Athletic groin pain: a systematic review and meta-analysis of surgical versus physical therapy rehabilitation outcomes.

BACKGROUND: Athletic groin pain (AGP) is an encompassing term for the multitude of chronic conditions presenting as pain in the inguinal region. The purpose of this review was to compare the return to play rates (RTPrate) and return to play times (RTPtime) between surgical and rehabilitation interventions in the treatment of AGP. METHODS: A systematic review of English language peer review journals was carried out between 1980 to June 2013 using PubMed, Embase, CINHAL and Google Scholar searching for all papers relating to AGP (and its various pseudonyms) and all surgical and rehabilitative interventions which reported RTPrate and/or RTPtime. AGP literature has been subdivided by many eponymous diagnoses but anatomical diagnostic groupings of (1) abdominal wall, (2) adductor and (3) pubic related pain were used in this review. Meta-analysis was then carried out on the data to compare results between the surgical and rehabilitation groups. RESULTS: Fifty-six papers out of the 561 discovered in the initial search were included in the review with 3332 athletes included. Evidence was mostly level IV. Using the Black and Downs checklist we found poor study quality overall with a high risk of bias especially among surgical studies. The results showed comparable RTPrate between surgical and rehabilitative interventions within the three diagnostic groups. Rehabilitation had significantly quicker RTPtime for pubic related groin pain compared to surgery (10.5 weeks and 23.1 weeks respectively). The abdominal group had the fastest return of the three groups for the rehabilitation and surgery. CONCLUSIONS: The review suggested better outcomes with rehabilitation for pubic-related groin pain with no difference between the adductor and abdominal groups. The review highlighted the poor quality and risk of bias in the literature making accurate comparison difficult.

Evaluating the Ability to ID (COVID-19) NOW: a Large Real-World Prospective Evaluation of the Abbott ID NOW COVID-19 Assay.

The Abbott ID NOW COVID-19 assay is a rapid point-of-care molecular test for SARS-CoV-2 detection. In theory, it has the potential to decrease turnaround times (TATs) and rapidly facilitate patient flow and triage. Reports for its performance have been mixed, likely due to variations in patient cohorts, preanalytical considerations, and study design. We prospectively evaluated the ID NOW performance against reference reverse transcriptase PCR (RT-PCR) tests, using dual swabs. Patients presented at a large multisite academic hospital with the highest volumes of COVID-19 admissions in Canada. From 1,968 valid swabs, 186 were true positive, 1,760 were true negative, 21 were false negatives, and 1 was false positive. At 10.5% positivity rate, the positive and negative predictive values were 99.5% and 98.8%, respectively. This led to a modest increase in the pretest probability in this cohort of individuals presenting <7 days of symptom onset. The mean times from collection to laboratory receipt and receipt to reporting were 31 and 23 min, respectively. This reduced TAT observed in our study may assist with triage of admitted patients and breaking the chain of transmission through immediate notification of status. We also observed how test performance changed with prevalence, and thus, how the test is used to "rule in" or "rule out" disease must be considered. Although the ID NOW is regarded as a rapid test, it is not high throughput and requires rapid transportation times (<1 h) that may not be plausible in large centers. The utility of this test should be considered with the observed TAT and interpreted in the context of limitations discussed. IMPORTANCE Rapid testing for COVID-19 has been recognized as one potentially important measure in managing the pandemic. However, these rapid tests vary grossly in their performance and their applicability. There have been many studies evaluating the performance of rapid tests for SARS-CoV-2 detection. However, they are frequently not prospective, and patients are not simultaneously swabbed to compare the reference standard RT-PCR. Previous ID NOW study findings are mixed, which may be due to various factors, including patient, epidemiological, and preanalytical considerations. It is critical to consider how the pretest and posttest probabilities and epidemiological factors may affect the performance as the community prevalence of disease fluctuates during this highly dynamic pandemic. We consider how the ID NOW may be utilized in different settings, with considerations of public health and infection control and prevention risk tolerance.

The role of clinical history in the interpretation of chest radiographs.

OBJECTIVE: This review will appraise the literature pertaining to the influences that clinical history has on the action of assessing the chest radiograph. KEY FINDINGS: There remains conflicting evidence on the impact of clinical history on chest radiography. Some research suggests that clinical history has the potential to influence the reporter in a negative way by limiting their search strategy to a more focussed search. Image interpretation is more accurate when reporters are allowed to conduct a free search of the chest image, untainted by preconceived concepts. CONCLUSION: Clinical history needs to be accessed appropriately to aid and not stifle accurate image interpretation. Reporters need to be aware of the potential bias clinical history can introduce to their reporting and develop strategies to alleviate this as much as possible. IMPLICATIONS FOR PRACTICE: A greater understanding of the potential bias of clinical history on the process of image interpretation is required by all reporters. Reporters need to develop an approach and strategy when accessing clinical history. Novice reporters need to be educated regarding the impact of clinical history on their reporting.

