Anion gap among patients of multiple myeloma and normal individuals

OBJECTIVE: To compare the Anion gap between patients of multiple myeloma and normal individuals presenting at a tertiary care hospital. DESIGN AND METHODS: This is a matched case-control study conducted at Aga Khan University Hospital, Karachi, from July 10, 2004 to April 30, 2006. The anion gap (AG) from the medical records of the 82 diagnosed cases of multiple myeloma (MM) and 104 controls were compared. Immunoglobulins (IgG and IgA) were measured by array nephelometric assay. Staging for MM patients were performed based on Salmon-Durie method. AGs were compared by independent sample t-test. Pearson coefficient of correlation was used to correlate paraprotein IgG concentration and anion gap. RESULTS:: Of the 186 study subjects (82 cases and 104 controls), 70% were males and 30% were females. The mean ages of MM and controls were 59.68+/-11.94 and 60+/-9.2 years respectively. There was a significant difference in mean AG, 11.2+/-1.7 mmol/L in control group (p<0.001) compared to 6.8+/-4.6 mmol/L for IgG MM and 8.4+/-4.37 mmol/L for IgA MM patients. Multiple myeloma patients stratified by clinical stages had anion gap of 8.7+/-1.7 in stage I, 7.93+/-0.47 in stage II and 5.65+/-0.31 in stage III. A significant correlation was found in IgG myeloma when anion gap was expressed as a function of the serum monoclonal protein concentration. CONCLUSION: The anion gap is significantly lower in multiple myeloma patients compared to controls. Lowered anion gap is more specific feature of the IgG type MM. We suggest that correlation of AG with the disease severity and with paraproteins concentration could potentially be useful in monitoring patients for disease progression. However, longitudinal studies are required to confirm the utility of anion gap in monitoring patients with MM.     

CYP1B1 mutation profile of Iranian primary congenital glaucoma patients and associated haplotypes

The mutation spectrum of CYP1B1 among 104 primary congenital glaucoma patients of the genetically heterogeneous Iranian population was investigated by sequencing. We also determined intragenic single nucleotide polymorphism (SNP) haplotypes associated with the mutations and compared these with haplotypes of other populations. Finally, the frequency distribution of the haplotypes was compared among primary congenital glaucoma patients with and without CYP1B1 mutations and normal controls. Genotype classification of six high-frequency SNPs was performed using the PHASE 2.0 software. CYP1B1 mutations in the Iranian patients were very heterogeneous. Nineteen nonconservative mutations associated with disease, and 10 variations not associated with disease were identified. Ten mutations and three variations not associated with disease were novel. The 13 novel variations make a notable contribution to the approximately 70 known variations in the gene. CYP1B1 mutations were identified in 70% of the patients. The four most common mutations were G61E, R368H, R390H, and R469W, which together constituted 76.2% of the CYP1B1 mutated alleles found. Six unique core SNP haplotypes were identified, four of which were common to the patients with and without CYP1B1 mutations and controls studied. Three SNP blocks determined the haplotypes. Comparison of haplotypes with those of other populations suggests a common origin for many of the mutations.     

Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery.

The main objective of this study was to develop and characterize a pH-sensitive biodegradable polymeric nanoparticulate system for tumor-selective paclitaxel delivery. A representative hydrophobic poly(beta-amino ester) (poly-1) was synthesized by conjugate addition of 4,4'-trimethyldipiperidine with 1,4-butanediol diacrylate. Poly-1 (M(n) 10,000 daltons) nanoparticles were prepared by the controlled solvent displacement method in an ethanol-water system in the presence of Pluronic) F-108, a poly(ethylene oxide) (PEO)-containing non-ionic surfactant. Control and PEO-modified nanoparticles were characterized by Coulter counter, scanning electron microscopy (SEM), zeta potential measurements, and electron spectroscopy for chemical analysis (ESCA). Polymer degradation studies were performed in phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C. Paclitaxel loading capacities and efficiencies were determined and release studies were performed in Tween)-80 (0.1%, w/v)-containing PBS at 37 degrees C. Control and PEO-modified nanoparticles, labeled with rhodamine-123, were incubated with BT-20 cells to examine the uptake and cellular distribution as a function of time. PEO-modified nanoparticles with an average size of 100-150 nm and a positive surface charge of 37.0 mV were prepared. SEM analysis showed distinct smooth, spherical particles. The ether (-C-O-) peak of the C(1s) envelope in ESCA confirmed the surface presence of PEO chains. Polymer biodegradation studies showed that almost 85% of the starting material degraded after 6 days. The maximum paclitaxel loading efficiency attained was 97% at 1.0% (w/w) of the drug. Paclitaxel release studies showed that approximately 10% was released in the first 24 h, 80% after 3 days, and the entire content was released in approximately 5 days. After 1 h of incubation, a large fraction of the administered control and PEO-modified poly-1 nanoparticles was internalized in BT-20 cells. Results of this study demonstrate that PEO-modified poly-1 nanoparticles could provide increased therapeutic benefit by delivering the encapsulated drug to solid tumors.     

