Pharmacologic management of postdural puncture headache.

OBJECTIVE: To discuss the pathogenesis, incidence, and clinical presentation of postdural puncture headaches (PDPHs) and to provide a comprehensive evaluation on the pharmacologic management of PDPH. DATA SOURCE: A MEDLINE search was used to identify pertinent literature published in English including review articles, case reports, letters, and abstracts. Information was also extracted from textbooks for background purposes. STUDY SELECTION: All clinical studies, case reports, abstracts, and letters were included because of the limited amount of literature available on the pharmacologic therapy for PDPH. Related research articles and review articles were also used to provide background information on PDPH. DATA EXTRACTION: Methodology and results from clinical trials and abstracts were described and evaluated. Case reports and letters were summarized and critically reviewed for the feasibility of the different treatment modalities. Information on the pathophysiology, incidence and severity, and clinical presentation of PDPH was extracted from related research articles, review articles, and textbooks. DATA SYNTHESIS: The epidural blood patch (EBP) is one of the most effective treatments for PDPH. Pharmacologic management of PDPH offers a less invasive treatment modality than the EBP. Numerous drug therapies have been presented in the literature, though few merit clinical application. Caffeine therapy, both oral and parenteral, is the most commonly used pharmacologic treatment modality. Theophylline and sumatriptan are potentially promising agents for the treatment of PDPH. Epidural administration of fluids and drugs is also effective in the treatment of PDPH. Epidural adrenocorticotropic hormone and epidural morphine also demonstrate some potential in the treatment of PDPH. Individual patient characteristics (i.e., HIV, sepsis) need to be considered when deciding on a treatment. More reports, especially clinical studies, are necessary before a definitive statement can be made regarding any one treatment. In the meantime, therapy will be guided by clinical judgement based on the literature reviewed in this article. CONCLUSIONS: Intravenous and oral caffeine are effective and noninvasive treatments for PDPH. Epidural NaCl 0.9% or dextran are alternatives when the EBP is unsuccessful or contraindicated. Several methods of pharmacologic management have been cited in the literature, but all require further evaluation.

Pharmacokinetics of intravaginal metronidazole gel.

The pharmacokinetics of a single 500 mg oral dose of metronidazole and 5 g of 0.75% metronidazole intravaginal gel (37.5 mg metronidazole) were compared in 12 adult volunteers in a randomized crossover manner. Serial serum samples were collected over a 48-hour period and analyzed for metronidazole and hydroxymetronidazole. Metronidazole serum concentrations after intravaginal administration were only 2% of concentrations seen with the standard 500-mg oral dose. The dose-adjusted maximum serum concentration (898 +/- 121 ng/mL vs. 237 +/- 69 ng/mL) and area under the serum concentration-time curve (9362 +/- 2873 ng * hr/mL vs. 4977 +/- 2671 ng * hr/mL) were significantly greater for the oral versus intravaginal dose of metronidazole. The time to reach maximum concentration (1.4 +/- 0.6 hr vs. 8.4 +/- 2.2 hr) was significantly shorter for the oral compared with the intravaginal dose. The mean bioavailability for the intravaginal gel was 56%. Our results show that the 0.75% gel formulation may offer the advantage of fewer systemic adverse effects compared with other formulations for the treatment of bacterial vaginosis.

Comparative pharmacokinetics of oral versus sublingual clonidine.

STUDY OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic profile of orally versus sublingually administered clonidine. DESIGN: Randomized, crossover, nonblinded, open-label study. SETTING: University tertiary-care center. PATIENTS: 10 healthy male and female volunteers aged 20 to 42 years. INTERVENTIONS: A heparinized catheter was placed intravenously for blood-sampling purposes. An automatic sphygmomanometer was placed on the volunteers' left upper arm to obtain systolic and diastolic blood pressure, and a pulse oximeter was placed on the right index finger to measure heart rate (HR). MEASUREMENTS AND MAIN RESULTS: Serial blood samples were collected throughout the 24-hour study period to determine clonidine concentrations. The effect of clonidine on blood pressure (BP) and HR also was measured. The half-life, area under the curve, maximum concentration, and time to reach maximum concentration were similar for both the sublingual and oral routes. BP and HR changes were similar for both sublingual and oral clonidine. CONCLUSION: Both routes of administration resulted in similar pharmacokinetic and pharmacodynamic profiles. Attempts to shorten clonidine's latency with sublingual administration were unsuccessful. Our study shows that a single dose of clonidine 0.3 mg has the same pharmacokinetic and dynamic profile when administered orally or sublingually. Therefore, the sublingual route can be predictably used in fasting patients, those having difficulty swallowing, or those who are unable to absorb drugs through the gastrointestinal tract; the sublingual dose is the same as the oral dose.

