Calcium needs of adolescents

Adolescents grow at the greatest rate of any age group after infancy and accumulate 37% of their total bone mass during this growth spurt. Because maximum bone mass is acquired during adolescence, the calcium deposited during adolescence determines the risk of osteoporosis and fracture in adulthood. Bone mass is dependent on calcium intake, growth and pubertal development, exercise, and genetic and racial factors. Unfortunately, during this time of tremendous calcium need, most adolescents eat a diet that is very deficient in calcium. Girls are twice as likely to be deficient as boys (85% vs 43%). Other factors contributing to poor bone mineralization include adolescent pregnancy, anorexia nervosa, excessive exercise, and various chronic medical conditions. To avoid osteoporosis in later life, adequate dietary calcium intake should be recommended and calcium supplementation considered in all adolescent patients.     

Multistate case-control study of maternal risk factors for neonatal group B streptococcal disease. The Active Surveillance Study Group

Risk factors for early onset disease (EOD) caused by Group B streptococci (GBS) that are the foundation of prevention guidelines were identified in studies conducted in a few hospital centers. We investigated cases of EOD identified through laboratory-based active surveillance during 1991 and 1992 in a multistate population of 17 million. Ninety-nine cases were compared with 253 controls matched for hospital, date of birth and birth weight. Prematurity (< 37 weeks of gestation) was present in 28% of cases; 53% of case mothers had rupture of membranes > 12 hours; and 48% reported intrapartum fever. The incidence of EOD in each surveillance area was higher among blacks. By multivariate analysis, case mothers were more likely than controls to have rupture of membranes before labor onset (adjusted odds ratio 8.7, P < 0.001), intrapartum fever (adjusted odds ratio 11.9, P < 0.001), and history of urinary infection during pregnancy (adjusted odds ratio 4.3, P < 0.05). Young maternal age was also associated with risk of disease. Three-fourths of case mothers had intrapartum fever, < 37 weeks of gestation and/or prolonged rupture of membranes, indicators previously used to select high risk women for intrapartum chemoprophylaxis. Our findings extend data from single hospitals and suggest prenatal screening and selective intrapartum chemoprophylaxis of high-risk mothers could potentially prevent the majority of EOD in the United States.     

Solution structure and backbone dynamics of component IV Glycera dibranchiata monomeric hemoglobin-CO

The solution structure and backbone dynamics of the recombinant, ferrous CO-ligated form of component IV monomeric hemoglobin from Glycera dibranchiata (GMH4CO) have been characterized by NMR spectroscopy. Distance geometry and simulated annealing calculations utilizing a total of 2550 distance and torsion angle constraints yielded an ensemble of 29 structures with an overall average backbone rmsd of 0.48 A from the average structure. Differences between the solution structure and a related crystal structure are confined to regions of lower precision in either the NMR or X-ray structure, or in regions where the amino acid sequences differ. 15N relaxation measurements at 76.0 and 60.8 MHz were analyzed with an extended model-free approach, and revealed low-frequency motions in the vicinity of the heme, concentrated in the F helix. Amide proton protection factors were obtained from H-D amide exchange measurements on 15N-labeled protein. Patterns in the backbone dynamics and protection factors were shown to correlate with regions of heterogeneity and disorder in the ensemble of NMR structures and with large crystallographic B-factors in the X-ray structures. Surprisingly, while the backbone atoms of the F helix have higher rmsds and larger measures of dynamics on the microsecond to millisecond time scale than the other helices, amide protection factors for residues in the F helix were observed to be similar to those of the other helices. This contrasts with H-D amide exchange measurements on sperm whale myoglobin which indicated low protection for the F helix (S. N. Loh and B. F. Volkman, unpublished results). These results for GMH4 suggest a model in which the F helix undergoes collective motions as a relatively rigid hydrogen-bonded unit, possibly pivoting about a central position near residue Val87.     

Reflections on the culture of the preimplantation embryo

There has been a considerable improvement in the media available for the culture of preimplantation mouse embryos during the 40 years since mouse embryos were first cultured and successfully transferred to uterine foster mothers. Two new media, KSOM and mMTF, are becoming more commonly used. The history of the development of these media, including recent work on KSOM and mMTF, is reviewed. A major artefact in the earlier work was the two-cell block. The causes of the two-cell block and the methods by which it has been overcome are reviewed. It is concluded that even the best available media inevitably cause imbalances in the environment in which the embryos are forced to develop, because they consist of only a small subset of the compounds present in the natural environments. As a result, the embryos must adapt to these abnormal conditions if they are to survive. The implications of these conclusions on the choice of media for specific purposes are discussed.     

