Referrals, Wait Times and Diagnoses at an Urgent Neurology Clinic over 10 Years.

BACKGROUND: An urgent neurology assessment clinic was created at our institution to improve access to prompt neurological assessment, and has been in operation for over a decade. We assessed its timeliness and impact. METHODS: The clinic database was examined retrospectively for trends in the volume and waiting time to assessments, neurologic diagnoses, and whether neurologic assessment changed patients' diagnoses. Before and after implementation, the frequency of emergency department neurology assessments and hospital admissions for neurological investigation were compared. RESULTS: In the first decade, 25145 referrals were received; 12460 patients were accepted and assessed within an average of 3.8 working days. The most common problems seen included headache and seizure (20.2% each). Overall, 44.6% of assessments resulted in a change to the referring diagnosis; this proportion varied by the type of problem seen (from 10.5% for seizures to 92.5% for psychiatric disturbances). From the pre- to post-opening periods, there were fewer emergency room neurological assessments (35.7% reduction) and fewer hospital admissions for neurological investigation (4.4/week to 2.2/week, 50% reduction). CONCLUSIONS: The urgent neurology clinic model at our institution has provided excellent service, including wait times of a few days, to a catchment of over two million Canadians for over a decade; clinic assessments have affected diagnoses and patient care.

Immunological and C-peptide studies of patients with diabetes in northern Ethiopia: existence of an unusual subgroup possibly related to malnutrition.

AIMS/HYPOTHESIS: Surveys in northern Ethiopia have demonstrated that apparent type 1 diabetes occurs more frequently than elsewhere in Africa and, indeed, in other parts of the world. We therefore investigated in detail a cohort of diabetic patients from this region to clarify the nature of this type of diabetes. METHODS: All patients attending the diabetic clinic at Mekelle Hospital in the Tigray region of northern Ethiopia were investigated over a 6 week period. Clinical, demographic and anthropometric data were collected, as well as measurements of HbA(1c), fasting lipid profile, fasting serum C-peptide and serum markers of beta cell autoimmunity, i.e. islet antigen-2 and GAD antibodies (GADA). RESULTS: Of 105 patients seen, 69 (66%) were on insulin treatment and had been from or close to diagnosis. Their median age and diabetes duration were 30 and 5 years, respectively, with a male excess of 2:1. Median BMI was 20.6 kg/m². Despite these clinical characteristics suggestive of type 1 diabetes, only 42 of 69 (61%) patients were C-peptide-negative and 35% GADA-positive. Overall, 38 (36%) of the total group (n = 105) had immunological or C-peptide characteristics inconsistent with typical type 1 or type 2 diabetes. The clinical characteristics, local prevalence of undernutrition, and GADA and C-peptide heterogeneity suggest a malnutrition-related form of diabetes. CONCLUSIONS/INTERPRETATION: Not all patients in northern Ethiopia with apparent type 1 diabetes appear to have the form of disease seen in Europids; their disease may, in fact, be related to malnutrition.

Investigation and management of severe hyponatraemia in a hospital setting.

AIMS: To evaluate the assessment and management of severe hyponatraemia in a large teaching hospital. METHODS: Inpatients with serum sodium <125 mmol/l were identified prospectively from a laboratory database over a six month period. Notes were examined and data extracted. Case notes were carefully reviewed retrospectively by a consultant endocrinologist with regard to accuracy of the diagnosis and the appropriateness of investigations and management. RESULTS: 104 patients with a serum sodium <125 mmol/l were identified. Mean (SD) age was 69 (14), 52% were female, mean hospital stay was 16 (12) days, and overall mortality 27%. Adequate investigations were rarely performed. Only 28 (26%) had plasma osmolality measured, 29 (27%) urine osmolality, 11 (10%) urinary sodium, 8 (8%) plasma cortisol, and 2 (2%) a short Synacthen test. Comparing the "ward" and "specialist review" diagnoses, there were significant discrepancies for "no cause found" (49% v 27%, p<0.001), alcohol (6% v 11% p<0.01), and syndrome of inappropriate antidiuresis (20% v 32%, p = 0.001). Treatment was often illogical with significant management errors in 33%. These included fluid restriction and intravenous saline given together (4%) and fluid restriction in diuretic induced hyponatraemia (6%). Mortality was higher in the group with management errors (41% v 20% p = 0.002). CONCLUSION: Severe hyponatraemia is a serious condition, but its investigation and evaluation is often inadequate. Some treatment patterns seem to be arbitrary and illogical, and are associated with higher mortality.

Apolipoprotein B gene polymorphisms are associated with lipid levels in men of South Asian descent.

