Traumatic wound rupture after penetrating keratoplasty in Africa

AIM: To investigate risk factors, visual outcome, and graft survival for traumatic wound rupture after penetrating keratoplasty. METHODS: A retrospective analysis of 336 patients who underwent penetrating keratoplasty from 1988 to 1995. RESULTS: 19 patients (5.7%) suffered traumatic postoperative wound rupture requiring surgical repair. They were younger (mean age 16.6 years, 95% CI 13.2-20.6) and more frequently keratoconic (p = 0.01) than other patients (mean age 28.9 years, 95% CI 26.-31.0). Mean postoperative follow up was 37.7 (SD 22.9) months and 24.5 (18.9) months for the rupture and non-rupture patients. Mean interval between keratoplasty and rupture was 18 (21) weeks. The lens was damaged and removed in 37% of ruptured eyes. For keratoconics, the probability of graft survival at 5 years was lower (p = 0.03) in the ruptured eyes (75%) than in the non-ruptured eyes (90%). Endothelial failure was a more common (p <0.05) cause of graft opacification in ruptured grafts than in intact grafts. Of the ruptured eyes, 53% achieved a final corrected acuity of at least 6/18 and 63% achieved at least 6/60 compared with 48% and 71% of the intact eyes respectively (both p >0.1). The proportion of keratoconic eyes which achieved at least 6/60 was lower (p = 0.02) in the ruptured eyes (67%) than the non-ruptured eyes (87%). Eyes with wound ruptures of 5 clock hours or greater were less likely (p <0.05) to achieve an acuity of 6/18 and were more likely (p <0.05) to have an associated lens injury. CONCLUSIONS: Graft rupture is relatively common in African practice, particularly in young keratoconics. Visual outcome and graft survival are not significantly worse than for other grafted eyes, but are significantly worse than for other grafted keratoconic eyes.     

Modulation by general anaesthetics of rat GABAA receptors comprised of α1β3 and β3 subunits expressed in human embryonic kidney 293 cells

1. Radioligand binding and patch-clamp techniques were used to study the actions of γ-aminobutyric acid (GABA) and the general anaesthetics propofol (2,6-diisopropylphenol), pentobarbitone and 5α-pregnan-3α-ol-20-one on rat α1 and β3 GABA_A receptor subunits, expressed either alone or in combination.
2. Membranes from HEK293 cells after transfection with α1 cDNA did not bind significant levels of [³⁵S]-tert-butyl bicyclophosphorothionate ([³⁵S]-TBPS) (<0.03 pmol mg⁻¹ protein). GABA (100 μM) applied to whole-cells transfected with α1 cDNA and clamped at −60 mV, also failed to activate discernible currents.
3. The membranes of cells expressing β3 cDNAs bound [³⁵S]-TBPS (∼1 pmol mg⁻¹ protein). However, the binding was not influenced by GABA (10 nM–100 μM). Neither GABA (100 μM) nor picrotoxin (10 μM) affected currents recorded from cells expressing β3 cDNA, suggesting that β3 subunits do not form functional GABA^A receptors or spontaneously active ion channels.
4. GABA (10 nM–100 μM) modulated [³⁵S]-TBPS binding to the membranes of cells transfected with both α1 and β3 cDNAs. GABA (0.1 μM–1 mM) also dose-dependently activated inward currents with an EC₅₀ of 9 μM recorded from cells transfected with α1 and β3 cDNAs, clamped at −60 mV.
5. Propofol (10 nM–100 μM), pentobarbitone (10 nM–100 μM) and 5α-pregnan-3α-ol-20-one (1 nM–30 μM) modulated [³⁵S]-TBPS binding to the membranes of cells expressing either α1β3 or β3 receptors. Propofol (100 μM), pentobarbitone (1 mM) and 5α-pregnan-3α-ol-20-one (10 μM) also activated currents recorded from cells expressing α1β3 receptors.
6. Propofol (1 μM–1 mM) and pentobarbitone (1 mM) both activated currents recorded from cells expressing β3 homomers. In contrast, application of 5α-pregnan-3α-ol-20-one (10 μM) failed to activate detectable currents.
7. Propofol (100 μM)-activated currents recorded from cells expressing either α1β3 or β3 receptors reversed at the C1⁻ equilibrium potential and were inhibited to 34±13% and 39±10% of control, respectively, by picrotoxin (10 μM). 5α-Pregnan-3α-ol-20-one (100 nM) enhanced propofol (100 μM)-evoked currents mediated by α1β3 receptors to 1101±299% of control. In contrast, even at high concentration 5α-pregnan-3α-ol-20-one (10 μM) caused only a modest facilitation (to 128±12% of control) of propofol (100 μM)-evoked currents mediated by β3 homomers.
8. Propofol (3–100 μM) activated α1β3 and β3 receptors in a concentration-dependent manner. For both receptor combinations, higher concentrations of propofol (300 μM and 1 mM) caused a decline in current amplitude. This inhibition of receptor function reversed rapidly during washout resulting in a ‘surge'' current on cessation of propofol (300 μM and 1 mM) application. Surge currents were also evident following pentobarbitone (1 mM) application to cells expressing either receptor combination. By contrast, this phenomenon was not apparent following applications of 5α-pregnan-3α-ol-20-one (10 μM) to cells expressing α1β3 receptors.
9. These observations demonstrate that rat β3 subunits form homomeric receptors that are not spontaneously active, are insensitive to GABA and can be activated by some general anaesthetics. Taken together, these data also suggest similar sites on GABA_A receptors for propofol and barbiturates, and a separate site for the anaesthetic steroids.