Bilateral vision loss as the initial presentation for central nervous system involvement of mantle cell lymphoma: A case series.

PURPOSE: Mantle cell lymphoma is a rare aggressive subtype of non-Hodgkins B cell lymphoma. It typically presents with asymptomatic monoclonal lymphocytosis, lymphadenopathy or bulky extranodal disease. Mantle cell lymphoma rarely affects the central nervous system. We present two cases in which vision loss was the initial symptom of central nervous system involvement by the malignancy. OBSERVATIONS: Both patients initially received high dose intravenous steroids with notable improvement in their vision. CONCLUSIONS AND IMPORTANCE: Early detection and management of optic nerve infiltration by mantle cell lymphoma is essential as it improves visual outcomes and enables prompt management of the patient's systemic disease.

Activation of adenylyl cyclase in Chlamydomonas reinhardtii by adhesion and by heat.

Adhesion between Chlamydomonas reinhardtii gametes generates a rapid rise in cAMP levels which stimulates mating responses and zygotic cell fusion (Pasquale and Goodenough, 1987). We show here that sexual adhesion in vivo results in a twofold stimulation of flagellar adenylyl cyclase activity when the enzyme is subsequently assayed in vitro, a stimulation that is specifically blocked by Cd2+. A twofold stimulation is also elicited by the in vitro presentation of soluble cross-linking reagents (antisera and concanavalin A). In contrast, the 10-30-fold stimulation of the flagellar cyclase by in vitro exposure to 40 degrees C, first described by Zhang et al. (1991), is insensitive to Cd2+ but sensitive to such drugs as trifluoperizine and dibucaine. The capacity for twofold stimulation is displayed by the vegetative and gametic enzymes but is lost when gametes fuse to form zygotes; in contrast, the 10-fold stimulation is displayed by the gametic and zygotic enzymes but not the vegetative enzyme. The signal-defective mutant imp-3 fails to generate the normal mating-triggered cAMP production and can be rescued by exogenous dibutyryl cAMP. It displays normal basal rates of flagellar cyclase activity and a normal twofold stimulation by sexual adhesion and by soluble cross-linkers, but it is defective in 40 degrees C activation. The gametic cell-body adenylyl cyclase is stimulated when wild-type flagella, but not imp-3 flagella, undergo adhesive interactions in vivo, and it can be directly stimulated in vitro by cAMP presentation. We propose that the two levels of flagellar cyclase stimulation reflect either sequential steps in the activation of a single cyclase enzyme, with imp-3 blocked in the second step, or else the sequential activation of two different flagellar enzymes, with imp-3 defective in the second enzyme. We further propose that the cell-body enzyme is activated by the cAMP that is generated when flagellar cyclase activity is fully stimulated.

The role of calcium in the Chlamydomonas reinhardtii mating reaction.

The mating reaction of Chlamydomonas reinhardtii entails a rapid series of cell-cell interactions leading to cell fusion. We have demonstrated (Pasquale, S. M., and U. Goodenough. 1987. J. Cell Biol. 105:2279-2293) that cAMP plays a key role in this process: gametic flagellar adhesion elicits a sharp increase in intracellular cAMP, and presentation of dibutyryl-cAMP to unmated gametes elicits all known mating responses. The present study evaluates the role of Ca2+ in this system. We document that the mating-induced increase in cAMP, and hence the mating responses themselves, are blocked by a variety of drugs known to interfere with Ca(2+)-sensitive processes. These data suggest that Ca(2+)-mediated events may couple adhesion to the generation of cAMP. Such events, however, appear to be localized to the flagellar membrane; we find no evidence for the mating-related increase in cytosolic free Ca2+ that has been postulated by others. Indeed, by monitoring the length of the Ca(2+)-sensitive centrin-containing nucleus-basal body connector, we show that cytosolic free Ca2+ levels, if anything, decrease in response to cAMP signaling. We confirm a previous report that Ca2+ levels increase in the mating medium, but document that this represents a response to augmented cAMP levels and not a prelude. Finally, we show that IP3 levels remain constant throughout the mating reaction. These results are discussed in terms of the various signal transduction systems that have now been identified in Chlamydomonas.

