in this disease or in this cellular compartment, including cell surface receptors, membrane-associated enzymes and secreted proteins, and completely unknown proteins. To validate the method, we show that BLK, a B-cell-specific kinase, is located in the CLL-plasma-membrane fraction. We also describe two novel proteins (MIG2B and B-cell novel protein #1, BCNP1), which are expressed preferentially in B cells. MIG2B is in a highly conserved and defined gene family containing two plasma-membrane-binding ezrin/radixin/moesin domains and a pleckstrin homology domain; the Caenorhabditis elegans homolog (UNC-112) is a membrane-associated protein that colocalizes with integrin at cell-matrix adhesion complexes. BCNP1 is a completely unknown protein with three predicted transmembrane domains, with three alternatively spliced final exons. Proteomic analysis may thus define new potential therapeutic targets.

Apoptosis Regulatory Proteins↗
PubMed2003

A clinical procedure to predict the value of temporary occlusion therapy in keratoconjunctivitis sicca.

PURPOSE: To evaluate the effects of dissolvable collagen punctal plugs on the symptoms, tear stability and volume in aqueous deficient dry eyes. METHODS: Sixty-two aqueous deficient dry eye patients of mixed aetiology underwent lacrimal punctal occlusion with dissolvable collagen plugs. The subjects were randomly allocated to one of two treatment groups: group I (n = 36) had their lower puncta occluded and group II (n = 26) had both their upper and lower puncta occluded. The effectiveness of this treatment was clinically assessed by (1). scoring subject symptoms and (2). measuring the tear parameters of tear thinning time (TTT) and tear meniscus height (TMH) as indicators of tear stability and volume, respectively. Following baseline measurements, patients were reviewed at time intervals of 5 and 12 days post-occlusion. A group of age- and gender-matched normals (n = 45) was recruited for comparison (group III). RESULTS: Tear volume and stability were significantly higher in group III compared with I and II at baseline. In the treated groups on both days 5 and 12: (1). symptom score reduced significantly from a median value of 7 to 3 (p = <0.001); (2). tear stability increased significantly from a median value of 3 to 5 s by day 5 (p <or= 0.001); reduced between days 5 and 12 (p < 0.05) and remained below the stability in group III at all times; (c). tear volume increased significantly by day 5 in both treatment groups from a median value of 0.13 to 0.20 mm (p<or=0.001), remained stable by day 12 in group II but reduced in group I (p < 0.05); (d). the increase in tear volume was negatively correlated with pre-treatment tear volume; (e). symptom score correlated with both baseline tear volume and stability. CONCLUSION: Collagen plugs improved tear status in the aqueous deficient dry eyes. Occluding both upper and lower puncta with temporary collagen plugs offers no practical beneficial gain compared with occluding just the lower punctum.

Adult↗
PubMed2003

Developmental binge exposure to ethanol and artificial rearing do not affect the social transfer of diet preference.

BACKGROUND: A previous study reported no effect of binge exposure to ethanol during the brain growth spurt on the social acquisition of enhanced diet preference in male rats. The objective of this study was to replicate this finding by using the artificial rearing technique and to investigate whether delay-dependent mnemonic deficits previously observed in the water maze would extend to social memory of diet preference. We also addressed whether this naturalistic behavior was dependent on the presentation of diet odor in the context of a rat-produced component in ethanol-exposed rats, as it is in normal controls. METHODS: Male rat pups were reared artificially from postnatal days 5 to 18, during which (postnatal days 6-9) they were fed either 6.5 g/kg/day of ethanol in a binge model or an isocaloric maltose-dextrin solution (gastrostomy controls). A third suckled control group was reared normally. These test rats were allowed to interact with conspecifics that had previously consumed a distinctive diet, X. Subsequently, the experimental rats were provided a choice between two novel diets, one of which was X, after delays of 0 hr (experiment 1), 24 hr, and 4 weeks (experiment 2). In experiment 3, the rats were again given the two-choice preference test, but after exposure to the diet odor alone. RESULTS: All groups demonstrated a significant preference for the socially cued diet in experiments 1 and 2, and the strength of this inclination remained consistent across the 0-hr, 24-hr, and 4-week retention intervals. Moreover, all groups demonstrated sensitivity to the social context of this task, as shown by a lesser preference for the diet exposed alone in experiment 3. CONCLUSIONS: Intact performance on the ethologically meaningful diet-preference test supports specificity in the cognitive/behavioral effects of developmental exposure to ethanol. Interestingly, early isolation, as experienced in the artificial-rearing procedure, also did not impair performance on this social task.

Animals↗
PubMed2003

On the sensitivity of wall stresses in diseased arteries to variable material properties.

Accurate estimates of stress in an atherosclerotic lesion require knowledge of the material properties of its components (e.g., normal wall, fibrous plaque, calcified regions, lipid pools) that can only be approximated. This leads to considerable uncertainty in these computational predictions. A study was conducted to test the sensitivity of predicted levels of stress and strain to the parameter values of plaque used in finite element analysis. Results show that the stresses within the arterial wall, fibrous plaque, calcified plaque, and lipid pool have low sensitivities for variation in the elastic modulus. Even a +/- 50% variation in elastic modulus leads to less than a 10% change in stress at the site of rupture. Sensitivity to variations in elastic modulus is comparable between isotropic nonlinear, isotropic nonlinear with residual strains, and transversely isotropic linear models. Therefore, stress analysis may be used with confidence that uncertainty in the material properties generates relatively small errors in the prediction of wall stresses. Either isotropic nonlinear or anisotropic linear models provide useful estimates, however the predictions in regions of stress concentration (e.g., the site of rupture) are somewhat more sensitive to the specific model used, increasing by up to 30% from the isotropic nonlinear to orthotropic model in the present example. Changes resulting from the introduction of residual stresses are much smaller.

Anisotropy↗