     

Long-term risk of colorectal cancer by gender after positive colonoscopy: population-based cohort study

Background: Evidence for surveillance intervals of colonoscopy are primarily based on adenoma recurrence rate rather than on colorectal cancer (C.R.C.) incidence. Little is known about long-term risk of C.R.C. after positive colonoscopy. In view of men have significantly higher C.R.C. risk than women, we aimed to estimate the gender-specific C.R.C. incidence after positive colonoscopy (adenoma or malignant lesion) at follow-up colonoscopy.

Methods: A retrospective cohort study was conducted using data from a database of colonoscopy screening and surveillance. Patients having had a colonoscopy (January 2010–March 2014) were selected as study subjects and the history of prior colonoscopies was reviewed. Multivariable Weibull regression models were used to estimate the incidence of C.R.C. at follow-up colonoscopy for subjects who were assigned a stratified risk level. The benchmark risk was defined according to a national survey.

Results: The interval incidence of C.R.C. at a 10 year follow-up was 164 (95% C.I. 63–343) and 79 (95% C.I. 26–188) per 100,000 person-years for low-risk men and women respectively, which tallied with our benchmark risk. Men exceeded the benchmark risk in 3–5 years if they had an incomplete polyp removal, ≥3 adenomas during their last colonoscopy or a personal C.R.C. history, and in 7–8 years if they only had familial C.R.C. history. Women had a lower risk of C.R.C., and reached a same risk level 3–5 years later than men. Coexisting above risk factors resulted in a sharp increase in the incidence of C.R.C. at follow-up exceeding the benchmark much earlier.

Conclusion: Surveillance intervals for men based on incidence of C.R.C. are in line with that recommended by the current guidelines for colonoscopy. However, an extension of 3–5 years may be appropriate for women. To target personalized medicine, a risk predictive model could be used to identify an appropriate surveillance interval for each individual in the future.     

Assessment of liposome bupivacaine infiltration versus continuous femoral nerve block for postsurgical analgesia following total knee arthroplasty: a retrospective cohort study

Objective: Perioperative pain management is an important aspect of recovery from total knee arthroplasty (TKA) because severe pain can delay ambulation and hospital discharge. The objective of this retrospective sequential cohort study was to determine the impact of local infiltration analgesia using liposome bupivacaine (Exparel¹) when compared with a continuous femoral nerve block (FNB) following TKA.

Methods: This retrospective cohort study included consecutive patients who underwent TKA between April 2011 and April 2014, and received one of three interventions. Study Group A received adductor canal infiltration with bupivacaine HCl and knee infiltration with liposome bupivacaine. Study Group B received adductor canal infiltration with liposome bupivacaine and knee infiltration with liposome bupivacaine. The control group received a continuous FNB with ropivacaine HCl delivered via an elastomeric pump. Numeric pain rating scores (NPRS), distance walked, length of stay (LOS), and dose of narcotic medication were the key efficacy variables of interest.

Results: A total of 237 patients were included in this study: 98 in Group A, 34 in Group B, and 105 controls. On postoperative day (POD) 0, mean (standard deviation [SD]) NPRSs were similar between Group A (1.8 [1.7]), Group B (2.7 [1.8]), and the control group (2.3 [2.4]). Significantly (p?<?0.05) more patients in Group A (58%) and Group B (44%) walked on POD0 than in the control group (0%); almost all patients walked on POD1. The mean (SD) distance walked was also significantly greater (p?<?0.05) on POD1 in Group A (193 [203] feet) and Group B (211 [144] feet) than in the control group (46 [73] feet). Mean (SD) LOS was significantly (p?<?0.05) shorter in Group B (2.2 [1.2] days), than in the control group (3.2 [0.7] days) and Group A (3.0 [1.7] days).

Conclusions: Local infiltration analgesia using liposome bupivacaine was associated with improved ambulation and shorter LOS following TKA when compared with continuous FNB in this retrospective cohort study.     

Cerebral blood flow monitoring in clinical practice

The brain depends on a continuous flow of blood to provide it with oxygen and glucose needed to maintain normal function and structural integrity, thus cerebral blood flow is normally tightly regulated. A decrease in cerebral blood flow to ischemic levels may be tolerated for only minutes to hours, depending on the severity of the ischemia. If cerebral blood flow ceases completely, brain cell death occurs within minutes. A variety of conditions are encountered clinically, such as stroke or traumatic brain injury, where an actual or potential alteration in cerebral blood flow puts the brain at risk for ischemia and infarction. In this article, the physiology of cerebral blood flow will be presented as a basis for understanding cerebral blood flow regulation and the rationale for clinical interventions to optimize cerebral blood flow. Techniques currently available to assess cerebral blood flow and clinical situations in which cerebral blood flow is measured will be discussed. Clinical interventions will be presented briefly.     

