Prevention of precipitation of phenytoin in an infusion fluid by hydroxypropyl β-cyclodextrin

Injection of phenytoin is often diluted with infusion fluids before administration, which may lead to precipitation of the drug due to changes in pH and/or vehicle. It is not possible to add cyclodextrins to the original injections to prevent precipitation of the drug, because the quantities required would be impractical (>100% w/v). However, from a knowledge of the solubility of phenytoin in cyclodextrin solutions, it is possible to add sufficient amounts of a soluble cyclodextrin to infusion fluids to maintain the solubility of phenytoin after the original injection is diluted to clinical concentrations in the fluid. From solubility measurements, theoretical amounts of hydroxypropyl β-cyclodextrin (HPCD), sufficient to prevent precipitation of phenytoin, were added to 0·9% w/v sodium chloride solution, adjusted to pH 7·0. Phenytoin injection was diluted to clinical concentrations in the cyclodextrin/NaCl solutions. The mixtures, together with analogous mixtures containing phenytoin, but no HPCD, were stored at 25 °C for 3 days. In the presence of the cyclodextrin no precipitates of phenytoin were observed, but in its absence an immediate massive precipitation of phenytoin occurred. This is a flexible method for using soluble cyclodextrins to prevent precipitates of drugs in infusion fluids, provided the cyclodextrin used is not toxic.     

Gastric emptying patterns of a liquid meal in newborn infants measured by epigastric impedance

Epigastric impedance was used to measure the gastric emptying patterns of a liquid non-caloric meal (5 mL water kg⁻¹) in 30 healthy newborn infants. Twenty-six mature infants were examined in the first eight days of life, and four preterm infants were examined within 6 weeks after birth. The recordings consisted of two components: the emptying signal (the DC component), and a phasic 3 cycles per minutes (CPM) signal (the AC component). In some of the infants the phasic 3 CPM signal was also seen during the fasting state.
For mature infants the median half emptying time (T₅₀) was 6.9 min. For a second meal given within one hour after the first meal the half emptying time was 5.5 min ( P  < 0.01). In preterm infants the emptying times were not significantly different from mature infants.
Day-to-day variation was low with a coefficient of variation of 17% in nine infants.
A periodic change of the impedance signal, the phasic 3 CPM signal, was observed after a meal in 24 of the infants. The median frequency was 3.0 CPM in 20 mature and 2.9 CPM in four preterm infants. In nine infants a phasic 3 CPM signal was also observed during the fasting state, with a median frequency of 2.9 CPM.
Measurement of gastric emptying pattern with epigastric impedance is a simple investigation for the evaluation of gastric emptying time and phasic activity in mature and preterm infants. However, the method is sensitive to spontaneous movements of the children, resulting in non-valid measurements in around one fourth of the infants.     

Spectral analysis of intercycle heart fluctuations in the diethyl-ether-anaesthetized or pithed rat treated with l-hyoscyamine

1 Within the context of neural regulation of the activity of sinus node pacemaker cells, the study of heart rate variability, as explored in the frequency domain by spectral analysis, was proposed about 15 years ago as a quantitative tool for the evaluation of short-term autonomic cardiovascular control. It has since been postulated that the two main oscillations observed, one at low and the other at high frequency, may respectively be markers of sympathetic vs. vagal efferent cardiac activity, and that the low- and high-frequency signals may reflect a reciprocal or ‘push–pull’ relationship between sympathetic and parasympathetic control. 2 In our power spectra assessment, ECG R–R intervals were submitted to fast Fourier transformation analysis in order to study the mechanisms underlying the control of heart beats in rats. Data were acquired in conditions of steady arterial blood pressure and cardiac and respiratory activity (spontaneous or artificially stimulated) in diethyl-ether-anaesthetized and pithed rats, as well as in a group of control rats, all in the presence and absence of l-hyoscyamine. 3 With increasing doses of the parasympathetic antagonist, the fractal dimension of the time-series structure remained stable in most cases. The low-frequency spectral component narrowed with increasing drug doses and the high-frequency band underwent either no, or only very slight, changes. 4 In these rodent assays, the low- and high-frequency signals cannot be interpreted as a push–pull relationship between sympathetic and parasympathetic control.     

