Topical antiviral and antifungal medications in pregnancy: a review of safety profiles.

Medications should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Compared to oral or parenteral agents, topical medications have limited systemic absorption and are deemed safer. However, their safety profile must be assessed cautiously due to the limited available data. In this article, we aggregate human and animal studies to provide recommendations on utilizing topical antiviral and antifungal medications in pregnancy. For antiviral medications, acyclovir and trichloroacetic acid are safe to use in pregnancy. Docosanol, imiquimod and penciclovir are likely safe, but should be utilized as second-line agents. Podofilox and podophyllin resin should be avoided. For antifungal medications, clotrimazole, miconazole and nystatin are considered first-line agents. Butenafine, ciclopirox, naftifine, oxiconazole and terbinafine may be utilized after the above agents. Econazole should be avoided during the first trimester and used sparingly during 2nd and 3rd trimester. Ketoconazole and selenium sulphide are likely safe, but should be employed in limited areas for brief periods.

Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199).

Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma. In CLL, duvelisib monotherapy is associated with high iwCLL (International Workshop on Chronic Lymphocytic Leukemia) and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene expression studies (RNAseq, Nanostring, Affymetrix array and real-time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes. In concert with induction of transcript levels, reverse phase protein arrays and immunoblots confirmed increase at the protein level. The BCL2 inhibitor venetoclax induced greater apoptosis in ex vivo-cultured CLL cells obtained from patients on duvelisib compared with pre-treatment CLL cells from the same patients. In vitro combination of duvelisib and venetoclax resulted in enhanced apoptosis even in CLL cells cultured under conditions that simulate the tumor microenvironment. These data provide a mechanistic rationale for testing the combination of duvelisib and venetoclax in the clinic. Such combination regimen (NCT02640833) is being evaluated for patients with B-cell malignancies including CLL.

Safety of training and assessment in operating theatres--a systematic review and meta-analysis.

OBJECTIVE: Procedural outcomes can be used to assess the performance of specialists and trainees. This article establishes a systematic evidence base for the safety of training in the operating theatre. It also explores the possibility of using early, intermediate and late procedural outcomes of cardiac surgical operations to evaluate the performance of the clinicians and the healthcare system. METHODS: Medline, EMBASE and PsycINFO databases were searched. Comparative studies evaluating quality indicators of cardiac surgical procedures (coronary artery bypass grafting (CABG) and valve surgery) were included. guidelines from the preferred reporting items for systematic reviews and meta-analyses (PRISMA) were used. RESULTS: Fourteen studies met the inclusion criteria. For CABG, meta-analysis of outcomes did not show any significant differences between the technical and non-technical skills of trainees versus specialists apart from bypass time (less for specialists) and intensive care unit (ICU) length of stay (less for trainees). Studies reporting outcomes on valve surgery also did not report any statistically significant differences amongst the outcomes. CONCLUSION: This systematic review did not discern any significant differences between the procedural outcomes of trainees and specialists, which indicates that trainees are safe to operate under senior supervision. In addition, this article recommends that various procedural outcomes can be used to evaluate the performance of clinicians and healthcare systems. Prospective studies need to be performed, taking into account the specific contribution of trainees and specialists during the procedure. This will give a clearer indication of safety and performance of trainees and specialists in the operating theatre.

Parentage verification in field progeny testing program of Mehsana buffalo.

The present study was undertaken to construct a multiplex microsatellite panel for parentage testing in Mehsana buffalo (Bubalus bubalis). The study was based on a total of 212 Mehsana buffalos (100 dams, 100 daughters, and 12 sires). Genomic DNA was extracted from blood and semen samples. A panel of 10 microsatellite markers (CSSM61, ILSTS29, ILSTS17, ILSTS28, CSSM57, CSSM22, ILSTS61, CSSM8, ETH152, and ILSTS11) was amplified in a single multiplex reaction and analyzed by capillary electrophoresis on an automated DNA sequencer. The expected heterozygosity ranged from 0.642 to 0.833 (mean 0.762). The total exclusion probability using 10 microsatellite loci with 1 known parent was 0.993. Seven out of 10 microsatellite loci revealed relatively high polymorphic information content (>0.7). Eighty-one daughters out of 100 daughters qualified by compatibility according to Mendelism. The results suggest that multiplex microsatellite panel is a fast, robust, reliable, and economic tool to verify the parentage as well as to assign the putative sire to daughters under progeny testing with very high accuracy and hence can be used in routine parentage testing.

Acoustic radiation force impulse quantification: repeatability of measurements in selected liver segments and influence of age, body mass index and liver capsule-to-box distance.