Decreased detoxification genes and genome size make the human body louse an efficient model to study xenobiotic metabolism

The human body louse, Pediculus humanus humanus, has one of the smallest insect genomes, containing ～10 775 annotated genes. Annotation of detoxification [cytochrome P450 monooxygenase (P450), glutathione‐S‐transferase (GST), esterase (Est) and ATP‐binding cassette transporter (ABC transporter)] genes revealed that they are dramatically reduced in P. h. humanus compared to other insects except for Apis mellifera. There are 37 P450, 13 GST and 17 Est genes present in P. h. humanus, approximately half the number found in Drosophila melanogaster and Anopheles gambiae. The number of putatively functional ABC transporter genes in P. h. humanus and Ap. mellifera are the same (36) but both have fewer than An. gambiae (44) or Dr. melanogaster (65). The reduction of detoxification genes in P. h. humanus may be a result of this louse's simple life history, in which it does not encounter a wide variety of xenobiotics. Neuronal component genes are highly conserved across different insect species as expected because of their critical function. Although reduced in number, P. h. humanus still retains at least a minimum repertoire of genes known to confer metabolic or toxicokinetic resistance to xenobiotics (eg Cyp3 clade P450s, Delta GSTs, B clade Ests and B/C subfamily ABC transporters), suggestive of its high potential for resistance development.     

Increased phosphatidylcholine concentration in saliva reduces surface tension and improves airway patency in obstructive sleep apnoea

Surface tension may have important role for maintaining upper airway patency in patients with obstructive sleep apnoea. It has been demonstrated that elevated surface tension increases the pharyngeal pressures required to reopen the upper airway following collapse. The aim of the study was to evaluate the associations between the concentrations of endogenous surfactants in saliva with indices of upper airway patency in obstructive sleep apnoea. We studied 20 male patients with obstructive sleep apnoea (age: 60·3 ± 10·3 years; BMI: 25·9 ± 4·6 kg m^?2; AHI: 41·5 ± 18·6 events h^?1). We obtained 100‐μL samples of saliva prior to overnight polysomnographic sleep study. The surface tension was determined using the pull‐off force technique. The concentration of phosphatidylcholine (PC) was evaluated by liquid chromatography‐mass spectrometry (LC‐MS/MS). Regression analysis between apnoea, hypopnoea and apnoea/hypopnoea indices and the ratio of hypopnoea time/total disordered breathing time (HT/DBT) with surface tension and PC were performed. P < 0·05 was considered significant. The mean saliva surface tension was 48·8 ± 8·0 mN m^?1 and PC concentration was 15·7 ± 11·1 nM. The surface tension was negatively correlated with the PC concentration (r = ?0·48, P = 0·03). There was a significant positive correlation between surface tension with hypopnoea index (r = 0·50, P = 0·03) and HT/DBT (r = 0·6, P = 0·006), but not apnoea or apnoea/hypopnoea index (P > 0·11). Similarly, PC concentration negatively correlated with hypopnoea index (r = ?0·45, P = 0·04) and HT/DBT (r = ?0·6, P = 0·004), but not with apnoea index or AHI (P > 0·08). An increase in salivary PC concentration may increase upper airway patency in obstructive sleep apnoea through a reduction in surface tension.     

Extensive and breed-specific linkage disequilibrium in Canis familiaris

The 156 breeds of registered dogs in the United States offer a unique opportunity to map genes important in disease susceptibility, morphology, and behavior. Linkage disequilibrium (LD) is of current interest for its application in whole genome association mapping, since the extent of LD determines the feasibility of such studies. We have measured LD at five genomic intervals, each 5 Mb in length and composed of five clusters of sequence variants spaced 800 kb-1.6 Mb apart. These intervals are located on canine chromosomes 1, 2, 3, 34, and 37, and none is under obvious selective pressure. Approximately 20 unrelated dogs were assayed from each of five breeds: Akita, Bernese Mountain Dog, Golden Retriever, Labrador Retriever, and Pekingese. At each genomic interval, SNPs and indels were discovered and typed by resequencing. Strikingly, LD in canines is much more extensive than in humans: D' falls to 0.5 at 400-700 kb in Golden Retriever and Labrador Retriever, 2.4 Mb in Akita, and 3-3.2 Mb in Bernese Mountain Dog and Pekingese. LD in dog breeds is up to 100x more extensive than in humans, suggesting that a correspondingly smaller number of markers will be required for association mapping studies in dogs compared to humans. We also report low haplotype diversity within regions of high LD, with 80% of chromosomes in a breed carrying two to four haplotypes, as well as a high degree of haplotype sharing among breeds.