In vitro protein binding of cefonicid and cefuroxime in adult and neonatal sera.

The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared. Binding parameters for each drug were determined within the concentration range of 25 to 3,000 micrograms/ml. Cefonicid exhibited concentration-dependent protein binding in both types of sera, with more extensive binding in adult serum at all concentrations. Two classes of binding sites were found: a high-affinity, saturable site and a low-affinity, nonspecific site. Cefuroxime also showed two-class, concentration-dependent protein binding in adult serum, but binding in neonatal serum was to a single class and was independent of drug concentration. Parameters for class 1 binding sites for cefonicid indicated one binding site per albumin molecule in both adult and neonatal sera, with association constants of 7.0 x 10(4) and 1.3 x 10(4) M-1, respectively. These parameters were also derived for cefuroxime in adult serum and were 0.15 and 7.1 x 10(4) M-1, respectively. In neonatal serum, the combined value (number of binding sites per molecule x equilibrium association constant) was similar to combined values calculated for class 2 binding sites for cefuroxime in adult serum and for cefonicid in neonatal serum (287 versus 195 and 261 M-1, respectively). Cephalosporins have been shown to compete with bilirubin for albumin binding sites. Lower levels of protein binding of cefuroxime in the therapeutic range may mean a lower potential for drug displacement of bilirubin in neonates, on the basis of these results. It may be prudent to select less highly protein-bound agents when treating neonatal infections.

Stability of Egg White Lysozyme in Combination with Other Antimicrobial Substances.

The effects of pH, ionic strength (I), and selected antimicrobial substances on the lytic activity of egg white lysozyme over an extended storage period of 30 d were studied by observing the rate of clearing of a cell suspension of Micrococcus lysodeikticus . During prolonged storage, lysozyme activity remained relatively stable at pH 7 and ionic strength <0.10, whereas lower activity (P < 0.05) was observed at pH 9 and ionic strength >0.14. Lysozyme activity was highly stable (i.e., maintained over 90% of lytic activity from day 1 to day 30) in solutions of 1.0% sodium chloride, 100 ppm sodium nitrite, 4.0% ethanol, and 100 ppm butylated hydroxytoluene. Lysozyme activity also was stable (i.e., retained over 80% of lytic activity) in solutions of 0.1% sodium benzoate and 100 ppm butylated hydroxyanisol. The lysozyme activity was relatively stable (i.e., retained over 70% of lytic activity) in Solutions of 0.3% calcium propionate, 0.1% potassium sorbate, and 0.1% propyl paraben. About half (50%) of the lysozyme activity was retained in solution of 0.5% EDTA. Activity was lost when lysozyme was combined with 0.5% lactic acid, 4% acetic acid, and 100 ppm chlorine water.

The chemistry of lysozyme and its use as a food preservative and a pharmaceutical.

The chemistry and use of lysozyme as a food preservative and a pharmaceutical are reviewed. Lysozyme inhibits the growth of deleterious organisms, thus prolonging shelf life. Chemicals used to improve the preservative effect of lysozyme and those that inhibit the enzyme are discussed, along with the stability of lysozyme in various chemical environments. Lysozyme has been used to preserve fresh fruits and vegetables, tofu bean curd, seafoods, meats and sausages, potato salad, cooked burdock with soy sauce, and varieties of semihard cheeses such as Edam, Gouda, and some Italian cheeses. Lysozyme added to infant-feeding formulas makes them more closely resemble human milk. Lysozyme has been used clinically in the treatment of periodontitis, administered in chewing gum, and implemented to prevent tooth decay. It has also been administered to patients suffering from cancer for its analgesic effect and has been used as a potentiating agent in antibiotic therapy.