Three polymorphic sites of the apolipoprotein B gene - the insertion/deletion signal peptide, XbaI and EcoRI sites - were examined in a sample of 107 healthy men and in 46 men with evidence of coronary heart disease selected from a large population survey of South Asians aged 40-69 in London, U.K. There were no significant differences in allele frequencies between cases and controls. Frequencies of the ins (insertion) and X- (absence of XbaI cutting site) alleles were higher in South Asians than in Europeans studied previously (South Asians versus Europeans ins: 0.80 vs. 0.68, P less than 0.025; X-: 0.71 vs. 0.47-0.56, P less than 0.001). The del allele was associated with higher levels of total cholesterol (P less than 0.05) and the X+ allele with lower levels of HDL cholesterol (P less than 0.05), and thus both polymorphisms were associated with differences in the ratio of HDL cholesterol to total cholesterol (ins/del, P less than 0.01; XbaI, P less than 0.001). Mean waist-hip girth ratio was lower in the 10 men homozygous for the X+ allele than in the 42 men with X-/X+ and 55 men with X-/X- genotypes; the means (+/- SEM) were 0.92 +/- 0.02, 0.97 +/- 0.01 and 0.96 +/- 0.01 respectively (P = 0.03). These data suggest that genetic variation in linkage disequilibrium with the XbaI and ins/del polymorphisms of the apo B gene contributes to the determination of total cholesterol and HDL cholesterol levels and possibly to obesity in South Asians.

Restriction fragment length polymorphisms in the apo B gene in relation to coronary artery disease.

We have determined the frequencies of the alleles at the EcoRI (E), XbaI (X) and PvuII (P) polymorphic restriction sites in the apo B gene in 124 white men with coronary artery disease (CAD) and in 146 white men free from CAD. The frequencies of the E- (restriction site absent) and X- alleles were both significantly higher in normocholesterolaemic men with CAD than in those without CAD, but the frequency of the P+ allele (restriction site present) was similar in the 2 groups. The frequency of the E- allele was significantly higher in CAD men with hypertriglyceridaemia than in normal men without hypertriglyceridaemia. In the normocholesterolaemic men without CAD, the mean serum cholesterol concentration was higher in those with genotype X++ than in those with genotype X--. Mean serum LDL-apo B and LDL-cholesterol concentrations did not differ significantly between men with different XbaI or EcoRI genotypes. Serum apo A-I levels differed significantly between normal men with different XbaI genotypes. Serum HDL-cholesterol levels differed significantly between CAD men with different XbaI genotypes. These results suggest that in white men the E- and X- alleles are in linkage disequilibrium with a nearby allele that is causally related to CAD. It is also possible that the amino acid substitution at position 4154 in apo B, brought about by the nucleotide change responsible for the EcoRI polymorphism, has a direct effect on the atherogenicity of LDL.

Apolipoprotein A-I gene polymorphisms: frequency in patients with coronary artery disease and healthy controls and association with serum apo A-I and HDL-cholesterol concentration.

We have investigated the association between serum high density lipoprotein-cholesterol (HDL-C) and apo A-I concentration and the PstI and XmnI restriction fragment length polymorphisms of the apolipoprotein AI-CIII-AIV multigene complex. Two groups of subjects were examined. The first comprised 174 unrelated male patients under 60 years of age with angiographic evidence of coronary artery disease (CAD). Of this group 34 were non-North European. The second group consisted of 104 unrelated healthy male North European subjects aged under 60 and free from demonstrable CAD, who attended a health screening clinic in London. For the PstI polymorphism, the frequency of the rarer P2 allele was 0.12 in both the North European and non-North European patients and this was higher than in the control group (P2 frequency 0.06, P less than 0.05). Healthy individuals with the genotype P1P2 had higher levels of apo A-I but similar levels of HDL-C compared to those with the genotype P1P1. However, CAD patients with the genotype P1P2 had lower serum levels of apo A-I and significantly lower serum levels of HDL-C compared to those with the genotype P1P1 (0.85 mmol/l vs. 1.0 mmol/l, P less than 0.05). The allele frequencies of the XmnI polymorphisms were not significantly different in the control group and the group of North European patients, although within the sample of non-North European patients, the frequency of the X2 allele was significantly higher than that found in the North European controls (0.26 vs. 0.09). Patients with the genotype X1X2 had a higher mean serum concentration of HDL-C and apo A-I compared with patients with the genotype X1X1 (1.14 and 0.93 mmol/l for HDL-C, P less than 0.05; 147 and 123 mg/dl for apo A-I, P less than 0.05). Associations between HDL-C and apo A-I levels and PstI and XmnI genotype were similar in patients taking and not taking beta-blockers. The data show that genetic variation in the apo AI-CIII-AIV gene cluster is associated with coronary artery disease although only weakly, and suggest that the mechanism of this association may operate through an effect in determining the serum concentration of apo A-I and HDL-cholesterol.

