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A C Schmidt

Publications and source records attributed to A C Schmidt.

At least 19 recordsLinked to original sources

Solid-state characterization of non-stoichiometric hydrates of ester-type local anaesthetics. Part XI. Crystal polymorphism of local anaesthetic drugs.

Three structurally closely related local anaesthetic drugs, hydroxyprocaine hydrochloride (4-butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, HPCHC), tetracaine hydrochloride (4-butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, TCHC) and hydroxytetracaine hydrochloride (4-butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, SLCHC) are found to form hydrated crystals. Those were characterized by thermal analysis (hot stage microscopy, differential scanning calorimetry, thermogravimetry), vibrational spectroscopic methods (FTIR-, FT-Raman-spectroscopy), powder X-ray diffractometry, solid-state NMR and water sorption/desorption analysis. The formation and the stability of the hydrated solid phases are evaluated by sorption isotherms derived from different sorption/desorption analytic methods. The three substances investigated show conformational polymorphism with the anhydrated phases including a high temperature form mod. I, which is highly hygroscopic and isostructural with the hydrate. The hydrated form is present in commercial products at various contents. These hemihydrates crystallize from water, whereas the anhydrates crystallize from all other tested organic solvents. Different methods of water sorption/desorption analysis indicate the formation of non-stoichiometric hydrates. Different methods of drying lead to the same results. Solid-state NMR spectra were used to obtain both structural and molecular level mobility information.

Adsorption↗

Polymorphism and pseudopolymorphism of salicaine and salicaine hydrochloride crystal polymorphism of local anaesthetic drugs, part V.

The local anaesthetic drug salicaine hydrochloride (hydroxytetracaine hydrochloride, 4-butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, SLCHC) and the free-base salicaine (SLC) were characterized by thermal analysis, vibrational and solid-state NMR-spectroscopy, X-ray powder diffraction, X-ray single crystal structure analysis, and water vapor sorption analysis. Additionally, the crystal structures of the anhydrate mod. II degrees (monoclinic, space group P2(1)/n), the hydrated mod. I (triclinic, space group P(bar)1), and of the free base (SLC) in the form of the hemihydrate (triclinic, space group P(bar)1 are discussed. Mod. II degrees of the polymorphic SLCHC is the thermodynamically stable form at room temperature and is present in commercial products mostly contaminated with a hydrated form that is isomorphic with mod. I. Mod. II degrees crystallizes from most organic solvents and from the melt below 110 degrees C. Mod. I crystallizes from the melt at temperatures above 110 degrees C, and additionally appears on dehydration of the hydrated mod. I. A third polymorph monotropically related to mod. II degrees was found by freeze-drying. The free-base SLC was found to crystallize from ethanol/water as a triclinic hemihydrate.

Absorption↗

Structural characteristics and crystal polymorphism of three local anaesthetic bases crystal polymorphism of local anaesthetic drugs: part VII.

Benzocaine (BZC), butambene (BTN) and isobutambene (BTI) are basic local anaesthetic agents of the ester type, preferentially used for surgery and dental procedures. The compounds, official in the USP (BZC and BTN) and Ph. Eur. (BZC), were each found to exist in two polymorphic crystal forms and their solid state characteristics have been determined by thermomicroscopy, differential scanning calorimetry (DSC), FTIR-, FT-Raman-spectroscopy as well as X-ray powder diffractometry. This work further emphasizes the comparison of solid state characteristics of three compounds with closely related structural features on molecular level, leading to opportunities for the investigation of structure-property relationships. Mod. I0 is the particular thermodynamically stable form at room temperature in all of the three systems. This form is present in commercial products and can be crystallized from solvents at room conditions. Mod. II can be obtained by annealing the supercooled melt or fast cooling of a saturated solution, respectively. The endothermic transformation of mod. II to mod. I0 upon heating confirms that mod. I0 is thermodynamically stable at ambient conditions (heat of transition rule) whereas mod. II is enantiotropically related to mod. I0, i.e. is metastable at temperatures above the transition temperature. The metastable forms show different kinetic stabilities at room temperature.