Practical Applications of Food Dehydration: A Review 1, 2.

Removal of water from foods is one of the oldest methods of preserving foods. Today nearly all foods can be preserved by a variety of controlled dehydration processes. Many chemical and physical changes can take place during food dehydration and those changes determine the ultimate quality of the dried and rehydrated product. This review concerns some of the more common drying methods, selected drying processes for various foods and a summary of the nutritive value of dehydrated foods.

Microbiological Aspects of Poultry and Poultry Products - An Update 1, 2.

This update summarizes recent research related to incidence and control of microorganisms contaminating poultry and poultry products. Several reports are cited on numbers and kinds of bacteria likely to be present on poultry carcasses. Discussion includes both pathogenic and spoilage organisms. Studies on lesser known pathogenic bacteria are included. Numerous techniques are described that could disinfect the poultry carcass and extend the shelf life of products. Some of these techniques are not used commercially, but some of the methods discussed could show considerable promise. Further-processed poultry items have been studied less than the refrigerated, ready-to-cook carcass; however, several studies deal with the problems of microbial contamination of cooked, canned, dried or frozen products.

Growth Effect of Sorbate and Selected Antioxidants on Toxigenic Strains of Staphylococcus aureus 1, 2.

Effect of potassium sorbate with and without added antioxidants on Staphylococcus aureus 196, S-6, 137 and 326 in a liquid system was evaluated. We found (a) potassium sorbate a 1, 3, and 5% levels in combination with BHA, BHT, PG (50 and 100 ppm) exerted greater bactericidal and bacteriostatic effects on S. aureus strains at pH 5 than at pH 7; at pH 6 the effect was more pronounced at 3 and 5% compared with 1% sorbate, (b) TBHQ was highly inhibitory to S. aureus strains with or without the addition of sorbate, (c) in combination with sorbate, BHA exerted greater bactericidal effects compared with BHT and PG, (d) higher concentration of antioxidants exerted more bactericidal and bacteriostatic effects on test organisms, (e) S. aureus S-6 was more resistant than 196, 326, and 137 in the presence of sorbate and antioxidants and (f) shake cultures of S. aureus grew better than static cultures in the presence of sorbate and BHA.

Ultrastructure of vitelline membranes from normal and mottled egg yolks.

This study showed that ultrastructure of the vitelline membrane degenerated with degree of yolk mottling. The more severe the mottling the greater the damage to the membrane. The vitelline membrane appears to be composed of three separate structures. The primary matrix (probably collagen) retains its composition until mottling is most severe; then this structure starts to come apart and lose its integrity. The secondary matrix (probably mucin) aids in holding the primary structure in a fixed position. When this structure is removed there is movement in the primary matrix causing large holes to appear. The tertiary matrix (also mucin) is the quickest to disintegrate. The tertiary matrix covers the other structures much like the cuticle around the egg shell. Once it is removed, the remaining structures are open to stress and damage as mottling increases.

Influence of Microwave Radiation on Psychrotrophic Bacteria 1.

Pure cultures of bacteria in nutrient broth at 107 or 108 organisms/ml and various raw meat products were exposed to either 915 or 2450 MHz microwaves. After various timed exposures, temperature increases were noted and samples were removed for plate-count determination of survivors. In nutrient broth, all psychrotrophic bacteria counts were dramatically reduced by short exposure (5 to 20 sec) to microwave radiation. In some instances, initial counts of 107 to 108/ml were reduced to zero after 15 sec of microwave exposure and a temperature of 60 C. Moraxella-acinetobacter (MA-3), Serratia marcescens , Pseudomonas synthaxa , and Alcaligenes viscolactis were extremely susceptible to the microwave treatments. When raw poultry parts, with initial total counts of 104/cm2 of surface area, were exposed to microwave radiation, organisms were reduced by 1 log cycle in 20 sec and by 2 log cycles in 40 sec. Total counts on microwave-treated chicken skin were reduced from 105/cm2 to 103/cm2 in 30 sec. Refrigerated storage of microwave-treated chicken parts indicated that such treatment could substantially increase shelf life.

