Contraindications to use of metformin. Metformin may be useful in gestational diabetes.
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Biomedical subjects
Publications and source records attributed to J Rowan.
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A series of three clinical trials in the oral surgery model evaluated the analgesic efficacy and pharmacokinetics of ketoprofen administered locally as a strategy for decreasing systemic exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). A gel formulation was administered directly into extraction sites 1 hour following oral surgery, and pain intensity was evaluated for 6 hours. Significantly less pain was seen following peripheral administration of both 10 and 30 mg ketoprofen in comparison to the placebo. In a second study, peripheral administration of the 1 mg dose resulted in greater analgesia than oral administration of the same dose formulation or the placebo. The third study demonstrated lower plasma drug levels following the peripheral route of administration in comparison to oral administration of the same dose or ingestion of a 25 mg oral capsule. These data indicate that administration of an NSAID to a peripheral site of tissue injury results in greater analgesia than oral administration and suggests the potential for less drug toxicity through lower circulating drug levels.
OBJECTIVE: To compare the effect of continuous norethindrone acetate (NA)-ethinyl estradiol (EE2) combinations with matching unopposed EE2 or placebo. DESIGN: A 2-year, double-blind, placebo-controlled, parallel-group clinical trial. SETTING: Outpatients at 65 centers. PATIENTS: Asymptomatic or mildly symptomatic women aged 40 years or older who had undergone the onset of spontaneous menopause within the last 5 years and who had an intact uterus. INTERVENTIONS: Patients were equally randomized to placebo or 1 of 8 treatment groups: 0.2 mg of NA and 1 microg of EE2; 0.5 mg of NA and 2.5 microg of EE2; 1 mg of NA and 5 microg of EE2; 1 mg of NA and 10 microg of EE2; 1 microg of EE2; 2.5 microg of EE2; 5 microg of EE2; or 10 microg of EE2. PRIMARY OUTCOME MEASURES: Bone mineral density (BMD) measured by quantitative computed tomography, serum lipids, and endometrial effects as assessed by rate of hyperplasia and proliferative status. RESULTS: Twelve hundred sixty-five patients entered the study. Bone mineral density increased significantly from baseline (P<.001) in the 1 mg NA-5 microg EE2 and the 1 mg NA-10 microg EE2 treatment groups at each annual assessment. Among the unopposed EE2 groups, only the 10-microg group had increased BMD above baseline, but also was accompanied by an unacceptably high rate of endometrial hyperplasia. The NA-EE2 treatment groups had a significant linear dose-response trend for increasing BMD. Increased endometrial proliferation and hyperplasia occurred with increasing unopposed estrogen doses. The combination of NA and EE2 effectively protected the endometrium against hyperplasia. The percentage of change in the ratio of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol was positive for all treatment groups. The increase in triglyceride levels associated with EE2 was attenuated with NA-EE2 treatment. CONCLUSIONS: Daily treatment with NA-EE2 was well tolerated and protected the endometrium from EE2-induced proliferation and hyperplasia. The NA-EE2 treatments produced a dose-related significant increase in BMD that was not present with unopposed EE2 treatment. The overall effect of NA-EE2 treatments on lipid measures was favorable.
AIMS: To study the control, complications and management of prisoners with diabetes on treatment with oral hypoglycaemic agents or insulin in Mt Eden prison, Auckland. METHODS: A cross-sectional study of those prisoners known to be on oral hypoglycaemic agents or insulin by personal interview using a structured questionnaire followed by physical examination and random measurement of fructosamine, lipids and renal function. RESULTS: At the time of the study the prison population was 438 (47 females). Fifty three percent were Maori, 29% European, 14% of Pacific Islands origin and 4% of other nationality. Five males were known to be on oral hypoglycaemics and three further males, also with non-insulin dependent diabetes (NIDDM) were on insulin. Two other males were insulin dependent diabetics (IDDM) aged 22 and 25 years. All were Maori. The mean age (range) of NIDDM patients was 50 (35-68) years. As a group these prisoners were obese with a high prevalence of smoking, hypertension, dyslipidaemia, retinopathy, nephropathy and neuropathy. Four of the five insulin treated patients had been in hospital a total of 11 times in the preceding 12 months for diabetes related health problems accounting for a total hospital stay of 60 days. Three of these prisoners had recurrent self-induced hypoglycaemia or diabetic ketoacidosis. Metabolic control of glucose was however reasonable. CONCLUSIONS: Prisoners known to be on treatment for diabetes have a high prevalence of complications (many previously unrecognised) and display manipulative behaviour. This group requires specialised health care by diabetes trained staff with a knowledge of local prison conditions.
