Cardiovascular complications and its relationship with functional outcomes in Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) is a monophasic disease characterized by acute polyradiculoneuropathy. AIM: This study investigated cardiovascular complications in patients with GBS and their relationship with outcomes. DESIGN AND METHODS: We included 96 patients, who were diagnosed with GBS according to Brighton case definitions. All enrolled patients were evaluated according to a predetermined algorithm, which included nerve conduction studies, cerebrospinal fluid analysis, electrocardiography, 2D echo, cardiac markers and autonomic function testing. RESULTS: We enrolled a total of 96 patients. The mean age of patients was 35.75 ± 17.66 years. Furthermore, 54.2% of patients developed cardiovascular complications, of which changes in electrocardiography (ECG) findings (50%), hypertension (28.12%), labile hypertension (12.5), tachycardia (26.04), bradycardia (13.54%) and a fluctuating heart rate (HR) (11.46) were common. Other cardiovascular complications seen in GBS patients were increased pro-BNP (26.04%), raised troponin T levels (3.12%), acute coronary syndrome (2.08%), heart failure (2.08%) and abnormal 2D echo findings (8.33%). The results of the univariate analysis revealed that a history of preceding infection, a Medical Research Council sum score, neck muscle weakness, facial nerve involvement, bulbar involvement, respiratory failure, cardiovascular complications, autonomic dysfunction, acute motor sensory axonal neuropathy subtype and baseline Hughes score were significantly (P < 0.005) associated with poor outcomes. However, none of these factors were found to be independently associated with poor outcomes in the multivariate analysis. CONCLUSION: A considerable number of patients with GBS developed cardiovascular complications and it needs attention.

Predicting gas phase entropy of select hydrocarbon classes through specific information-theoretical molecular descriptors.

The usefulness of five specific information-theoretical molecular descriptors was investigated for predicting the gas phase entropy of selected classes of acyclic and cyclic compounds. Among them, total information on atomic number (TIZ), graph vertex complexity (HV) and total information on bonds (TIBAT), considered together showed the best correlation along with a low standard deviation (r2 = 0.97, s = 21.14) with gas phase entropy values of 130 compounds. The multiple regression equation treating these three indices as independent variables was statistically highly significant which was evident from the F-statistics. In particular, very small difference between r2 and r2-pred values indicates that the regression model is not overfitted and is, therefore, suitable for prediction purposes. When truly used as a training set to predict (from regression equation) 40 additional compounds we get a very high correlation (r2 = 0.975), which remains almost identical (r2 = 0.97) for the combined data set of 170 compounds. The three indices appear to be useful descriptors producing correlation that remains stable with the change in the size of the data set. Also, the information-theoretical measures appear to capture an additive-cum-constitutive nature of gas phase entropy yielding an acceptable statistical fit.

Video assisted thoracoscopic thyroidectomy for retrosternal goitre.

INTRODUCTION: Thyroidectomy for retrosternal goitre is usually carried out through a cervical incision. Around 4-12% of patients, however, require an extracervical approach, usually by sternotomy. Anatomically, the thyroid extends deep behind the great vessels in the pretracheal fascia. A sternotomy is therefore not only a substantial incision but this anterior approach is also not ideal for exposure. We report the use of video assisted thoracoscopic surgery (VATS) instead of a sternotomy or thoracotomy in conjunction with a transverse cervical incision for these patients. METHODS: A retrospective descriptive study was carried out of seven patients with retrosternal goitre who underwent a VATS thyroidectomy. RESULTS: Twenty-one patients with retrosternal goitre were referred to our institution for surgical excision with the anticipation of requiring an extracervical incision. Of these, seven (median age: 68 years, range: 58-73 years) underwent a VATS thyroidectomy. The median operating time was 218 minutes (range: 120-240 minutes). The median diameter of the retrosternal goitre was 70 mm (range: 40-145 mm). Only one patient required conversion to a manubriotomy to deliver the bulky thyroid and one patient suffered a transient right recurrent laryngeal nerve palsy. The median postoperative pain scores for days 0 and 1 were 1 (range: 0-5) and 0 (range: 0-3) respectively. The median length of stay was 5 days (range: 3-7 days). CONCLUSIONS: The use of VATS in thyroidectomy for retrosternal goitre offers a minimally invasive approach resulting in less morbidity while affording excellent exposure.

In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring.