Lidocaine toxicity in primary afferent neurons from the rat

Evidence from both clinical studies and animal models suggests that the local anesthetic, lidocaine, is neurotoxic. However, the mechanism of lidocaine-induced toxicity is unknown. To test the hypothesis that toxicity results from a direct action of lidocaine on sensory neurons we performed in vitro histological, electrophysiological and fluorometrical experiments on isolated dorsal root ganglion (DRG) neurons from the adult rat. We observed lidocaine-induced neuronal death after a 4-min exposure of DRG neurons to lidocaine concentrations as low as 30 mM. Consistent with an excitotoxic mechanism of neurotoxicity, lidocaine depolarized DRG neurons at concentrations that induced cell death (EC50 = 14 mM). This depolarization occurred even though voltage-gated sodium currents and action potentials were blocked effectively at much lower concentrations. (EC50 values for lidocaine-induced block of tetrodotoxin-sensitive and -resistant voltage-gated sodium currents were 41 and 101 microM, respectively.) At concentrations similar to those that induced neurotoxicity and depolarization, lidocaine also induced an increase in the concentration of intracellular Ca++ ions ([Ca++]i; EC50 = 21 mM) via Ca++ influx through the plasma membrane as well as release of Ca++ from intracellular stores. Finally, lidocaine-induced neurotoxicity was attenuated significantly when lidocaine was applied in the presence of nominally Ca(++)-free bath solution to DRG neurons preloaded with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Our results indicate: 1) that lidocaine is neurotoxic to sensory neurons; 2) that toxicity results from a direct action on sensory neurons; and 3) that a lidocaine-induced increase in intracellular Ca++ is a mechanism of lidocaine-induced neuronal toxicity.     

A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide

BACKGROUND: The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design. In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3 x 4 factorial trial of bisoprolol, a beta 1-selective adrenergic blocking agent, and hydrochlorothiazide. METHODS: A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial. RESULTS: The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo. CONCLUSIONS: The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.     

Castleman''s disease in the extremity

Castleman's disease is an uncommon entity that is characterized by lymphoid hyperplasia with two variants: the hyaline vascular type and the plasma cell type. We present a case affecting the lower extremity, an extremely rate site of the disease.     

Port site electrosurgical (diathermy) burns during surgical laparoscopy

BACKGROUND: Direct and capacitive coupling of diathermy current have been reported as causes of occult injury during surgical laparoscopy. METHODS: In order to determine the incidence of electrosurgical injury adjacent to metal and plastic cannulas, skin biopsies at 19 port sites used for monopolar electrosurgery were analyzed for coagulative necrosis. Prior to surgery the cannulas were randomized to either metal or plastic. RESULTS: Coagulative necrosis was observed at nine electrosurgery port sites compared to only one control (chi2 = 4.872; df = 1; 0.05 > p > 0.02). Plastic cannulas afforded no greater protection from skin burns than metal cannulas. CONCLUSIONS: Burns may be the result of direct or capacitive coupling to metal cannulas or capacitive coupling to the skin edge across plastic cannulas. The potential exists for burns to other tissues also in close proximity to a cannula used for electrosurgery.     

Nitrogen metabolism of sheep and goats consuming Acacia brevispica and Sesbania sesban

We described the effects of two East African browses, Acacia brevispica and Sesbania sesban, on nitrogen metabolism of sheep and goats. The A. brevispica had a substantial amount of proanthocyanidins (condensed tannins); S. sesban did not. The browses were fed at three levels in combination with vetch (Vicia dasycarpa) and teff straw (Eragrostis abyssinica). Fecal N, N balance, and plasma urea N (PUN) were estimated with intact animals. Ruminal ammonia (RuA) and VFA concentrations were estimated with ruminally fistulated animals. Urinary N loss, PUN, RuA, and VFA concentrations were higher for S. sesban diets than for A. brevispica diets. Fecal N was highest with diets including A. brevispica due to high levels of fecal neutral-detergent insoluble N. Nitrogen retention was highest for diets including S. sesban. Nitrogen retention was adequate for A. brevispica diets because low urinary N compensated for high fecal N. Four hypotheses describe possible effects of tannins on N metabolism: 1) escape of protein from the rumen to the lower tract; 2) increased microbial yield; 3) increase in N-containing endogenous products; and 4) protein made indigestible in tannin-protein complexes. The effect of tannins in A. brevispica on N metabolism can best be described by the formation of indigestible tannin-protein complexes, although increased production of endogenous products is also possible.