OBJECTIVE: To assess the inter- and intra-observer variability of acoustic radiation force impulse (ARFI) quantification in liver segments with influence of age, body mass index (BMI) and liver capsule-to-box (CB) distance. METHODS: 10 healthy volunteers were examined twice, by three experienced operators, separated by a 1-week interval. 10 readings were obtained, from segments 3, 5/6 and 7/8. Age, BMI and the CB distance were noted. The Cronbach α statistic for analysis of reliability was performed for the inter- and intra-observer studies. Multivariate linear regression models determined significance of the other parameters. RESULTS: 1800 velocity measurements were recorded. Mean values±standard deviation: segment 3, 1.31±0.19 m s(-1); segment 5/6, 1.12±0.22 m s(-1); segment 7/8, 1.12±0.17 m s(-1). For both the inter- and intra-observer study, the Cronbach α statistic was ≥0.7 (reliable) when taken from segments 5/6 and 7/8 but <0.7 (unreliable) for segment 3. BMI and age showed significant (p<0.0001) but contrasting correlation (segment 5/6: BMI r=0.02, age r=-0.02; segment 7/8: BMI r=-0.01, age r=0.01) with ARFI velocities when analysed for the segments deemed reliable. A weak negative correlation between ARFI velocities and liver CB distance was demonstrated for both assessed segments (segment 5/6, r=-0.08; segment 7/8, r=-0.06; p<0.001). CONCLUSION: With trained operators, ARFI is a reliable and reproducible method of liver stiffness quantification in segments 5/6 and 7/8 but acquisition of measurements from segment 3 should be avoided. Values obtained deeper to the liver capsule allow more reliable liver stiffness quantification.

An unusual presentation of late oesophagojejunal anastomotic leak after total D2 gastrectomy.

Oesophagojejunal anastomotic leak usually presents in the early post-operative period with abdominal pain and sepsis. We report a case of late anastomotic leak presenting as epigastric pain with hyperamylasaemia and discuss the differential diagnosis.

Nasopharyngeal chondrolipoma.

In this case report, we describe the presentation and treatment of a patient with nasopharyngeal chondrolipoma. Lipomas are common soft tissue tumours, although their incidence in the nasopharynx is very low. A rarer variant of lipoma, chondrolipomas are benign mesenchymal tumours. They are formed by the proliferation of mature adipocytes and contain different amounts of mature cartilaginous tissue; Weiss "Enzinger and Weiss's soft tissue tumours", 4th ed: Mosby, St Louis; 2001 This represents the second reported case of a nasopharyngeal chondrolipoma. An endonasal approach to excision has not been previously described.

Physicochemical characterization and evaluation of buccal adhesive patches containing propranolol hydrochloride.

Buccal adhesive patches containing 20 mg of propranolol hydrochloride were prepared using solvent casting method. Chitosan was used as a natural bioadhesive polymer. Patches were prepared at different ratios of PVP K-30 and evaluated for various physicochemical characteristics such as weight variation, drug content uniformity, folding endurance, surface pH, ex-vivo mucoadhesive strength, ex-vivo residence time, in vitro drug release and in vitro buccal permeation study. Patches exhibited sustained release over a period of 7 hours. The mechanism of drug release was found to be Non-Fickian diffusion. Addition of PVP K-30 generally enhanced the releasing rate. The ex-vivo mucoadhesive strength was performed using sheep buccal mucosa on modified physical balance. Optimized patches (batch F4) showed satisfactory bioadhesive strength (9.6 degrees 2.0 gram) and ex vivo residence time (272 degrees 0.25 minutes). Swelling index was proportional to PVP K-30. The surface pH of all batches was within satisfactory limit (7.0+/-1.5) and hence patches would not cause irritation in the buccal cavity. Good correlation was observed between in vitro drug release and in vitro drug permeation with correlation coefficient of 0.9364. Stability of optimized patches was performed in natural human saliva showed that both drug and dosage forms were stable in human saliva.

A wandering fish bone.

A unique case is described of an ingested fish bone migrating into the common hepatic duct, without perforation. Most foreign bodies are known to pass through the gastrointestinal tract uneventfully. Sharper objects such as fish bones have been known to cause perforation. This is more common, in countries where fish consumption is considerably higher, such as, south east Asia. However, even in these regions there have been no reports of such a proximal migration.

Validation of image analysis for enzyme histochemical and immunocytochemical staining.