BACKGROUND: In patients with advanced ovarian cancer (OvCa), microscopic residual tumour nodules that remain after surgical debulking frequently escape detection by current treatment assessment methods and lead to disease recurrence. The aim of this study was to evaluate the use of high-resolution fibre-optic fluorescence imaging of the clinically approved photodynamic therapy (PDT) agent benzoporphyin-derivative monoacid ring A (BPD-MA) for detection of microscopic OvCa and for monitoring treatment response. METHODS: Our fluorescence microendoscope consists of a flexible imaging fibre coupled to a custom epi-fluorescence system optimised for imaging BPD-MA, which, after a single administration, serves as both an imaging agent and a light-activated therapeutic agent. After characterisation in an in vitro OvCa 3D model, we used the flexible imaging fibre to minimally invasively image the peritoneal cavity of a disseminated OvCa murine model using BPD-MA administered intraperitoneally (i.p.). To evaluate longitudinal changes in response to treatment, we compared sets of images obtained before and after PDT with those from untreated mice imaged at the same time points. RESULTS: By comparison with histopathology, we report an 86% sensitivity for tumour detection in vivo using the microendoscope. Using a custom routine to batch process-image data in the monitoring study, treated mice exhibited an average decrease of 58.8% in tumour volumes compared with an increase of 59.3% in untreated controls (P<0.05). CONCLUSIONS: Our findings indicate the potential of this approach as a reporter of treatment outcome that could aid in the rational design of strategies to mitigate recurrent OvCa.

Pegylation of charged polymer-photosensitiser conjugates: effects on photodynamic efficacy.

Conjugates between photosensitisers (PS) and charged polymeric carriers are under investigation for photodynamic therapy of cancer and may allow targeting to certain cell types or compartments in tumours. Covalent attachment of polyethylene glycol to macromolecules (pegylation) may alter their pharmacokinetics, cell type targeting, and photophysical properties. Macrophages may take up large amounts of aggregated PS, thus lessening the selectivity for cancer cells in tumours. We investigated the effect of pegylation on the uptake and phototoxicity of poly-L-lysine chlorin(e6) conjugates with either cationic or anionic charges in two cell lines, human ovarian cancer cells and mouse macrophages. The cationic conjugate after pegylation became less aggregated, consumed less oxygen and had reduced cellular uptake. However, the phototoxicity corrected for cellular uptake increased three- to five-fold. In contrast, the anionic succinylated conjugate on pegylation became more aggregated, consumed similar amounts of oxygen, and had higher cellular uptake. The anionic conjugate showed the highest relative phototoxicity towards both the cell lines (compared to the other three conjugates) and it decreased most towards the macrophages after pegylation. Pegylation reduced the amount of oxygen consumed per chlorin(e6) molecule when photosensitised cells were illuminated. These in vitro studies suggest that pegylation alters the phototoxicity of PS conjugates depending on the effect produced on the aggregation state.

The prevalence of silent kidney stones--an ultrasonographic screening study.

OBJECTIVE: Silent and not yet discovered stones of the upper urinary tract are potentially dangerous, since in due course they may cause infection, obstruction and renal damage. The aim of this study was to determine the prevalence of such silent kidney stones in a representative Pakistani population of Karachi. SUBJECTS AND METHODS: We studied 201 consecutive subjects at our hospital who underwent additional kidney screening whilst undergoing abdominal ultrasound. All these subjects did not have a history or symptoms of urolithiasis. RESULT: We found silent kidney stones in 3% of subjects. All stone bearers were males. Most stones were in the left kidney. Notably, multiple stones and stones of a considerable size went unnoticed. CONCLUSION: In addition to the usual figures of incidence and prevalence of stone disease drawn from patient data, there is a prevalence of 3% silent stones that may only be discovered incidentally or by screening. This is true for a "'stone country" like Pakistan. Figures for other regions have yet to be determined. Due to socioeconomic reasons, we believe that a general kidney screening for urolithiasis is, however, not indicated, at least in our country.

Pegylation of a chlorin(e6) polymer conjugate increases tumor targeting of photosensitizer.