OBJECTIVE: To study the efficacy, microbiologic features and toxicity of prophylactic cefazolin versus prophylactic piperacillin in high-risk patients who undergo open cholecystectomy. DESIGN: Double-blind randomized trial with follow-up for 6 weeks postoperatively. SETTING: An 850-bed community hospital, located in a major Canadian city. Patients admitted to hospital who satisfied published criteria for being at high-risk for infection after open cholecystectomy were entered into the protocol, and those who satisfied the criteria and provided consent were entered into the study. Eighty-one patients were randomly assigned by computer to receive either piperacillin or cefazolin as the prophylactic agent. INTERVENTIONS: Open cholecystectomy. MAIN OUTCOME: Provides detailed information on the organisms found in the biliary tree in patients with acute cholecystitis, assesses the in-vitro activity of cefazolin versus piperacillin against the isolated organisms, expecting that piperacillin would be much more active against isolated anaerobes and gram-negative bacteria. RESULTS: Bactobilia was documented in 42% of patients in the cefazolin group and 29% of patients in the piperacillin group. Piperacillin was active in vitro against 94% of all isolates versus 56% for cefazolin (p < 0.005, McNemar's test). Adverse effects and toxicities in both the piperacillin and cefazolin group were low and were not serious. CONCLUSIONS: Both piperacillin and cefazolin are safe and effective prophylactic antimicrobials for high-risk patients who undergo open cholecystectomy. However, piperacillin had a much wider spectrum of in-vitro activity against the isolated pathogens, especially Enterococcus sp., Enterobacter cloacae and the anaerobes.
In this paper a computer system for cervical screening call and recall based on the Community Health Index (CHI) population data-base is described. It allows the unscreened population to be identified and located on an individual general practice basis. The results of the call programme on 9517 women aged 20-60 years listed on the CHI and with no record of a cervical smear is described. There was a 24% smear uptake in the call programme which meant that after the call programme the total population cover had risen from 71% to 78%. In addition, if women with a valid reason are excluded, and the data-base corrected for women no longer in the area, the true cover rises to 88%. An analysis of the percentage cover in each GP practice is described with the implications for implementation of screening targets for primary care.
OBJECTIVE: To compare computed tomography and magnetic resonance imaging in investigating patients suspected of having a lesion in the posterior cranial fossa. DESIGN: Randomised allocation of newly referred patients to undergo either computed tomography or magnetic resonance imaging; the alternative investigation was performed subsequently only in response to a request from the referring doctor. SETTING: A regional neuroscience centre serving 2.7 million. PATIENTS: 1020 Patients recruited between April 1986 and December 1987, all suspected by neurologists, neurosurgeons, or other specialists of having a lesion in the posterior fossa and referred for neuroradiology. The groups allocated to undergo computed tomography or magnetic resonance imaging were well matched in distributions of age, sex, specialty of referring doctor, investigation as an inpatient or an outpatient, suspected site of lesion, and presumed disease process; the referring doctor's confidence in the initial clinical diagnosis was also similar. INTERVENTIONS: After the patients had been imaged by either computed tomography or magnetic resonance (using a resistive magnet of 0.15 T) doctors were given the radiologist's report and a form asking if they considered that imaging with the alternative technique was necessary and, if so, why; it also asked for their current diagnoses and their confidence in them. MAIN OUTCOME MEASURES: Number of requests for the alternative method of investigation. Assessment of characteristics of patients for whom further imaging was requested and lesions that were suspected initially and how the results of the second imaging affected clinicians' and radiologists' opinions. RESULTS: Ninety three of the 501 patients who initially underwent computed tomography were referred subsequently for magnetic resonance imaging whereas only 28 of the 493 patients who initially underwent magnetic resonance imaging were referred subsequently for computed tomography. Over the study the number of patients referred for magnetic resonance imaging after computed tomography increased but requests for computed tomography after magnetic resonance imaging decreased. The reason that clinicians gave most commonly for requesting further imaging by magnetic resonance was that the results of the initial computed tomography failed to exclude their suspected diagnosis (64 patients). This was less common in patients investigated initially by magnetic resonance imaging (eight patients). Management of 28 patients (6%) imaged initially with computed tomography and 12 patients (2%) imaged initially with magnetic resonance was changed on the basis of the results of the alternative imaging. CONCLUSIONS: Magnetic resonance imaging provided doctors with the information required to manage patients suspected of having a lesion in the posterior fossa more commonly than computed tomography, but computed tomography alone was satisfactory in 80% of cases...