Anesthetics, Local↗

Recombinant bovine/human parainfluenza virus type 3 (B/HPIV3) expressing the respiratory syncytial virus (RSV) G and F proteins can be used to achieve simultaneous mucosal immunization against RSV and HPIV3.

Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3 counterparts, was used to express the major protective antigens of respiratory syncytial virus (RSV) in order to create a bivalent mucosal vaccine against RSV and HPIV3. The attenuation of rB/HPIV3 is provided by the host range restriction of the BPIV3 backbone in primates. RSV G and F open reading frames (ORFs) were placed under the control of PIV3 transcription signals and inserted individually into the rB/HPIV3 genome in the promoter-proximal position preceding the nucleocapsid protein gene. The recombinant PIV3 expressing the RSV G ORF (rB/HPIV3-G1) was not restricted in its replication in vitro, whereas the virus expressing the RSV F ORF (rB/HPIV3-F1) was eightfold restricted compared to its rB/HPIV3 parent. Both viruses replicated efficiently in the respiratory tract of hamsters, and each induced RSV serum antibody titers similar to those induced by RSV infection and anti-HPIV3 titers similar to those induced by HPIV3 infection. Immunization of hamsters with rB/HPIV3-G1, rB/HPIV3-F1, or a combination of both viruses resulted in a high level of resistance to challenge with RSV or HPIV3 28 days later. These results describe a vaccine strategy that obviates the technical challenges associated with a live attenuated RSV vaccine, providing, against the two leading viral agents of pediatric respiratory tract disease, a bivalent vaccine whose attenuation phenotype is based on the extensive host range sequence differences of BPIV3.

Animals↗

Evaluation of extraction procedures for the ion chromatographic determination of arsenic species in plant materials.

The determination of arsenic species in plants grown on contaminated sediments and soils is important in order to understand the uptake, transfer and accumulation processes of arsenic. For the separation and detection of arsenic species, hyphenated techniques can be applied successfully in many cases. A lack of investigations exists in the handling (e.g., sampling, pre-treatment and extraction) of redox- and chemically labile arsenic species prior to analysis. This paper presents an application of pressurized liquid extraction (PLE) using water as the solvent for the effective extraction of arsenic species from freshly harvested plants. The method was optimized with respect to extraction time, number of extraction steps and temperature. The thermal stability of the inorganic and organic arsenic species under PLE conditions (60-180 degrees C) was tested. The adaptation of the proposed extraction method to freeze-dried, fine-grained material was limited because of the insufficient reproducibility in some cases.

Arsenic↗

Determination of arsenic species in water, soils and plants.

Ion chromatographic separation coupled with ICP-MS was used to determine arsenic species in plant and soil extracts. A scheme for growth, harvesting, sample pre-treatment and analysis was developed for the arsenic species to enable determination. Preliminary results obtained with ten herb plants grown on arsenic-contaminated soil compared to non-contaminated soil show a heterogeneous pattern of accumulation rate, metabolization and detoxification mechanisms in monocots and dicots. Arsenite appears to be the major component in plants with good growth. Organic arsenic species were even detected at very low concentrations (< 150 microg kg(-1) (dry mass)).

Arsenic↗

Bovine parainfluenza virus type 3 (BPIV3) fusion and hemagglutinin-neuraminidase glycoproteins make an important contribution to the restricted replication of BPIV3 in primates.