Hexetidine ('Oraldene'): a report on its antibacterial and antifungal properties on the oral flora in healthy subjects.

A randomized, double-blind crossover trial, in 10 adult healthy subjects, was carried out to compare the antibacterial and antifungal activity of a 0.1% solution of hexetidine with that of placebo. The pre-dosing oral flora of the subjects was assessed from saliva samples cultured for aerobic and anaerobic bacteria, as well as Candida albicans. Subjects then rinsed their mouths for 1 minute 3-times a day with 15 ml 0.1% hexetidine or placebo, saliva samples being collected at 2 minutes, 30 minutes, 1 hour, 3 hours and 5 hours post-dosing. Dosing was continued for 8 consecutive days on each treatment with an intervening wash-out period of 1 week. Hexetidine reduced aerobic bacterial counts on Day 1 and Day 8 by a maximum of 83% and 86%, respectively, at 2 minutes post-dosing. The reductions were statistically significantly lower than placebo up to 1 hour post-dose on Day 1 and up to 3 hours post-dose on Day 8. Similarly for anaerobic bacterial counts, 92% and 88% maximum reductions were recorded on Day 1 and Day 8, which again were significantly lower than placebo for up to 3 hours post-dose. For Candida albicans, however, the maximum reduction was 91% on the first day and 67% on Day 8, maintained for 30 minutes post-dosing. Although not eradicating completely aerobic and anaerobic bacteria, it is concluded that the substantial reduction in their numbers should prove clinically useful.

Ideological conflicts between clients and psychotherapists.

Clients come to psychotherapy with their own theories of how their problems are to be solved. These ideas fall into five categories: relationship rescue, will power, vindication, bromide, and spiritualistic theories. Many of the classic disputes which arise between clients and therapists can be attributed to differences in their theories of cure.

Diabetic complications and glycaemic control in remote North Africa.

BACKGROUND: Delivery of diabetes services in resource-poor areas of Africa is difficult. Control is often poor and complications are common. However, adequate robust surveys are uncommon, particularly in remote rural areas. This makes needs assessment difficult and health-care planning impossible. AIM: To accurately assess the glycaemic control and burden of complications in a group of diabetic patients from a remote area of a resource-limited north African country. DESIGN: Prospective cohort study. METHODS: Over a 6-week period, all patients attending the diabetic clinic at Mekelle Hospital in northern Ethiopia were intensively assessed, using imported western technology as necessary. Glycated haemoglobin (HbA(1c)), lipid profile, serum creatinine and urinary albumin-creatinine ratio were measured. Complications were assessed as accurately as possible, including examination of fundi by an ophthalmic specialist, and biosthesiometry for neuropathy. RESULTS: There were 105 patients, mean (+/- SD) age 41 +/- 16 years and diabetes duration 7 +/- 6 years. There were 74 (70%) males, and 69 (66%) on insulin. Median body mass index was low at 20.6 kg/m(2), but mean HbA(1c) high at 11.3 +/- 2.8% (68% had an HbA(1c) over 10.0%). Cataract (12%), retinopathy (21%), neuropathy (41%) and microalbuminuria (51%) were common; but nephropathy (2%) was rare, as was large vessel disease (6% had peripheral vascular disease, and none had coronary artery disease or cerebrovascular disease). Risk factors such as hypertension (5%) and smoking (2%) were uncommon, and lipid profiles were generally good. DISCUSSION: We conclude that in this severely resource-limited area of North Africa, glycaemic control amongst diabetic patients is very poor. Neuropathy, retinopathy and microalbuminuria are common; but large vessel disease risk factors are beneficial, and macroangiopathy prevalence is low. Scattered populations, shortage of drugs and insulin and lack of diabetes team care are major factors behind these serious issues of diabetic control and complications.

Clinical and biological aspects of acid phosphatase.