For many years Tayside has benefited from a successful opportunistic cytology screening programme. In recent years, however, the decrease in mortality due to cervical cancer has levelled off, with most cases of severe disease arising in women who have not been screened. In view of this the health board developed a new computer system for call and recall based on the community health index. This facility allowed the unscreened population to be identified and located on an individual general practice basis. The findings of the call programme in the 3136 women aged 50-60 were studied. The 29 practices in Perth and Kinross participated in the scheme. Before the call started 4287 out of 7423 (58%) women had been screened, and after the call programme this had risen to 5109 (69%). Moreover, a further 1158 (15%) women were identified who had a valid reason for exclusion from the programme. This meant that 6267 (84%) women of the study population were accounted for by the system. The call programme in Tayside will be completed in 1989 and will include all women aged 20-60.
Magnetic resonance imaging was used to measure intracranial extraventricular and ventricular cerebrospinal fluid (CSF) volume. In 10 normal subjects lateral ventricular and extraventricular intracranial CSF volumes were 25.3 +/- 4.6 ml (mean +/- SD) and 97.6 +/- 6.6 ml, respectively (total 122.8 +/- 38.7). These volumes were measured in 4 patients and the results were: 11.0 ml ventricular volume, 68.7 ml total cranial CSF in the patient with benign intracranial hypertension; 606.6 ml ventricular, 174.1 ml total in the patient with hydrocephalus due to a blocked ventriculo-peritoneal (V-P) shunt; 83.4 ml ventricular, 108.5 ml total in the patient with normal pressure hydrocephalus; and 52.7 ml ventricular, 181.0 ml total in the patient with cerebral atrophy due to Alzheimer's disease. The technique gave highly reproducible results (SD less than 5.7% of mean value). It may be useful in differential diagnosis and as an objective means of monitoring therapy or progress in conditions such as cerebral atrophy, hydrocephalus, and benign intracranial hypertension.
The effects of transdermal nitrate (TN) (Transiderm-Nitro TTS, Geigy Pharmaceuticals, one 10 cm2 patch daily) and oral isosorbide dinitrate (ISDN) (Sorbitrate, Stuart Pharmaceuticals, 10 mg three times daily) were compared in a group of 20 patients with chronic stable angina pectoris. Treadmill exercise duration was prolonged from a median time of 365 s to 428 s after ISDN (P less than 0.05), but was unchanged after TN. The difference between the active treatments was not significant. Weekly consumption of glyceryl trinitrate (GTN) increased during treatment with TN from a median value of 5.5 to 6.3 (P less than 0.05). A decrease was observed after ISDN (7.8 to 3.9, P = NS), and the difference between the drugs was significant (P less than 0.01). Systolic arterial pressure was significantly lower during the ISDN than during the TN treatment period in both the supine (135 +/- 5 vs 128 +/- 5 mm Hg; P less than 0.05) and standing positions (134 +/- 5 vs 122 +/- 5 mm Hg; P less than 0.05). No change in weekly attack rate, the degree of ST depression at angina on treadmill testing, or the number of episodes of ST depression recorded during a 24 h period by Holter monitoring was observed after either drug. In this study, an antianginal effect was demonstrated for ISDN but not for TN. It is suggested that the dose of TN may have been inadequate to demonstrate such an effect, and further studies using a higher dose schedule will be required.
The electrical excitability of the cortex was monitored during craniotomy in 10 patients with ruptured aneurysms, to test their ability to tolerate hypotensive anesthesia. Excitability was assessed by measuring the direct cortical response, a response evoked and recorded from the surface of the brain. Previous animal experiments had shown that this response can be used as an index of cerebral blood flow. In the 10 patients the response progressively declined as the blood pressure was lowered and increased when the pressure was restored. Observation of the direct cortical response during aneurysm operations is a practical method for evaluating the electrophysiological responsiveness of the cortex during hypotension, and the authors suggest that decreases in the amplitude of the response are related to decreased in local cerebral blood flow.
The association of Streptococcus mutans with human dental decay was investigated by using several types of samples: (i) paraffin-stimulated saliva samples taken from children with from 0 to 15 decayed teeth; (ii) pooled occlusal and approximal plaque taken from children with no decayed or filled teeth, or from children with rampant caries of 10 or more teeth; (iii) plaque removed from single occlusal fissures that were either carious or noncarious. The results showed a significant association between plaque levels of S. mutans and caries. The strongest association, P < 0.0001, was found when plaque was removed from single occlusal fissures. Seventy-one percent of the carious fissures had S. mutans accounting for more than 10% of the viable flora, whereas 70% of the fissures that were caries free had no detectable S. mutans. Sixty-five percent of the pooled plaque samples from the children with rampant caries had S. mutans accounting for more than 10% of the viable flora, whereas 40% of the pooled samples from children that were caries free had no detectable S. mutans. Saliva samples tended to have low levels of S. mutans and were equivocal in demonstrating a relationship between S. mutans and caries.