Limberg flap in management of pilonidal sinus disease: systematic review and a local experience

Objectives: To review published evidence of Limberg flap (LF) use in pilonidal sinus disease (PSD). We also included our local experience of LF.

Methods: Medline and Embase database were searched for the words ‘pilonidal, sinus, Limberg, flap’. Non-English articles and those not-related to our scope of search were omitted. We included a retrospective study of patients underwent LF in our district hospital. Data including length of hospital stay, post-operative complications and recurrence were collected.

Results: Literature review revealed 68 studies (22 case series, 35 comparative studies, nine RCTs and two meta-analyses). Recurrence rate was 0–7.4% in case series. Recurrence rate in comparative studies was 0–8.3%, compared to 4–37.7% for primary closure and 0–11% for Karydakis flap. RCTs showed that LF or its modification is superior to primary closure, with comparable results to Karydakis flap. About 26 patients included in the cohort study (16 male, average age 27 years). Six patients presented with recurrent disease. Post-operative length of hospital stay was four to seven days. Post-operative complication rate was 11.5% – [two partial wound dehiscence, one wound infection]. Recurrence rate was 7.7%. Average follow-up was 18 months.

Conclusions: Limberg flap presents a safe and effective method that can be offered for patients with primary or recurrent PSD.     

Clinical and Pathologic Characteristics of Pulmonary Carcinoid Tumors in Central and Peripheral Locations

Pulmonary carcinoid tumors occur in both central and peripheral locations, and some differences in clinico-pathological features have long been observed. We investigated a large number of resected carcinoid tumors with the aim to further define the characteristics of tumors from both locations. One hundred sixty-six resected carcinoid tumors of the lung were analyzed for a variety of clinical and pathologic features, including histology subtype, mitotic rate, Ki67 index, necrosis, invasive pattern, architectural pattern, cell morphology, sustentacular cells, neuroendocrine hyperplasia, and orthopedia homeobox protein (OTP) and TTF-1 immunohistochemical expressions. Unsupervised hierarchical cluster analysis suggested three clusters as the best solution using TTF-1 and OTP expression: TTF-1-positive and OTP-positive tumors as cluster 1, TTF-1-positive but OTP-negative as cluster 2, and TTF-1-negative and OTP-negative as cluster 3. Cluster 1 was characterized by peripheral location, presence of spindle cell component, presence of sustentacular cells, female predominance, and strong association with neuroendocrine hyperplasia. Cluster 2 was characterized by central location, polygonal cell morphology, acinar growth pattern in a subset of tumors, and only rare association with neuroendocrine hyperplasia. Cluster 3 consisted of more aggressive tumors with more heterogeneous pathologic features. Tumors showed polygonal cell morphology and acinar growth pattern. Occurrence of neuroendocrine hyperplasia was exceptional. Our study confirmed distinct characteristics of central and peripheral type carcinoid. An important difference was a strong association of the peripheral tumor with neuroendocrine hyperplasia while such an association in central tumors was negligible. The tumor location might be relevant for pathobiology of lung carcinoid tumors.     

Range–Angle-Dependent Beamforming for Cognitive Antenna Array Radar with Frequency Diversity

The inspiration behind a basic cognitive radar is the analogy between human brain and radar signal processing techniques. In this paper, we propose a hybrid model of cognitive frequency diverse array radar with adaptive range–angle-dependent beamforming. Cognitive radar properties have been incorporated to enhance the signal to interference plus noise ratio and detection capability. The proposed receiver estimates the current and future target position and tunnels this information to the transmitter as feedback. Since frequency diverse array uses a small frequency increment across the antenna elements to generate a range–angle-dependent beam pattern, the proposed scheme provides an analytical formula to compute this frequency increment based on the feedback. This saves a lot of power and reduces computational complexity. In addition, the electromagnetic pollution of environment is decreased. Monte Carlo-based simulation results have been provided to validate the performance.     