Distribution of hepatitis B virus infection in Namibia.

BACKGROUND: Namibia regards hepatitis B virus (HBV) infection as a public health problem and introduced hepatitis B vaccinations for infants during 2009. However, information on HBV infection in the country remains limited, and effective public health interventions may be compromised in the absence of adequate evidence-based data. Available data from the World Health Organization (WHO) estimate that 15 - 60% of the normal population in many African countries may be positive for one or more of the HBV serological markers. OBJECTIVE: To investigate the distribution of HBV infection in Namibia, using available laboratory data for 2013. METHODS: A cross-sectional descriptive study was conducted using pre-existing electronic laboratory data on HBV infection. The data were retrieved from the central Namibia Institute of Pathology laboratory in Windhoek during January - December 2013. Tests were done on the following three main groups: (i) pregnant women during routine antenatal care (ANC) visits; (ii) patients with HIV/AIDS during antiretroviral therapy clinic visits; and (iii) any other individual suspected of having HBV infection. RESULTS: Of a total of 77 238 hepatitis B surface antigen test results retrieved countrywide, 9 087 (11.8%) were positive. Of the positive results, 246/9 087 (2.7%) were in children aged 0 - 14 years, with the sexes equally affected. HBV infections increased markedly, particularly among females, in the age group 15 - 39 years, reaching a peak in the age group 30 - 34 years. Routine screening of pregnant women for HBV during ANC visits was found to be systematically conducted in only two regions, Ohangwena and Khomas. CONCLUSIONS: This study showed high proportions of positive results in pregnant women, patients with HIV/AIDS and individuals suspected of having HBV infection. The Ministry of Health and Social Services and stakeholders may wish to consider improving the routine and surveillance reporting systems for viral hepatitis and uptake of screening for pregnant women in all regions, and expanding HBV screening to other population groups. Population-based or similar studies are therefore required to determine the HBV prevalence and risk factors. This will assist Namibia in developing appropriate national viral hepatitis strategies as per WHO recommendations.

A phase I trial of a human papillomavirus (HPV) peptide vaccine for women with high-grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive.

Eighteen women with high-grade cervical or vulvar intraepithelial neoplasia who were positive for human papillomavirus (HPV) 16 and were HLA-A2 positive were treated with escalating doses of a vaccine consisting of a 9-amino acid peptide from amino acids 12-20 encoded by the E7 gene emulsified with incomplete Freund's adjuvant. Starting with the eleventh patient, an 8-amino acid peptide 86-93 linked to a helper T-cell epitope peptide with a covalently linked lipid tail was added. Patients with colposcopically and biopsy-proven cervical intraepithelial neoplasia/vulvar intraepithelial neoplasia II/III received four immunizations of increasing doses of the vaccine each 3 weeks apart, followed by a repeat colposcopy and definitive removal of dysplastic tissue 3 weeks after the fourth immunization. Patients were skin tested with the E7 12-20 peptide as well as control candida, mumps, and saline prior to and after the series of immunizations. Peripheral blood mononuclear cells were obtained by leucopheresis prior to and after the series of immunizations for analyses of CTL reactivity to the E7 12-20 and 86-93 epitope sequences. The presence of HPV 16 was assessed by DNA PCR on cervical scrapings and the biopsy specimens after vaccination. Pathology specimens were analyzed before and after vaccination for the presence of dysplasia, and the intralesional infiltrate of CD4/CD8 T-cells and dendritic cells was measured by immunohistochemical staining. Only 3 of 18 patients cleared their dysplasia after vaccine, but an increased S100+ dendritic cell infiltrate was observed in 6 of 6 patients tested. Cytokine release and cytolysis assays to measure E7-specific reactivity revealed increases in 10 of 16 patients tested. No positive delayed type hypersensitivity skin test reactivity was shown in any patient to HPV E7 12-20 before or after vaccinations. Virological assays showed that 12 of 18 patients cleared the virus from cervical scrapings by the fourth vaccine injection, but all biopsy samples were still positive by in situ RNA hybridization after vaccination. Six patients had partial colposcopically measured regression of their cervical intraepithelial neoplastic lesions in addition to the three complete responders. The data establish that a HPV-16 peptide vaccine may have important biological and clinical effects and suggest that future refinements of an HPV vaccine strategy to boost antigen-specific immunity should be explored.