The effects of a 0.12% chlorhexidine-digluconate-containing mouthrinse versus a placebo on plaque and gingival inflammation over a 3-month period

Abstract Several previous studies have evaluated the effects of 0.12% chlorhexidine digluconate (ChD) mouthrinses on plaque and gingival inflammation. However, previously, none have been based in general dental practices. The aim of this study was to evaluate the potential to conduct controlled periodontal clinical trials in co-operation with general dental practitioners (gdps). The project took place in 5 general dental practices in the South of England. 121 healthy subjects (24 at 4 sites and 25 at the 5th). aged 18-65 years, mean 35 ± 12) years participated in a double-blind, randomised study during which they received full mouth assessments for plaque and gingival bleeding at baseline, 6 and 12 weeks. 60 subjects were randomly asigned to use the 0.12% ChD mouth wash and 6i the placebo. The assessments were carried out by 5 gpds, who had previously achieved inter-examiner κ scores of 0.78–0.85 (mean 0.81) for the plaque index (PlI), and of 0.73–0.94 (mean 0.87) for a modified gingival index (mGI), and who maintained κ scores of 0.51–0.90 for PII and of 0.73–1.00 for mGI during the 12 months required to complete the study. 98 subjects (48 ChD and 50 placebo) completed the study. Even though the baseline levels of plaque and gingivitis were low, by week 12, mean whole mouth piaque score of the ChD mouthwash users had fallen from 1.33 at baseline to 0.96 and was significantly lower (p < 0.001) than for the placebo users, 1.31 at baseline to 1.13. Whole-mouth gingival bleeding score fell from 0.56 to 0.42 in the ChD mouthwash group but was unchanged (0.54–0.55) in the placebo group. A subsidiary data analysis which considered the effects at sites indicated that within these overall differences, the ChD users experienced almost 2× the reduction from plaque score 2 at baseline at proximal molar sites over a 12-week period (50.6% ChD versus 27.6% placebo). It was concluded that 0.12% ChD mouthwash reduced plaque accumulation fay 28% and gingival inflammation by 25% over a 12–week period, that it is feasible for a group of gdps to maintain high levels of inter–examiner consistency in the use of PlI and mGI, that it is also feasible to carry out such a multicentre study in general dental practice, and that the use of mean mouth scores per subject to analyse the effects of mouthrinses may well mask variations in response throughout the mouth.     

Infectivity of African cassava mosaic virus clones to cassava by biolistic inoculation

Summary.  Clones of an African cassava mosaic virus isolate originating from Nigeria (ACMV-NOg) were shown to be infectious to cassava by biolistic inoculation. The production of pseudorecombinants between ACMV-NOg and clones of an ACMV isolate originating from Kenya (ACMV-K) indicated that the lack of infectivity of ACMV-K to cassava was due to defect(s) in the DNA B genomic component; this component encodes two proteins involved in cell-to-cell movement. This is the first demonstration of infectivity of a cloned geminivirus to cassava and conclusively proves that ACMV is the causative agent of cassava mosaic disease. The potential uses of infectious ACMV clones and the means by which to introduce them into cassava are discussed. Received January 18, 1998 Accepted May 27, 1998     

Puncture wound related pseudomonas infections of the foot in children

Eleven children with Pseudomonas aeruginosa infection complicating foot puncture wounds were reviewed. Delay in presentation (mean 2 days) and diagnosis (mean 9 days) due to a paucity of clinical signs of deep infection was characteristic of this condition. Septic arthritis (5 patients) and osteomyelitis (3 patients) were frequent complications. Treatment involved multiple surgical debridements and prolonged intravenous antibiotic therapy. The clinical outcome was good although long-term radiographic changes were common.     

The Family System Test (FAST)

The impact of a cancer diagnosis upon a family has become a focus of clinical interest, but few scientific studies have been completed in this area. The objectives of this pilot study were twofold: first, to test the applicability of the Family System Test (FAST) in families (n=5) with a young adult member with cancer and secondly to evaluate patterns of interactions within these families. Results show that the FAST is applicable and useful to evaluate the different perceptions of hierarchy and cohesion - two essential variables - within these families. The great majority of family members represented their relationships as balanced (i.e., cohesive and moderately hierarchical). However, contrary to nonclinical families, fathers had a less positive view than mothers and patients: fathers more often perceived family and parenteral relations as unbalanced, and also more often perceived a reversal of hierarchy and a cross-generational coalition within the family. Implications for future research and clinical care are discussed.     