This study examines the contribution of the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein genes of bovine parainfluenza virus type 3 (BPIV3) to its restricted replication in the respiratory tract of nonhuman primates. A chimeric recombinant human parainfluenza type 3 virus (HPIV3) containing BPIV3 F and HN glycoprotein genes in place of its own and the reciprocal recombinant consisting of BPIV3 bearing the HPIV3 F and HN genes (rBPIV3-F(H)HN(H)) were generated to assess the effect of glycoprotein substitution on replication of HPIV3 and BPIV3 in the upper and lower respiratory tract of rhesus monkeys. The chimeric viruses were readily recovered and replicated in simian LLC-MK2 cells to a level comparable to that of their parental viruses, suggesting that the heterologous glycoproteins were compatible with the PIV3 internal proteins. HPIV3 bearing the BPIV3 F and HN genes was restricted in replication in rhesus monkeys to a level similar to that of its BPIV3 parent virus, indicating that the glycoprotein genes of BPIV3 are major determinants of its host range restriction of replication in rhesus monkeys. rBPIV3-F(H)HN(H) replicated in rhesus monkeys to a level intermediate between that of HPIV3 and BPIV3. This observation indicates that the F and HN genes make a significant contribution to the overall attenuation of BPIV3 for rhesus monkeys. Furthermore, it shows that BPIV3 sequences outside the F and HN region also contribute to the attenuation phenotype in primates, a finding consistent with the previous demonstration that the nucleoprotein coding sequence of BPIV3 is a determinant of its attenuation for primates. Despite its restricted replication in the respiratory tract of rhesus monkeys, rBPIV3-F(H)HN(H) conferred a level of protection against challenge with HPIV3 that was indistinguishable from that induced by previous infection with wild-type HPIV3. The usefulness of rBPIV3-F(H)HN(H) as a vaccine candidate against HPIV3 and as a vector for other viral antigens is discussed.

Animals↗

Oklahoma Firearm-Related Injury Surveillance.

CONTEXT: The magnitude of firearm-related deaths is known, but few studies have evaluated the magnitude and epidemiology of nonfatal firearm-related injuries. The circumstances resulting in fatal versus nonfatal injury are likely very different. No single data source provides complete details on nonfatal shootings. OBJECTIVE: To establish a surveillance system to define the epidemiology of fatal and nonfatal firearm-related injuries. DESIGN: Data were collected on fatal and nonfatal firearm-related injuries that occurred in 1995. SETTING: State of Oklahoma. PARTICIPANTS: Medical Examiner, Vital Statistics, hospital emergency and medical records departments, police departments, newspaper clipping service. MAIN OUTCOME MEASURES: Incidence rate of firearm-related injuries; case-fatality rate; demographic, medical, and epidemiologic data; sensitivity of each reporting source; completeness of reporting. RESULTS: The incidence rate of firearm-related injuries was 45.5 per 100,000 population. The case fatality rate was 35%. Injury rates were highest among adolescents, young adults, males, and African Americans. The Medical Examiner and Vital Statistics reported 87% and 98% of fatal cases, respectively. Passive surveillance of hospital emergency departments identified 72% of patients seeking hospital treatment. Among inpatients, 81% were identified by medical records departments. Newspaper clippings were obtained for 31% of cases. Information on the victim-perpetrator relationship and the type of firearm was available for 79% and 80% of cases, respectively. CONCLUSIONS: Statewide surveillance of firearm-related injuries using multiple data sources is possible and provides a picture of the overall firearm-related injury problem. Strategies to enhance computer linkages of medical and police data should be pursued to maximize the sensitivity of reporting and minimize the costs of surveillance.

Adolescent↗

Assignment of disulfide bridges in the fusion glycoprotein of Sendai virus.

The mature fusion (F) glycoprotein of the paramyxovirus family consists of two disulfide-linked subunits, the N-terminal F2 and the C-terminal F1 subunits, and contains 10 cysteine residues which are highly conserved at specific positions. The high level of conservation strongly suggests that they are indeed disulfide linked and play important roles in the folding and functioning of the molecule. However, it has not even been clarified which cysteine residues link the F2 and F1 subunits. This report describes our assignment of the disulfide bridges in purified Sendai virus F glycoprotein by fragmentation of the polypeptide and isolation of cystine-containing peptides and determination of their N-terminal sequences. The data demonstrate that all of the 10 cysteine residues participate in disulfide bridges and that Cys-70, the only cysteine in F2, and Cys-199, the most upstream cysteine in F1, form the interchain bond. Of the remaining eight cysteine residues clustered near the transmembrane domain of F1, the specific bridges identified are Cys-338 to Cys-347 and Cys-362 to Cys-370. Although no exact pairings between the subsequent four residues were defined, it seems likely that the most downstream, Cys-424, is linked to Cys-394, Cys-399, or Cys-401. Thus, we conclude that the cysteine-rich domain indeed contributes to the formation of a bunched structure containing at least two tandem cystine loops.