A murine model for the effects of pelvic radiation and cisplatin chemotherapy on human papillomavirus vaccine efficacy.

Therapeutic human papillomavirus (HPV) vaccines for cervical cancer depend on a competent immune system to be effective. However, cancer patients are often found to be immunosuppressed, which could be attributable to prior radiation, chemotherapy, or the tumor burden itself. This study investigated whether pelvic radiation or cisplatin treatment affected the efficacy of an HPV vaccine and how long these effects lasted. Mice were given pelvic radiation, 2 Gy/day to a total dose of 45 Gy, or 5 mg/kg/week of cisplatin for 3 weeks. Mice were then immunized with an HPV-16 peptide vaccine between 0 and 16 weeks after their treatment. An ELISPOT analysis revealed that a reduced level of peptide-specific, IFNgamma-producing spleen cells was present in immunized mice treated previously with pelvic radiation or cisplatin compared with immunized mice that had not been treated. However, when mice were challenged with HPV-16-expressing tumor cells, immunized mice developed no tumors, regardless of prior treatment, whereas nonimmunized mice did develop tumors. Our results suggest that pretreatment with pelvic radiation or cisplatin alone does not prevent the induction of an effective immune response by a peptide vaccine. These data will have important implications for immunotherapeutic treatment of pretreated cancer patients, especially in the adjuvant setting when immunosuppression by tumor burden would be low.

Partial synthesis of 6'-hydroxycinchonine and its antiarrhythmic activity in mice.

The synthesis of 6'-hydroxycinchonine [8R,9S)-cinchonan-6',9-diol] was achieved by demethylating quinidine with boron tribromide in dichloromethane at -75 degrees C. The antiarrhythmic activities of 6'-hydroxycinchonine and quinidine were compared following the infusion of aconitine into the tail veins of mice to induce arrhythmias. Comparative ED50 and LD50 studies for quinidine and 6'-hydroxycinchonine revealed equivalent antiarrhythmic potencies for the two drugs but a smaller acute toxicity for 6'-hydroxycinchonine.

Assessing exposure to disinfection by-products in women of reproductive age living in Corpus Christi, Texas, and Cobb county, Georgia: descriptive results and methods.

We conducted a field study in Corpus Christi, Texas, and Cobb County, Georgia, to evaluate exposure measures for disinfection by-products, with special emphasis on trihalomethanes (THMs). Participants were mothers living in either geographic area who had given birth to healthy infants from June 1998 through May 1999. We assessed exposure by sampling blood and water and obtaining information about water use habits and tap water characteristics. Two 10-mL whole blood samples were collected from each participant before and immediately after her shower. Levels of individual THM species (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) were measured in whole blood [parts per trillion (pptr)] and in water samples (parts per billion). In the Corpus Christi water samples, brominated compounds accounted for 71% of the total THM concentration by weight; in Cobb County, chloroform accounted for 88%. Significant differences in blood THM levels were observed between study locations. For example, the median baseline blood level of bromoform was 0.3 pptr and 3.5 pptr for participants in Cobb County and Corpus Christi, respectively (p = 0.0001). Differences were most striking in blood obtained after showering. For bromoform, the median blood levels were 0.5 pptr and 17 pptr for participants in Cobb County and Corpus Christi, respectively (p = 0.0001). These results suggest that blood levels of THM species vary substantially across populations, depending on both water quality characteristics and water use activities. Such variation has important implications for epidemiologic studies of the potential health effects of disinfection by-products.

Enzymatic Capability of HIS-Tagged HIV-1 Integrase Using Oligonucleotide Disintegration Substrates.

Disintegration, wherein a half-site integration substrate is resolved into separate viral and host DNA components via DNA strand transfer, is one of three well-established in vitro activities of HIV-1 integrase. The role of disintegration in the HIV-1 replicative cycle, however, remains a mystery. In this report, we describe the expression in Escherichia coli and purification of HIV-1 integrase as a fusion protein containing a 6xHis tag at its amino terminus. Integrase resolved dumbbell and Y-substrates optimally at pH 6.8-7.2 in the presence of 2 mM MnCl(2). Substrate requirements for intramolecular disintegration included a 10 base pair viral U5 LTR arm and a CA dinucleotide located at the 3' end of the LTR. Disintegration was not sensitive to changes in the host DNA portion of the substrate. A dumbbell substrate with a 5' oligo-dA tail also underwent disintegration. The released LTR arm with an oligo-dA tail was utilized as a template primer by several DNA polymerases indicating that disintegration occurred via nucleophilic attack on the phosphodiester bond located immediately adjacent to the CA dinucleotide at the 3' end of the LTR. Coupled disintegration-DNA polymerase reactions provided a highly efficient and sensitive means of detecting disintegration activity. Integrase also catalyzed an apparently concerted disintegration-5'-end joining reaction in which an LTR arm was transferred from one dumbbell substrate molecule to another. Copyright 1996 S. Karger AG, Basel

The origin and composition of peroxidase-positive granules in cysteamine-treated astrocytes in culture.

