Effects of agitation on size distribution of particulate matter in large-volume parenterals

The particle-size distributions of six types of large-volume parenterals subjected to different degrees of agitation were determined using an automatic particle counter. Data acquired from each solution, which had been maintained in a stored condition, subjected to agitation by inverting 20 times, and then mechanically shaken for 30 min, produced a linear relationship between log N greater than D and log D. Both the slope (K) and the number of particles per milliliter exceeding 1 micrometer in diameter (N greater than 1) exhibited a dependence on the degree of agitation. Their combined effect indicates that agitation by 20 hand inversions removed particulate matter from the surface of the container, which increased the total number of particles in solution (greater than 1 micrometer) but did not significantly alter the relative size distribution. Agitation for 30 min, however, disintegrated agglomerates and produced a particle-size distribution with a greatly increased number of particles whose diameters were less than 1 micrometer and a corresponding decrease in the number of particles exceeding 1 micrometer in diameter. The particle-size distribution of a parenteral solution determined by this in situ instrumental method was, therefore, dependent upon the degree of agitation to which the parenteral was subjected prior to examination.     

The artificial heart. Progress and promise

A multidisciplinary group has designed, fabricated, and evaluated an artificial heart. The heart consists of two smooth-surfaced sac-type pumps, two pneumatic power units, and an electronic control system. The artificial heart has been employed in 22 calves. A variety of problems have been encountered and overcome and a significant improvement in pump design has been made. As a result, a gradual increase in survival times has occurred. The last two calves in which the heart was tested lived for 60 and 42 days respectively. These animals ate well and gained weight. The ability of the control system to balance the output of the two pumps over long periods of time and to automatically increase cardiac output with treadmill exercise has been confirmed. No insurmountable problems in the development of the artificial heart have been identified. The date that an artificial heart will be available for clinical use depends on the availability of funds and on the tenacity of the investigators.     

Selective inhibition of the monosynaptic spinal reflex by a series of hydroxylated alkylaminoindans

5-Hydroxy-2-piperidino-4,5,6,7-tetrahydroindan (5) and a number of related tetrahydro and dihydro compounds were prepared by selective mono- and dihydroxylation of the dihydro products from the Birch reduction of various alkylaminoalkylindans, tetralins, benzenes, and isoindolines. Some of these compounds showed a remarkably selective inhibition of monosynatpic spinal reflex in the segmental cat preparation.     

The clinical assessment of cancer tests: a statistical approach to the prediction of "false positive" rates from controls

As the sensitivity of the new in vitro cancer detection techniques increases, a larger number of "false positive" results can be expected from control populations apparently free from malignant disease at the time of the test. An attempt is made to predict the number of unexplained positives, together with the expected age and sex distribution, using published cancer registration statistics. The predicted numbers are compared with the observed numbers of unexplained positives in two clinical trials of the MEM test.     

Fatal systemic mycotic infections in the burned child

Two cases of systemic phycomycotic burn wound infection occurred in severely burned children. Both patients, although treated aggressively, died after systemic colonization through the burn wound by fungi. Modern burn therapy has increased survival of many severely burned children but opportunistic fungal infection remains as an ominous threat. Early recognition, wide excision or amputation, and systemic antifungal agents comprise the current clinical armamentarium against systemic fungal invasion of burn wounds.     

Effects of nasal packing on eustachian tube function

Eustachian tube function was assessed by tympanometry in 47 patients (94 ears) with anterior nasal packing placed after nasal surgery and in 12 patients (24 ears) requiring anterior and posterior packing for epistaxis. Twenty-four of the 94 ears (25.5%) in patients with anterior packing exhibited reductions in middle ear pressure (greater than or equal to --100 mm H2O), whereas 12 of 13 ears (92.3%) ipsilateral to and six of 11 ears (45.4%) contralateral to the posterior pack demonstrated comparable reductions in middle ear pressure. The observation that posterior packing is associated with a greater incidence of eustachian tube dysfunction than anterior packing suggests that the mechanism of this dysfunction may be related to stasis in the peritubal lymphatic plexus rather than to nasal obstruction per se.     

Modification and abolition of re-entry within the His-Purkinje system in man by diphenylhydantoin

The phenomenon of macrore-entry (Re) within the His-Purkinje system (HPS) was consistently observed in 10 of 19 patients during retrograde refractory period studies. Effects of intravenous infusion of diphenylhydantoin (DPH) on Re were studied in these 10 patients 10 minutes after completion of infusion (mean plasma level equal to 17.0 microgram/ml). Diphenylhydantoin modified determinants of Re in seven patients (group I) and abolished Re in the remaining three patients (group II). In group I, DPH shortened the critical V1 V2 from 310.0 +/- 30.5 to 292.9 +/- 25.6 msec (P less than 0.025) and critical V2 H2 intervals for Re from 201.4 +/- 18.4 to 185.0 +/- 13.8 msec (P greater than 0.05). In group II, DPH abolished Re in two of three patients by precluding attainment of critical V2 H2 intervals whereas Re was abolished in the remaining one patient despite attainment of critical V2 H2 intervals (vs control). For both groups, DPH significantly shortened functional and effective refractory periods of the HPS (P less than 0.001 and less than 0.01, respectively) without significantly affecting the effective refractory period of the ventricular muscle. Diphenylhydantoin either completely abolished or significantly shortened the retrograde gap zones in the HPS. It is concluded that diphenylhydantoin significantly shortens His-Purkinje system refractoriness, abolishing Re in the patients with higher degree of improvement in refractoriness.     

Ulnar nerve palsy in Paget's disease

A 73-year-old housewife with enlargement of her distal right humerus and especially the medial epicondyle due to Paget's disease developed an ulnar nerve palsy. Transposition of her ulnar nerve anterior to her elbow completely relieved her symptoms. A similar case of ulnar nerve palsy associated with expansion of the distal humerus due to Paget's disease seems not to have been previously reported.     

Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers

Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NH-C(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies.     

Adenoma characteristics at first colonoscopy as predictors of adenoma recurrence and characteristics at follow-up. The Polyp Prevention Study Group

In Bacillus transformation, sexual isolation is known to be an exponential function of the sequence divergence between donor and recipient. Here, we have investigated the mechanism under which sequence divergence results in sexual isolation. We tested the effect of mismatch repair by comparing a wild-type strain and an isogenic mismatch-repair mutant for the relationship between sexual isolation and sequence divergence. Mismatch repair was shown to contribute to sexual isolation but was responsible for only a small fraction of the sexual isolation observed. Another possible mechanism of sexual isolation is that more divergent recipient and donor DNA strands have greater difficulty forming a heteroduplex because a region of perfect identity between donor and recipient is required for initiation of the heteroduplex. A mathematical model showed that this heteroduplex-resistance mechanism yields an exponential relationship between sexual isolation and sequence divergence. Moreover, this model yields an estimate of the size of the region of perfect identity that is comparable to independent estimates for Escherichia coli. For these reasons, and because all other mechanisms of sexual isolation may be ruled out, we conclude that resistance to heteroduplex formation is predominantly responsible for the exponential relationship between sexual isolation and sequence divergence in Bacillus transformation.