Immunocytochemical and enzyme histochemical analyses of cells and tissues are used to detect changes in the extent of injury and the expression of various molecules. Image analysis quantitation offers an easier, more efficient technique to evaluate these changes. We studied the application of image analysis for evaluating enzyme histochemistry and immunocytochemistry of cells and tissues as a way to assess stroke. Using brain sections, we compared investigator and computer-generated image analysis of 2,3,5-triphenyltetrazolium chloride stained cerebral infarcts in rats subjected to 2 h middle cerebral artery occlusion and 22 h re-perfusion. Both methods documented the infarct volumes with a comparison of means of less then 5%. This suggests no difference between computer- and hand-calculated values. Computer-generated analysis was easier and faster to use. Using endothelial cell monolayers, immunocytochemical staining of a time course of heat shock protein expression was compared to a grading system using fast red chromagen counterstained with hematoxylin. Results demonstrated greater ease and efficiency with computer-generated image analysis compared to other subjective systems of analysis. Image analysis is more useful for detecting small differences in staining, especially when using 3,3-diaminobenzidine as a chromagen. Investigator bias is also reduced using this system. Our comparisons validate the use of this versatile technology to assess more easily both cell and tissues in stroke research.

Non-A, non-B fulminant hepatitis is also non-E and non-C.

OBJECTIVES: to define the roles of the hepatitis C and E viruses (HCV and HEV) in non-A, non-B (NANB) fulminant hepatitis. METHODS: we utilized the polymerase chain reaction to amplify HCV and HEV RNA sequences and assays to detect antibodies to HCV and HEV in the acute phase sera of eight presumed viral NANB and seven nonviral NANB fulminant hepatic failure (FHF) patients. RESULTS: none of the 15 patients had detectable HCV or HEV RNA or elevated HCV and IgM-HEV antibody titers in their acute phase sera. Three patients, all with features of autoimmune hepatitis, had raised IgG-HEV antibody titers. Due to the possibility of serologically undetectable hepatitis B virus (HBV) infection in fulminant hepatitis patients, we performed polymerase chain reaction amplification of HBV genomic DNA in acute phase sera of the presumed viral NANB FHF patients and subsequently found no evidence of HBV DNA. CONCLUSIONS: we did not find evidence implicating HCV or HEV in presumed viral NANB FHF or as agents contributing to or causing the liver failure in nonviral NANB FHF patients with autoimmune hepatitis, drug-induced hepatotoxicity, or halothane hepatotoxicity.

Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas.

Loss of heterozygosity (LOH) at specific loci may help localize tumor suppressor genes involved in the formation of various familial and sporadic tumors. In addition, the genetic loci for a number of familial tumor syndromes have been mapped by linkage analysis. To explore the possible role of tumor suppressor genes in endocrine tumors, we tested 41 pheochromocytomas (34 sporadic and 7 familial) and 11 medullary thyroid cancers (MTC) (10 sporadic and 1 familial) for LOH near a variety of potentially important genetic loci: (a) the multiple endocrine neoplasia type 2A (MEN 2A) locus on chromosome 10; (b) the von Hippel-Lindau locus on 3p; and (c) the p53 and neurofibromatosis 1 loci on 17. We also examined chromosomes 1p and 22q because previous studies in a small number of pheochromocytomas and MTCs suggested LOH in these regions. Background rates for LOH were assessed using several "random" probes. Finally, we examined a number of clinical and histologic characteristics of these tumors for possible correlations with specific genetic alterations. LOH in the region of the MEN 2A locus was uncommon (0% for MTCs, 5% for pheochromocytomas). However, we found significant allelic losses in pheochromocytomas on chromosomes 1p (42%), 3p (16%), 17p (24%), and 22q (31%). We also noted a correlation between LOH on 1p and urinary excretion of metanephrine by these patients (P = 0.02). LOH on 1p, 3p, and 17p also appeared to be associated with increased tumor volume. Analysis of the smaller number of MTCs demonstrated allelic losses on chromosomes 1p and 22q. Our results suggest that tumor formation and/or progression in pheochromocytomas and MTCs involves multiple genes, analogous with the model proposed for colon carcinoma.

Hypothermic-induced electrocerebral silence, prolonged circulatory arrest, and cerebral protection during cardiovascular surgery.

Certain cardiovascular operations require cardiopulmonary bypass and prolonged circulatory arrest to provide an adequate operative field. Profound hypothermia is induced to protect brain function during these periods without cerebral perfusion. Because peripheral body temperatures may not be valid indicators of brain temperature, we conducted this study to establish an alternative, more reliable, method of determining the appropriate level of hypothermia. We measured peripheral body temperatures from 3 sites (rectum, nasopharynx, and esophagus) at the onset of hypothermic-induced electrocerebral silence (ECS) in the intraoperative electroencephalogram (EEG) of 56 adults undergoing cardiovascular procedures. The EEG in most patients showed a characteristic progression of changes from its normal resting state during cooling. Gradual depression and slowing of background rhythms was followed by generalized, periodic, slow-wave transients, prolongation of the intervals between the transients, and then the onset of ECS. In cases in which the slow-wave transients did not appear, the initial depression and slowing of background activity gradually progressed to ECS. No consistent relationship was found between peripheral body temperatures at various sites and the onset of ECS. Using EEG-guided hypothermia, there was low morbidity and mortality. These data suggest that ECS is a safe and reliable guide for determining the appropriate level of hypothermia during cardiovascular procedures.