Gomori astrocytes, which are prominent in periventricular regions of the brain, contain inclusions that stain with Gomori dyes, and exhibit an orange-red autofluorescence and a non-enzymatic peroxidase activity. Recently, such astrocytes have been induced in dispersed glial cultures by exposure to cysteamine. Using these cells, we have shown that the peroxidase-positive inclusions (Gomori bodies) are multicompartmental, that iron co-localizes with the peroxidase activity, and that the iron is often segregated in one of the compartments of the body. The goal of the present study was to determine the origin and process of formation of these bodies. The results indicate that cysteamine induces aberrations in mitochondrial structure associated with the acquisition of iron and the associated peroxidase activity. Mitochondria thus transformed appear to initiate an autophagic process in which they, and adjacent structures, are sequestered. The presence of acid phosphatase activity in a number of mature Gomori bodies attests to the participation of lysosomal elements in this process. These results indicate, therefore, that the Gomori body is a complex autophagosome in which the iron-containing compartments, putatively responsible for the peroxidase activity, represent undegraded transformed mitochondria.

A comparative study on the antiarrhythmic activity and acute toxicity of quinidine and four new analogs in mice.

We have compared the ED50 value for antiarrhythmic activity and the acute toxicities in mice of quinidine and 4 recently synthesized analogs. For the ED50 studies, groups of mice were treated intravenously with equally spaced logarithmic doses of 6'-methoxycinchonine (quinidine), 6'-hydroxycinchonine (cupreidine), 6'-isovaleryloxycinchonine, 6'-acetyloxycinchonine and 6'-benzoyloxycinchonine. For the actue toxicity studies, mice were treated intraperitoneally with quinidine and the 4 analogs. Mice were observed over a 24-h period, and thereafter for each additional 24-h period for a total of 120 h. Tests for parallelism of acute toxicity indicated that with the exception of the 6'-isovaleryloxy derivative the drug treatment regression lines were parallel to that of quinidine (P > 0.05). The results indicated decreases of 50% (843 mumol/kg), 52% (857 mumol/kg), and 61% (910 mumol/kg) in the acute toxicities of the 6'-acetyloxy, 6'-hydroxy, and 6'-benzoyloxycinchonine, respectively. The 6'-acetyloxy (18.5 mumol/kg) and 6'-benzoyloxy (14.6 mumol/kg) derivatives had significantly lower ED50 values than quinidine (60.1 mumol/kg). The results suggest that the 6'-acetyloxy and 6'-benzoyloxy derivatives may have much greater antiarrhythmic effectiveness than quinidine.

Uptake and subcellular distribution of 51Cr in Gomori-positive astrocytes in primary culture.

An unusual population of astrocytes containing Gomori-positive inclusions occurs in periventricular regions of the brain in all mammalian species. The inclusions are autofluorescent and exhibit non-enzymatic peroxidase activity. Estradiol treatment in vivo and cysteamine treatment in vitro have been shown to increase the number and size of these inclusions. Recent studies indicate that the Gomori inclusions are accumulations of autophagocytized abnormal mitochondria. The mitochondrial changes initiating Gomori inclusion formation begin with a loss of cristae. Energy dispersive X-ray microanalysis also reveals small emission peaks indicative of chromium. The appearance of chromium peaks in the initial stages of mitochondrial transformation suggests that enhanced permeability to chromium could play a causal role in generating Gomori inclusions. In the present study, we have examined the uptake and intracellular distribution of chromium during Gomori inclusion formation in cysteamine-treated cultured astrocytes. 51Cr was added to the media of glial cultures 24 hours prior to the initiation of the formation of Gomori inclusions by the addition of cysteamine. Cultures were fixed and prepared for EM radioautography at 12, 24, and 72 hours following the addition of cysteamine. 51Cr was added to control cells but they were not treated with cysteamine, and, they did not, therefore, develop Gomori inclusions. Cysteamine exposure resulted in a rapid sustained increase in radiolabel over the astrocytes. Much of the label was concentrated over mitochondria. At the late time points, label concentrated progressively over developing Gomori inclusions. These results confirm that the onset of Gomori inclusion formation coincides with increase cellular permeability to chromium and they indicate that uptake of chromium by mitochondria may play an important role in initiating development of these structures.