Amino Acid Sequence↗

Peripheral blood lymphocyte response in patients with superficial transitional cell carcinoma of the bladder treated with intravesical Bacillus Calmette-Guérin--a useful marker of response?

Intravesical instillation of Bacillus Calmette-Guérin (BCG) offers safe and effective short-term/long-term treatment for superficial transitional cell carcinoma (TCC) and TCC in situ of the bladder. However, 17 to 42% of patients may experience recurrence in spite of this therapy and a marker of effective treatment is of paramount importance. In this study the in vitro response of peripheral blood lymphocytes (PBL) to BCG was analysed in 10 patients with superficial TCC and TCC in situ before and during BCG instillations. The in vitro response of PBL to BCG, expressed as a stimulatory index (SI), revealed that 6 patients had a SI > 5 and 4 patients had a SI < 5. None of the former patients had recurrence of TCC during a mean follow-up of 17 months, while all of the latter patients experienced recurrence of TCC within 9 months. It was concluded that the in vitro response of PBL to BCG may be used as a marker of response to intravesical BCG treatment.

Adult↗

[Intravesical BCG as a treatment for superficial and in situ transitional cell carcinoma of the bladder].

Intravesical BCG is already established as effective therapy in the management of superficial bladder cancer. However, varying results have been obtained with different BCG strains; these are ascribed to variations in their immunogenicity. The locally available BCG strain which contains approximately 1.2 x 10(9) colony-forming units per 120 mg was used for intravesical instillation in 27 patients with recurrent superficial transitional cancer of the bladder. Ten of the 13 patients who received BCG prophylactically to reduce or stop recurrencies completed therapy and 7 (70%) were in remission after 1 or 2 courses with a mean follow-up of 2 years. Fourteen patients received BCG therapeutically for in situ carcinoma. Thirteen of these patients completed therapy and 9 (69%) responded favourably after 1 or 2 courses of BCG for a mean follow-up period of 23 months. Adverse effects of the treatment were mild and well tolerated except in a patient who received radiotherapy. Although 21 patients experienced irritable bladder symptoms only 1 discontinued treatment as a direct result. The only other patient in whom treatment had to be stopped, developed severe polyarthritis after 3 instillations. A statistically significant reduction in the number of recurrences (P less than 0.001) was experienced by the patients who received BCG prophylactically. Although this is a very limited study, the locally available BCG strain exhibited therapeutic activity. It is cost-effective and warrants further study.

Administration, Topical↗

Percutaneous nephrolithotomy. Experience with renal and proximal ureteral calculi at Tygerberg Hospital.

Percutaneous nephrolithotomy (PCN) enables the urologist to remove upper urinary tract stones through a percutaneous nephrostomy tract. The principal advantages of PCN are the low morbidity, shortened hospital stay and rapid recovery. Percutaneous puncture failed in 5 (11%) of the first 44 patients with upper tract urolithiasis treated by PCN at Tygerberg Hospital. In 35 patients (80%) PCN cleared the kidney of stones but in 4 patients (9%) all stone fragments were not removed during the procedure. If the puncture and dilatation was successful, then 90% of patients were stone-free after PCN. Complications were minimal except for a diabetic who died of septicaemia. PCN is an alternative to open renal surgery in the management of most upper urinary tract stones. The technique is readily mastered by any urologist experienced in endoscopic surgery.

Adolescent↗