Deep Granuloma Annulare (Pseudorheumatoid Nodule) in Children: Clinicopathologic Study of 35 Cases

Deep granuloma annulare (DGA) is one of several lesions of skin and superficial soft tissues whose histologic character is a palisading granuloma with a small central focus of necrosis or necrobiosis. Unlike the other palisading necrobiotic lesions, DGA has a predilection for children in the first 5 to 6 years of life. A painless subcutaneous nodule(s) in the lower anterior tibial region or foot and the scalp, typically in the occiput, was the most common presenting feature in this study of 35 cases. Additional or recurrent lesions were reported in approximately 70% of cases with clinical follow-up. All lesions showed the presence of necrobiosis; however, one of the characteristic features was the multinodular character of the predominantly mononuclear cellular aggregates. The presence of vascular spaces at the periphery of the nodular profiles served as a clue to the diagnosis of DGA. The palisading arrangement of the mononuclear cells was evident only in those foci with central necrobiosis. A histiocytic disorder or fibrohistiocytic process was a common consideration in the differential diagnosis, especially in those cases with less apparent foci of necrosis. Palisading histiocytes with prominent eosinophilic cytoplasm and some nuclear atypism were problematic with regard to possible epithelioid sarcoma. Our study failed to identify any underlying or predisposing factors in the development of DGA. Despite the fact that DGA is a well-documented lesion in children, it occurs sufficiently infrequently that it is often not considered clinically when it presents as a subcutaneous mass or masses in a child. Its recognition by the pathologist is especially important as the occurrence of additional lesions in a high proportion of children can be anticipated without undue concern. Received June 16, 1997; accepted October 28, 1997.     

Pharmacokinetics of orally administered norethisterone enanthate in rabbit, monkey, and women

Norethisterone enanthate (NET-En), an established intramuscular long-acting contraceptive agent, has previously been shown to be effective in inhibiting fertility in two rodent species even 4 days after oral ingestion. Pharmacokinetics of NET and NET-En were studied after oral and intramuscular doses in two animal species and a few women. The results suggest that the NET-En was absorbed within a day in all the species after oral dose. The estimates of relative bioavailability ranged from 13 to 51% in rabbits, monkeys, and women. The elimination half-life was 5–10 days. The presence of the active component, NET, in the circulation over the experimental period of 15 days suggests that NET-En could be useful as a long-acting oral pill. The suppression of progesterone levels during the luteal phase of menstrual cycle in women also supports this finding.     

Immunohistochemical differentiation of metastases of renal carcinomas versus other carcinomas with anti-γGT monoclonal antibody 138H11

Aims : Adenocarcinomas account for about 60% of metastatic cancers of unknown primary (CUP) site. In such a clinical CUP situation, histopathologists are challenged to differentiate renal cell carcinomas (RCC) from other adenocarcinomas with similar immunophenotypes, especially chemotherapeutically treatable mammary and ovarian carcinomas. Methods and results : Recently, we produced a monoclonal antibody (mAb), designated 138H11, against human gamma-glutamyltransferase (γGT), which stained over 98% primary clear cell and chromophilic RCC on frozen sections. The 138H11 epitope could not be stained using conventional techniques in most paraffin-embedded sections of the same origin, due to destruction by formalin fixation below the detection level. Here, we demonstrate that mAb 138H11 can specifically stain γGT in paraffin-embedded primary and metastatic RCC after enhancement with an ultrasensitive immunohistochemical method. We analysed a selected subgroup of adenocarcinomas with immunophenotypes which would not allow a differentiation from RCC in a CUP situation. We found a predominantly membranous expression of the 138H11 target antigen in 26/51 primary RCC and 15/34 metastatic RCC. In contrast, all 43/43 primary ovarian and bronchial carcinomas as well as 54/54 metastases of ovarian, mammary, bronchial and gastric carcinomas were negative for mAb 138H11. Conclusions : The data suggest that mAb 138H11 is useful for the immunohistochemical differentiation of RCC from other metastatic adenocarcinomas if the primary site of the tumour is not known.