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A technique is described which utilises the full analysis and display capabilities of a commercial MRI system to produce digital maps of multi-parameter functions produced by MR contrast theory. The technique is utilised to determine the effects of nominating specific overall scan times on the optimum solutions as produced by the theory and it is shown that different solutions are obtained when the theory is applied using typical clinical constraints. The digital mapping approach is potentially of great value in prospectively determining pulse timing parameters to produce optimum contrast images, in producing contrast maps to aid retrospective image interpretation, and as a training aid for clinicians inexperienced in the interpretation MR images.
A new technique is described that utilises a novel magnetic resonance pulse sequence to produce a quantitative index both for ventricular and, for the first time, extraventricular intracranial CSF volumes. The pulse sequence is a combination of a null-point inversion recovery sequence with an extended spin-echo read (echo time = 400 ms), which produces a contrast of CSF to white or grey matter of approximately 120:1. A series of experiments are performed on phantoms representing CSF filled ventricles and sulci over a wide range of volume values, and it is found that the standard deviation of differences between true and estimated values is 3.9% for ventricles, 4.6% for total cranial CSF, and 7.9% for CSF within the sulci. Normal volunteer reproducibility studies revealed corresponding standard deviations of less than 5.5%. Using the technique to produce absolute estimates of CSF volumes in normal subjects and patients produced results in good agreement with previously published necropsy studies. The technique has wide neurological and neurosurgical applicability particularly in terms of differential diagnosis and as an objective monitor of therapy or progression in conditions such as hydrocephalus, atrophy, and benign intracranial hypertension.
A review of 15 recent publications purporting to provide the relaxation times of CSF reveals a considerable disparity in the quoted results, by a factor of five in terms of T1 (range 1,000 to 5,500 ms) and by a factor of 16 for T2 (range 166 to 2,640 ms). In this article measurements are performed independently on both a spectrometer and an imager. The results indicate that for CSF T1 is greater than 3,000 ms and T2 is approximately 2,000 ms at 6 MHz. The vast differences in relaxation behaviour between CSF and other body tissues have considerable clinical implications and present profound diagnostic opportunities. The application of this knowledge to ventriculography, myelography, and image contrast methodology is discussed.
OBJECTIVE: To determine whether there is a significant reduction in frequency and severity of hot flashes in symptomatic postmenopausal women who are administered continuously different dose combinations of norethindrone acetate and ethinyl estradiol. DESIGN: Two randomized clinical trials (Study 1 and Study 2) were conducted in which study participants recorded in daily diaries the frequency of their hot flashes. Study 2 participants also recorded the number of mild, moderate, or severe hot flashes they experienced. In Study 1, a total of 219 postmenopausal women reporting vasomotor symptoms were placed randomly into groups to receive either a placebo or 1 of 4 treatments (0.2 mg/1 microg; 0.5 mg/2.5 microg; 1 mg/5 microg; or 1 mg/10 microg norethindrone acetate/ethinyl estradiol). In Study 2, a total of 266 highly symptomatic postmenopausal women were placed randomly to receive either a placebo or 1 of 3 treatment groups [0.5 mg/2.5 microg; 1 mg/5 microg; or 1 mg/10 microg norethindrone acetate (NA)/ethinyl estradiol (EE)]. Total duration of treatment was 16 weeks in Study 1 and 12 weeks in Study 2. Study 1 subjects had to have at least 10 hot flashes during the week before randomization. Study 2 subjects had to have at least 56 moderate to severe hot flashes during the week before randomization. RESULTS: In both studies, there was a dose-related decrease in hot flash frequency with the highest dose (1 mg NA/10 microg EE) group that had the greatest response. Significant differences from placebo (p < 0.05, Dunnett's test) occurred within 4 weeks in Study 1 for hot flash frequency with a percent reduction in frequency ranging from 33% for placebo to 84% for both the 1 mg NA/10 microg EE and 1 mg NA/5 microg EE dose groups. Likewise, Study 2 significant reductions in hot flash frequency occurred by Week 2 for 1 mg NA/10 microg EE, Week 3 for 1 mg NA/5 microg EE, and Week 5 for 0.5 mg NA/2.5 microg EE (p < 0.05, Dunnett's test). This dose effect was also apparent with regard to severity. In addition, more subjects had clinically meaningful reductions in hot flash frequency or elimination as the dose combinations increased. CONCLUSION: There were significant reductions in hot flash frequency and severity with continuous treatment with norethindrone acetate and ethinyl estradiol combinations. The time at which significant reductions were observed, as well as the magnitude of the response, were dose dependent. The opportunity for lower-dose options of a new continuous-combined hormone replacement therapy provides therapeutic flexibility for women who are recently menopausal.