Is the management of dog bite wounds evidence based? A postal survey and review of the literature.

OBJECTIVES: To determine current practice in the management of dog bite wounds with regard to the use of prophylactic antibiotics and primary closure and to compare the available evidence. METHODS: We conducted a national postal survey of Accident and Emergency (A and E) departments in the UK to ascertain the current practice in the management of recent dog bite wounds. A questionnaire was designed and posted to a named A and E consultant. Non-respondents were sent a single reminder 8 weeks after the initial mailing. A detailed literature search was carried out using Medline, Embase and Cochrane databases to look at the available evidence. RESULTS: The postal survey yielded an 80% response. Prophylactic antibiotics were routinely used by 53% of the respondents. Although 99% of the respondents were happy to close facial dog bite lacerations, 60% were reluctant to suture other body regions. Recent available evidence suggests that restricting the use of prophylactic antibiotics for high-risk dog bite wounds and the primary suturing of appropriate dog bite lacerations is safe. CONCLUSIONS: The management of recent dog bite wounds is not entirely evidence based in many A and E departments in the UK.     

SARS-CoV-2, surgeons and surgical masks

The exact risk association of coronavirus disease 2019 (COVID-19) for surgeons is not quantified which may be affected by their risk of exposure and individual factors. The objective of this review is to quantify the risk of COVID-19 among surgeons, and explore whether facemask can minimise the risk of COVID-19 among surgeons. A systematised review was carried out by searching MEDLINE to locate items on severe acute respiratory syndrome coronavirus 2 or COVID-19 in relation to health care workers (HCWs) especially those work in surgical specialities including surgical nurses and intensivists. Additionally, systematic reviews that assessed the effectiveness of facemask against viral respiratory infections, including COVID-19, among HCWs were identified. Data from identified articles were abstracted, synthesised and summarised. Fourteen primary studies that provided data on severe acute respiratory syndrome coronavirus 2 infection or experience among surgeons and 11 systematic reviews that provided evidence of the effectiveness of facemask (and other personal protective equipment) were summarised. Although the risk of COVID-19 could not be quantified precisely among surgeons, about 14% of HCWs including surgeons had COVID-19, there could be variations depending on settings. Facemask was found to be somewhat protective against COVID-19, but the HCWs’ compliance was highly variable ranging from zero to 100%. Echoing surgical societies’ guidelines we continue to recommend facemask use among surgeons to prevent COVID-19.     

Physicochemical Characterization of Complex Drug Substances: Evaluation of Structural Similarities and Differences of Protamine Sulfate from Various Sources

The purpose of this study was to characterize and evaluate differences of protamine sulfate, a highly basic peptide drug, obtained from five different sources, using orthogonal thermal and spectroscopic analytical methods. Thermogravimetric analysis and modulated differential scanning calorimetry showed that all five protamine sulfate samples had different moisture contents and glass transition and melting temperatures when temperature was modulated from 25 to 270°C. Protamine sulfate from source III had the highest residual moisture content (4.7 ± 0.2%) at 105°C, resulting in the lowest glass transition (109.7°C) and melting (184.2°C) temperatures compared with the other four sources. By Fourier-transform infrared (FTIR) spectroscopy, the five sources of protamine sulfate had indistinguishable spectra, and the spectra were consistent with a predominantly random coil conformation in solution and a minor population in a β-sheet conformation (~12%). Circular dichroism spectropolarimetry confirmed the FTIR results with prominent minima at 206 nm observed for all five sources. Finally, proton ((1)H) nuclear magnetic resonance spectroscopy showed that all five protamine sulfate sources had identical spectra with backbone amide chemical shifts between 8.20 and 8.80 ppm, consistent with proteins with predominantly random coil conformation. In conclusion, thermal analyses showed differences in the thermal behavior of the five sources of protamine sulfate, while spectroscopic analyses showed the samples had a predominantly random coil conformation with a small amount of β-sheet present.