The identity and genetic origins of the nonspecific orthophosphate monoesterases with an acid pH optimum--the acid phosphatases--are now becoming clear. They form a family of genetically distinct isoenzymes, many of which show significant posttranslational modification. Four true isoenzymes exist. The erythrocytic and lysosomal forms show widespread distribution and are expressed in most cells; in contrast, the prostatic and macrophagic forms have a more limited expression. The erythrocytic and macrophagic forms are distinguished from the others in resisting inhibition by dextrorotatory tartrate. The prostatic form has long been used as a marker for prostatic cancer and the macrophagic forms have been linked with miscellaneous disorders, notably increased osteolysis, Gaucher's disease of spleen, and hairy cell leukemia, whereas the normal levels of intravesical lysosomal acid phosphatase in I cell disease pointed the way toward the mechanisms underlying its intracellular processing.

High prevalence of hypertriglyceridaemia and apolipoprotein abnormalities in coronary artery disease.

Serum lipids and apolipoproteins A-I and B were measured in 174 men aged less than 60 with angiographically confirmed coronary artery disease and in 572 healthy control men. Two thirds of the patients had raised age-corrected values of fasting serum cholesterol and/or triglyceride and/or a low high density lipoprotein (HDL) cholesterol compared with the controls. Eighteen (30%) of the 61 normolipidaemic patients had a concentration of serum apolipoprotein A-I below the 5th percentile of 233 controls. In normolipidaemic patients on beta blockers the relative prevalence of serum low density lipoprotein (LDL)-apolipoprotein B values above the 95th percentile of 339 controls was significantly increased. Discriminant function analysis showed that a raised concentration of serum triglyceride was the best discriminant between patients and controls, with raised LDL-apolipoprotein B and reduced apolipoprotein A-I coming second only to triglyceride in analyses where each was separately compared with all the lipid variables. These associations were highly significant and were independent of other influences, including beta blockade. These findings re-emphasise the importance of hypertriglyceridaemia as a risk factor and confirm that apolipoprotein abnormalities occur frequently in coronary disease, even in normolipidaemic patients.

Hypoalphalipoproteinaemia and polymorphisms associated with reduced expression of the apolipoprotein A-I gene and resolution of disputed paternity in a large English family.

A Pst-I RFLP polymorphism adjacent to the 3' end of the apolipoprotein A-I gene is reported to associate with hypoalphalipoproteinaemia with dominant inheritance in families identified through accelerated coronary heart disease. This association was not apparent in a large English family identified through voluntary health screening, and with no evident premature coronary disease. Any association could, however, be masked by sex, or by further undetermined variation affecting Pst-I restriction sites. Analysis of this and other polymorphisms present also led to resolution both of disputed paternity and of a long-standing family feud.

An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease.

OBJECTIVE: The insulin tolerance test (ITT) is usually regarded as the 'gold standard' for the assessment of the hypothalamic-pituitary axis (growth hormone (GH) and ACTH) but must be used with caution and is contra-indicated in certain groups of patients. The glucagon stimulation test (GST) has previously been shown to be a good alternative when the ITT is contra-indicated and like the ITT stimulates both GH and ACTH secretion. There is however limited data on the use of the GST in patients with hypothalamic-pituitary disease. DESIGN AND PATIENTS: An audit of 500 GST was performed in 374 patients with hypothalamic-pituitary disease. Glucagon was administered via the subcutaneous route and bloods were taken at times 0 90 120 150 180 210 and 240 minutes. RESULTS: In the vast majority peak GH (84.4%) and cortisol (93%) responses occurred between 120 and 180 minutes Little information was obtained from the 240 minute sample. The medical supervision required was minimal and the side-effects encountered during this test were mild; 20% of the tests were associated with nausea occasionally with vomiting sweating or headaches. Four patients fainted but recovered quickly. CONCLUSIONS: This large audit has shown that the glucose stimulation test is well tolerated and can easily be performed in an out-patient setting with minimal medical supervision. The 240 minute sample added little additional information and could be omitted.

Elderly people with hypothalamic-pituitary disease and growth hormone deficiency: lipid profiles, body composition and quality of life compared with control subjects.