Synthesis and preliminary antimicrobial screening of two thiosulfonates.

Tetramethylene bis(methanethiosulfonate), the S-ester analog of busulfan, was prepared by reacting 1,4-dibromobutane with potassium methanethiosulfonate. 2,4-Dichlorophenyl methanethiosulfonate was prepared by reacting sodium methanesulfinate with 2,4-dichlorobenzenesulfenyl chloride. Neither compound showed antifungal activity against Microsporum audouini or Trichophyton mentagrophytes. Although tetramethylene bis(methanethiosulfonate) was more active against Staphylococcus aureus than was 2,4-dichlorophenyl methanethiosulfonate, neither compound was as active as the streptomycin control.

Instrumentation of an automatic capsule-filling machine.

Techniques similar to those used in instrumenting tablet presses were applied to an automatic capsule-filling machine. The dosing unit was modified to allow the bonding of strain gauges to the compression piston. The guages formed the arms of a Wheatstone bridge circuit. Thus, compression and ejection events were monitored by measuring the bridge unbalance voltage using a suitable amplifier-recording system. The instrumented piston was calibrated in a physical testing machine. Dosing unit rotation required the interposing of a mercury contact swivel between the amplifier and instrumented piston. The instrumentation system required only one minor, permanent modification to the machine, a cut in the dosator tube. Since the same dosator piston sensed both compression and ejection, only one of the two dosing units was instrumented and the other was removed from the machine. A solenoid switching system was devised which only permitted the feeding of empty gelatin shells into the filling cycle for the instrumented piston. Representative fillers were run at constant powder bed and piston heights. Oscilloscope tracings showed two stages in slug formation: (a) "precompression," representing the force sensed during dipping of the dosator into the powder before actual compression, and (b) actual piston compression. Generally, the maximum slug compression force fell to zero rapidly on retraction of the piston, but in some cases a retention force was noted, possibly due to elastric rebound of the slug against the retracted piston. A negative deflection due to binding of the piston also was observed in tracings of one material. Lubricated batches exhibited ejection forces of less than 1 kg.

Emergency physicians' duty to warn and protect: a critique and guidelines.

For ten years, psychotherapists in California have practiced under a court decision which imposed a duty to warn intended victims of violent crimes. Other cases extended the scope of the psychotherapists' duty to warn to an alarming degree. Although there have been no court cases involving emergency physicians, it is reasonable to assume that, under certain circumstances, the duty to warn could be extended to primary care physicians. Emergency physicians should familiarize themselves with applicable case law and should be aware of measures to use to avoid potential civil liability.

Electrical stimulation of post-mortem glycolysis in the Semitendinosus muscle of sheep.

Changes in pH and phosphorylase a content in control and electrically stimulated Semitendinosus muscles of sheep were studied. The results provided evidence of acceleration of glycolysis during slaughter and sampling. In muscle electrically stimulated soon after slaughter there was a transient increase in phosphorylase a during stimulation. The magnitude of this increase and of the fall in pH during stimulation both depended on the pH of the muscle at the time of stimulation and reduced to zero when this pH was about 6·3. There was little or no phosphorylase a in samples of muscle taken about 35 min post mortem or, at any time, in muscle electrically stimulated about 35 min post mortem. Possible reasons for the transient nature of the increase in phosphorylase a content during stimulation are discussed.

Quantitative analysis of quinidine analogs using ion-pairing HPLC.

Quinidine, a useful antiarrhythmic compound, is usually contaminated with dihydroquinidine, a compound that itself shows potent antiarrhythmic activity. Complete hydrogenation of quinidine followed by conversion to dihydroquinidine derivatives was explored as a basis for eliminating the analytical problems inherent in the quality control of quinidine products and for determining their pharmacological potency and pharmacokinetic parameters without interfering impurities. Attempts to resolve the quinidine analogs, dihydrocupreidine, and its benzoyloxy ester failed with normal and reversed-phase chromatography. Ion-pairing chromatography using n-octanesulfonate in methanol:water proved successful. Using 9-hydroxy-4-methoxy acridine as internal standard, separation and quantitation of the dihydroquinidine analogs from spiked plasma samples was achieved with 92 to 95% efficiency.