Determination of brain temperatures for safe circulatory arrest during cardiovascular operation.

Profound hypothermia protects cerebral function during circulatory arrest in the surgical treatment of a variety of cardiac and aortic abnormalities. Despite its importance, techniques to determine the appropriate level of hypothermia vary; studies of temperatures recorded from multiple peripheral body sites show inconsistent findings. The purpose of this study is to establish objective criteria to consistently identify intraoperatively the safe level of hypothermia. Our studies are based on experimental evidence showing a correlation between brain temperature and development of electrocerebral silence (ECS) on the electroencephalogram (EEG), and the recognition that the EEG, as an objective measure of brain function, can easily be recorded intraoperatively. We studied 56 patients who required circulatory arrest during operation for replacement of the ascending aorta or aortic arch (N = 55) or aortic valve replacement (N = 1). Peripheral body temperatures from the nasopharynx, esophagus, and rectum and the EEG were continuously recorded during body cooling. Circulatory arrest time ranged from 14 to 109 minutes. No peripheral body temperature from a single site or from a combination of sites consistently predicted ECS. There was a wide variation in temperature among body sites when ECS occurred: nasopharyngeal, 10.1 degrees to 24.1 degrees C; esophageal, 7.2 degrees to 23.1 degrees C; rectal, 12.8 degrees to 28.6 degrees C. Fifty-one (91%) of the 56 patients survived. Three had neurological deficits, none clearly related to hypothermia. Two patients (3.6%) required reexploration for postoperative bleeding. We conclude that monitoring the EEG to identify ECS is a safe, consistent, and objective method of determining the appropriate level of hypothermia.

The impact of distal aortic perfusion and somatosensory evoked potential monitoring on prevention of paraplegia after aortic aneurysm operation.

Temporary distal aortic perfusion and somatosensory evoked potential monitoring were attempted prospectively in 198 patients to prevent neurologic complications from occurring after operation for descending thoracic and thoracoabdominal aortic aneurysm. These 198 patients were divided into two groups. Group 1 consisted of 99 (50%) patients in whom adequate (60 mm Hg) distal bypass was achieved and combined with somatosensory evoked potential monitoring. Group 2 consisted of 99 (50%) in whom this could not be achieved. Of the latter, four patients were excluded because of operative death in one and preexisting neurologic deficits in three. The rates of early and delayed neurologic complications were 8% and 12%, respectively, in the former and 7% and 8%, respectively, in the latter. Using the logistic regression method of statistical analysis, adjusting for the difference in patient mix, we found no statistical difference in the incidence of neurologic complications in the two groups. The incidence of false negative somatosensory evoked potential response was 13% and false positive response 67%. Localization of critical spinal arteries for reattachment was not possible. Thus, the method had no significant impact upon the prevention of neurologic deficits, which varied from mild or transient to severe and which either occurred during the operation or were delayed from 12 hours to 21 days.

How hyperventilation alters the electroencephalogram: a review of controversial viewpoints emphasizing neurophysiological mechanisms.

This paper reviews the literature on the EEG effects of hyperventilation, with particular emphasis on the literature concerning the mechanism of EEG slowing with hyperventilation. We suggest that there is no definite evidence to support the theory that the EEG slowing and "activation" are caused by hypoxia secondary to cerebral vasoconstriction induced by hypocapnia during voluntary hyperventilation. Since it is known that hypocapnia produces decreased activity in the mesencephalic reticular formation and that lesions of the thalamus abolish the hyperventilation response, we propose a strong, albeit speculative, analogy between awake-sleep transitory states and the mechanism of EEG "activation" by hyperventilation. Furthermore, it is proposed that both the EEG changes and the associated clinical symptomatology (as well as changes in level of anesthesia, which vary with arterial PCO2) may be explained by altered arousal, and that the vasoconstriction observed during hyperventilation is a central neurogenic response to hypocapnia at a brainstem level.

Family planning in Gujarat (1974-75).

PIP: Targets for family planning were exceeded in the Gujarat State of India in 1974-1975. The Gujarat experience is reviewed with the hope that others may use it as an example. Factors in the family planning recruitment success were: 1) advance planning taking local factors into account; 2) use of high financial incentives, with the money raised mostly through private sources; 3) recognition of effective recruiters; 4) use of various types of family planning camps; 5) support by local governments and voluntary organizations; 6) intensification of the pregnancy termination program; 7) combination of child innoculation prog rams with family planning services; 8) operational plans based on field experience; and 9) the interest and support of government officials.^ieng