Photodynamic therapy is emerging as a viable modality for the treatment of many cancers. A limiting factor in its use against intracavity tumors such as disseminated ovarian cancer is insufficient selectivity of the photosensitizer for tumor compared with normal tissue. We report on an approach to improve tumor targeting by exploiting differences between cell types and by chemical modification of a photosensitizer conjugate. Attachment of polyethylene glycol (pegylation) to a polyacetylated conjugate between poly-l-lysine and chlorin(e6) increased the relative phototoxicity in vitro toward an ovarian cancer cell line (OVCAR-5) while reducing it toward a macrophage cell line (J774), compared with the nonpegylated conjugate. Surprisingly, the increased phototoxicity of the pegylated conjugate correlated with reduced oxygen consumption. Pegylation also reduced the tendency of the conjugate to aggregate and reduced the consumption of oxygen when the conjugates were illuminated in solution in serum containing medium, suggesting a switch in photochemical mechanism from type II (singlet oxygen) to type I (radicals or electron transfer). Pegylation led to more mitochondrial localization as shown by confocal fluorescence microscopy in OVCAR-5 cells, and, on illumination, produced a switch in cell death mechanism toward apoptosis not seen with J774 cells. Conjugates were injected i.p. into nude mice bearing i.p. OVCAR-5 tumors, and the pegylated conjugate gave higher amounts of photosensitizer in tumor and higher tumor:normal tissue ratios and increased the depth to which the chlorin(e6) penetrated into the peritoneal wall. Taken together, these results suggest that pegylation of a polymer-photosensitizer conjugate improves tumor-targeting and may increase the efficacy of photodynamic therapy for ovarian cancer.

Biodistribution of charged 17.1A photoimmunoconjugates in a murine model of hepatic metastasis of colorectal cancer.

Optimizing photodynamic therapy involves attempting to increase both the absolute tumour content of photosensitizer and the selectivity between tumour and surrounding normal tissue. One reason why photodynamic therapy has not been considered suitable for treatment of metastatic tumours in the liver, is the poor selectivity of conventional photosensitizers for tumour compared to normal liver. This report details an alternative approach to increasing this selectivity by the use of antibody-targeted photosensitizers (or photoimmunoconjugates) to target intrahepatic tumours caused by human colorectal cancer cells in the nude mouse, and explores the role of molecular charge on the tumour-targeting efficiency of macromolecules. The murine monoclonal antibody 17.1A (which recognizes an antigen expressed on HT 29 cells) was used to prepare site-specific photoimmunoconjugates with the photosensitizer chlorine6. The conjugates had either a predominant cationic or anionic charge and were injected i.v. into tumour-bearing mice. Biodistribution 3 or 24 h later was measured by extraction of tissue samples and quantitation of chlorine6 content by fluorescence spectroscopy. The photoimmunoconjugates were compared to the polylysine conjugates in an attempt to define the effect of molecular charge as well as antibody targeting. The anionic 17.1A conjugate delivered more than twice as much photosensitizer to the tumour at 3 h than other species (5 times more than the cationic 17. 1A conjugate) and had a tumour:normal liver ratio of 2.5. Tumour-to-liver ratios were greater than one for most compounds at 3 h but declined at 24 h. Tumour-to-skin ratios were high (> 38) for all conjugates but not for free chlorine6. Cationic species had a high uptake in the lungs compared to anionic species. The photoimmunoconjugates show an advantage over literature reports of other photosensitizers, which can result in tumour:normal liver ratios of less than 1.

Experimental photoimmunotherapy of hepatic metastases of colorectal cancer with a 17.1A chlorin(e6) immunoconjugate.

Photoimmunotherapy (using a monoclonal antibody-targeted photosensitizer and red light) may be a strategy to overcome the limitations inherent in photodynamic therapy of liver tumors. The aims of this study were (a) to test the efficacy of selective treatment of hepatic metastases of colorectal cancer in an orthotopic murine xenograft using the murine monoclonal antibody 17.1A conjugated to the photosensitizer chlorin(e6), and (b) to compare the tumor response after the same light dose was delivered at two different fluence rates. Based on previous biodistribution studies that had shown that the photoimmunoconjugate with a polyanionic charge had both a higher absolute tumor chlorin(e6) content and a greater tumor:normal liver ratio than those obtained with a photoimmunoconjugate bearing a polycationic charge, mice were treated 3 h after i.v. injection of the polyanionic 17.1A chlorin(e6) conjugate or unconjugated photosensitizer. Red light was delivered into the liver tumor by an interstitial fiber, and tumor response end points were total tumor weight in the short term and survival in the long term. There was a highly significant reduction (<20% of controls; P = 0.0035) in the weight of the tumors in the mice treated with photoimmunotherapy, and the median survival increased from 62.5 to 102 days (P = 0.015). Photodynamic therapy with free chlorin(e6) produced a smaller decrease in tumor weight and a smaller extension of survival, neither of which were statistically significant. A comparison of photoimmunotherapy with 10 J of light delivered at 30 or 300 mW showed that the higher fluence rate prolonged survival significantly more than the lower fluence rate. This may have been because the high fluence rate gave a contribution of laser-induced hyperthermia to the photodamage. Correlation studies showed that the amount of normal liver remaining at necropsy correlated best with survival. Photoimmunotherapy shows efficacy in destroying liver tumors, and future studies should maximize selectivity to minimize the destruction of normal liver.