Effect of Microwaves on Microorganisms in Foods 1, 2.

Microwave cooking has increased in popularity in recent years. Since the time to process food is much shorter than with conventional methods, questions have been raised as to the microbial safety of foods cooked with microwaves. The first part of this review includes discussions on the importance of intrinsic and extrinsic characteristics of foods in relation to destruction of microorganisms in microwave-cooked foods, the mechanism of microwave destruction of microorganisms and viewpoints on the thermal and nonthermal destruction of microorganisms. The second part includes data on the effect of time and temperature on microorganisms in microwave-cooked foods, the effect of microwave destruction of microorganisms in different food systems and the effect of microwaves on different bacteria. The last section includes discussions of destruction of microorganisms by microwave cooking of meats, poultry and egg products, dairy products, cereal products, fruit products, vegetables and miscellaneous foods. We observed that (a) microwave heating of food is more "food dependent" than conventional heating, (b) the manufacturer-recommended microwave treatment time for some foods may not destroy high levels of bacteria, (c) use of microwaves in combination with other conventional heating methods results in more uniform heating in foods and destruction of bacteria, (d) heat generated by microwaves kills naturally-occurring microorganisms as long as the size and type of food are carefully correlated with exposure time, (e) microwaves exert different killing effects on individual bacterial species and (f) the question of thermal versus nonthermal effects of microwaves on microorganisms has not been settled. We believe microwave heating is an important method for processing of foods at home, in institutions and in commercial operations. The process is acceptable from the standpoint of food spoilage and food safety as long as the users understand the limitations and possibilities of microwave heating and are aware of some of the major points presented in this review.

Some effects on layers of sodium sulfate and magnesium sulfate in their drinking water.

Potential for increasing contamination of water supplies with such materials as dissolved inorganic solids suggests more precise water quanlity standards for poultry. Commercial strain S.C.W.L. hens were supplied water containing sodium sulfate (Na2SO4) or magnesium sulfate (MgSO4) (250, 1,000, 4,000, or 16,000 p.p.m.) on a total sulfate basis in Exp. 1 and on a total salt basis in Exp. 2. All data are expressed as percentages deviated from pre-treatment performance. Four thousand p.p.m. of total sulfate as Na2SO4 or MgSO4 significantly depressed feed consumption and hen-day production. Magnesium sulfate (4,000 p.p.m.) had a more depressing effect than Na2SO4 (4,000 p.p.m.) on hen-day production (-80.4 vs. -24.4%). At that level, Na2SO4 significantly increased water consumption and fecal moisture content, while MgSO4 significantly decreased water consumption. All hens on 1l,000 p.p.m. of either salt died during the experiment. No effect on egg quality was observed before the hens died. On a total salt basis (Exp. 2) 16,000 p.p.m. of either Na2SO4 or MgSO4 significantly depressed hen-day production, body weight, and feed comsumption, but increased water consumption. Hens receiving 16,000 p.p.m. Na2SO4 increased water consumption more than those receiving 16,000 p.p.m. MgSO4(146.7 and 24.6%). No significant differences between treatments were observed for mortality (Exp. 2). Mortality data suggest that lethal levels of Na2SO4 and MgSO4 are between 16,000 and 20,032 or 23,680 p.p.m. total salt, respectively.

The influence of dietary nitrate on nitrate concentration in egg yolk and albumen.

Sodium nitrate (from 0 to 2,000 p.p.m.) was added to the drinking water of 32-week old S.C. White Leghorn pullets. Eggs collected once a week for 8 weeks were analyzed for nitrate content. Increasing levels of nitrate in the drinking water resulted in increasing levels of nitrate in albumen and yolk. Higher levels of nitrate were found in the yolk than in the albumen. When birds were started on the experiment, nitrate in the drinking water was reflected by immediate increases in nitrate content of the eggs. The nitrate content of eggs from birds receiving 1,000 p.p.m. NaNO3 (728 p.p.m. NO3-) exceeded the 45 p.p.m. permissible level of nitrate in drinking water for human beings.