OBJECTIVE: In healthy adults the secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) declines with ageing and body composition alters, particularly with an increase in total body fat. In elderly people, hypothalamic-pituitary disease can cause GH deficiency (GHD), compared with age matched controls. This study aimed to clarify whether GHD in the elderly is associated with differences in body composition, circulating lipid levels and quality of life (QOL) compared with control subjects. SUBJECTS: Twenty-seven elderly patients (14 males, mean age 71 years, range 65-83) with hypothalamic-pituitary disorders (23 pituitary tumours) and GHD (mean (SD) peak stimulated GH response 1.6 mIU/l (1.03) range 0.6-5) were studied. Twenty-five patients had been treated surgically (six cranial surgery, 19 transsphenoidal) and eight patients had received external cranial irradiation. Twenty-seven control subjects (14 males, mean age 72 years, range 65-86) were also studied. METHODS: Weight, body mass index (BMI), total fat mass (FM, bioelectrical impedance), waist to hip ratio (WHR), serum IGF-1, fasting blood glucose and lipid profile were measured. QOL was assessed in both groups using five interviewer administered self-rating questionnaires: The Nottingham Health Profile, Short-Form 36, Hospital Anxiety and Depression Scale, Mental Fatigue Questionnaire and Life Fulfilment Scale. The GHD group also completed the Disease Impact Scale. RESULTS: The data (mean (SD)) from males and females were analyzed separately. The male patients had a higher BMI than controls, 28.9(4.5) vs. 25.2(2.3) kg/m2 (P = 0.01) but the BMI in the female patients and controls was similar. In the female patients compared with the controls, FM was higher 39. 4(6) vs. 33.1(8.3) % (P = 0.02), WHR was also higher 0.9(0.08) vs. 0. 83(0.09) (P = 0.03) and serum IGF-1 levels were lower 10.8(6.4) vs. 18.2(6.5) nmol/l (P = 0.01). However, in the male patients, FM, WHR and IGF-1 levels were similar to the controls. Fasting blood glucose was similar in both male and female patients and the controls. Two female patients and one male control subject were taking lipid-lowering agents and were therefore excluded from the analysis of lipid profiles. Total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol and total cholesterol/HDL cholesterol ratio were not significantly different for both male and female patients compared with the controls. The 27 patients with GHD reported significantly less energy (P < 0.05), mobility (P < 0.05) and personal life fulfillment (P < 0.01) than the 27 controls. There were significantly more problems with emotional reaction (P < 0.01), social isolation (P < 0.05) and mental fatigue (P < 0.05). Additionally the GHD group reported more impairment in areas of social functioning (P < 0.05), general health (P < 0.05) and mental health (P < 0.05). The GHD group reported a modest degree of disease impact (mean score of 14.1). There were no significant differences in the domains of material life fulfillment, pain, sleep, physical functioning, vitality, anxiety, depression, self-esteem or role physical functioning compared with the controls. CONCLUSION: Compared with control subjects, the elderly female patients with hypothalamic-pituitary disease and GHD had a significantly higher total fat mass, with the WHR indicating a more central fat distribution and lower female serum IGF-1 levels. In contrast, elderly male patients had similar total fat mass, WHR and IGF-1 levels compared to the controls. There were no significant differences in the lipid profiles between male or female patients compared to controls. However, many of the male patients were receiving androgen replacement which might have influenced these results. Low HDL cholesterol concentrations are probably a better predictor of future cardiovascular disease than raised LDL cholesterol levels in the elderly population and these were similar in patients and controls for both

Diabetic complications and glycaemic control in remote North Africa

Background: Delivery of diabetes services in resource-poor areas of Africa is difficult. Control is often poor and complications are common. However, adequate robust surveys are uncommon, particularly in remote rural areas. This makes needs assessment difficult and health-care planning impossible. Aim: To accurately assess the glycaemic control and burden of complications in a group of diabetic patients from a remote area of a resource-limited north African country. Design: Prospective cohort study. Methods: Over a 6-week period, all patients attending the diabetic clinic at Mekelle Hospital in northern Ethiopia were intensively assessed, using imported western technology as necessary. Glycated haemoglobin (HbA1c), lipid profile, serum creatinine and urinary albumin­creatinine ratio were measured. Complications were assessed as accurately as possible, including examination of fundi by an ophthalmic specialist, and biosthesiometry for neuropathy. Results: There were 105 patients, mean (± SD) age 41 ± 16 years and diabetes duration 7 ± 6 years. There were 74 (70%) males, and 69 (66%) on insulin. Median body mass index was low at 20.6 kg/m2, but mean HbA1c high at 11.3 ± 2.8% (68% had an HbA1c over 10.0%). Cataract (12%), retinopathy (21%), neuropathy (41%) and microalbuminuria (51%) were common; but nephropathy (2%) was rare, as was large vessel disease (6% had peripheral vascular disease, and none had coronary artery disease or cerebrovascular disease). Risk factors such as hypertension (5%) and smoking (2%) were uncommon, and lipid profiles were generally good. Discussion: We conclude that in this severely resource-limited area of North Africa, glycaemic control amongst diabetic patients is very poor. Neuropathy, retinopathy and microalbuminuria are common; but large vessel disease risk factors are beneficial, and macroangiopathy prevalence is low. Scattered populations, shortage of drugs and insulin and lack of diabetes team care are major factors behind these serious issues of diabetic control and complications