Ultrasonographic renal size in individuals without known renal disease.

OBJECTIVE: In order to establish some preliminary data of our population, we determined the ultrasonographic kidney dimensions in individuals without known renal disease. We assessed whether age, sex, side, body mass index (BMI) and presence or absence of diabetes mellitus and hypertension affect the renal size. METHODS: Ultrasonographic kidney measurements were performed on 194 adult patients without known kidney lesions. Measurements included length, width, cortical thickness and estimation of renal size which was obtained by multiplying the first three variables. The effect of age, gender, side, height, weight, BMI, hypertension and diabetes mellitus was statistically analyzed. RESULTS: The mean kidney length was 10.4 +/- 0.8 cm, mean with 4.5 +/- 0.6 cm and mean cortical thickness 1.6 +/- 0.2 cm. The estimated mean renal size was 76 +/- 22 cm3. Kidney length did not significantly differ between right and left, however, kidney width, cortical thickness and size did (p < 0.05). Right kidneys were smaller than the left ones. In univariate analysis, the mean renal size correlated with age, sex, side, BMI and absence or presence of hypertension and diabetes mellitus. In a multivariate analysis, however, the only significant factors affecting renal size were sex and BMI. CONCLUSION: We conclude that renal size is related to age, side, sex and the individual's height and weight. Population-based studies are needed to establish the normal values for the Pakistani population.

Intraperitoneal photoimmunotherapy of ovarian carcinoma xenografts in nude mice using charged photoimmunoconjugates.

OBJECTIVE: The objective of this study was to compare the efficacy of photoimmunoconjugates with cationic and anionic molecular charges on intraperitoneal photoimmunotherapy of ovarian cancer xenografts in nude mice. METHODS: The photosensitizer chlorin(e6) (c(e6)) was conjugated via a poly-l-lysine linker to the F(ab')(2) fragment of the murine anti-ovarian cancer monoclonal antibody OC125, resulting in a photoimmunoconjugate with a pronounced cationic charge. Alternatively, by succinylating the poly-l-lysine conjugate, a photoimmunoconjugate with a pronounced anionic charge was obtained. A murine model of ovarian cancer derived from intraperitoneal inoculation of NIH:OVCAR-5 cells was employed. The conjugate was injected intraperitoneally followed after 3 h by red light delivered through a fiber into the peritoneal cavity. These photoimmunotherapy treatments were repeated three times, and the results obtained with the anionic and cationic photoimmunoconjugates were compared with those obtained with free c(e6) and control. The extent of residual macroscopic disease and death from disease were the evaluable outcomes for tumoricidal and survival studies, respectively. RESULTS: In contrast to other intraperitoneal photosensitizers, mice showed no systemic toxicity or morbidity from the treatment. In this initial study the mean residual tumor weights in all treatment groups ranged from 33 to 73 mg, as compared with 330 mg in untreated controls (P < 0.0001), and the response to the cationic conjugate was significantly better than that to the anionic conjugate or free c(e6) (P < 0.005). The median survival for mice treated with cationic photoimmunoconjugate was 41 days, compared with 35 days in controls (P = 0.009). CONCLUSION: Photoimmunotherapy with a cationic photoimmunoconjugate produces results superior to those obtained with an anionic conjugate, and further optimization of the treatment regimen may lead to a potential treatment for advanced ovarian cancer.

Feticide followed by successful removal of pregnancy products in early abdominal pregnancy.

Patient presented with an acute abdomen at 18 weeks gestation. Ultrasound and CT scan confirmed single extra uterine gestation. Considering the maternal hazards associated with surgical removal of viable abdominal pregnancy feticide was performed with ultrasound guided intracardial injection of KCl solution. Ten days after the procedure successful removal of pregnancy was achieved with no intra or post operative complications.

Effectiveness of percutaneous nephrostomy in reversing obstructive renal failure.

A retrospective analysis of 34 patients of obstructive renal failure, initially managed by percutaneous nephrostomy was performed. Pre procedure blood biochemical profile was compared with upto one week follow-up of blood chemistry. There was a decline of 71.1% and 56.08% (P-values 0.0001 and 0.0028) in the mean values of serum creatinine and blood urea nitrogen respectively at 7 days after the procedure. Improvement in blood biochemical profile was solely dependent on performance of percutaneous nephrostomy.