Importance of storing emergency serum samples for uncovering murder with insulin.

A case of a previously healthy 48-year-old man murdered by exogenous insulin administration is reported. The patient was delivered unconscious to the emergency unit. Initially, treatment with hyperbaric oxygen was commenced because decompression sickness was suspected. However, the treatment was aborted as the patient was found to be hypoglycaemic (nadir serum glucose 0.3 mmol/l) and treatment and diagnostics of hypoglycaemia commenced. Brain damage due to hypoglycaemia was severe, and the patient remained in a vegetative state for 2 months before he died of multiorgan failure. Serum samples drawn at admittance were stored frozen, whereby it was possible to show retrospectively, that while the concentration of insulin in serum was high (75 mU/l, increasing further to over 240 mU/l in the next few hours) concentration of C-peptide was low (below detection limit of 0.1 nmol/l) at the hypoglycaemic stage. It was concluded that the patient had received exogenous insulin somehow, and the police was informed. Circumstantial evidence obtained during ensuing criminal investigation was considered by the court to prove the patient's wife (a nurse) guilty of murder. The availability of stored frozen serum samples drawn at the early stage of hospitalization helped to uncover the crime involved in our case.

Preanalytical and analytical factors affecting laboratory results.

The results of laboratory tests have a substantial role in the diagnostics of diseases. However, laboratory results do not always correspond with the patient's clinical status. They may be unexpected and surprising. On the other hand, an abnormal laboratory result may be accepted as such and interpreted as a sign of a disease. However, an abnormal result may result from several factors other than disease. Conventionally, these interfering factors have been divided into preanalytical and analytical factors and furthermore into factors acting in vivo and in vitro. The list of these factors is long and laborious to bear in mind. In this review we focus on the factors which, in practice, most often affect laboratory results in healthy individuals and which explain an unexpected result.

Response of serum total renin to ramipril and metoprolol in hypertensive patients.

Renin-angiotensin system has long been thought to be a classic endocrine negative feedback system in the pathophysiology of hypertension. Furthermore, angiotensin II formation was believed to be regulated by renin secreted from the kidneys. In contrast to these considerations is the identification of local angiotensin II production in other tissues than pulmonary vasculature. Prorenin, the molecular precursor of renin, has been assumed to be involved in local angiotensin II production because of its renin-like activity. Prorenin has also been found to be secreted from extrarenal sources, although a major part of it is derived from the kidneys. Increased concentration of total renin in serum has been proposed to be useful in identifying patients with active proliferative retinopathy in insulin-dependent diabetic patients. Renin-angiotensin system is strongly affected by angiotensin-converting enzyme (ACE) inhibitors and therefore the interfering effect of ACE inhibitor medication on total renin concentration should be known in order to interpret serum total renin concentrations. Nine hypertensive outpatients, all men, treated at the department of internal medicine in Turku University Central Hospital, received randomly 5 mg of ramipril or 95 mg of metoprolol once a day for 4 weeks. Ramipril significantly increased the mean value of total renin (191.9 ng/l vs 312.0 ng/l, p < 0.01), but the metoprolol-induced increase in the concentration of serum total renin was insignificant. We conclude that the negative feedback mechanism in regulating renin and prorenin secretion was inhibited by ACE inhibitor ramipril but beta 1-selective adrenoceptor antagonist metoprolol did not significantly change total renin concentration in serum.

Laparoscopic instillation of hyperosmolar glucose vs. expectant management of tubal pregnancies with serum hCG < or = 2500 mIU/mL.

OBJECTIVE: To compare expectant management with local instillation of 50% glucose solution for tubal pregnancies with a serum hCG level < or = 2500 mIU/mL. DESIGN: Prospective, non-randomized, comparative clinical study. SETTING: Two university departments. PATIENTS: One hundred and twenty-eight patients with laparoscopically-confirmed tubal pregnancy and serum hCG < or = 2500 mIU/mL. INTERVENTIONS: Eighty patients in Graz were treated with laparoscopic instillation of 50% glucose solution and 48 patients in Turku were followed expectantly. MAIN OUTCOME MEASURES: Resolution of hCG excretion, need for further interventions. RESULTS: Seventy-four of the 80 patients (92%) in the glucose group (32 of 33 with an initial hCG < or = 250 mIU/mL and 42 of 47 with hCG 251-2500 mIU/mL) and 36 of 48 (75%) patients in the expectant group (19 of 23 with an initial hCG < or = 250 mIU/mL and 17 of 25 with hCG 251-2500 mIU/mL) had resolution of the pregnancy with no further intervention (p=0.008, chi-square test, odds ratio 0.24). CONCLUSIONS: Glucose instillation is superior to expectant management for patients with early tubal pregnancy.

Effects of ramipril on the hormone concentrations in serum of hypertensive patients.

The effects of the angiotensin-converting enzyme inhibitor ramipril on thirteen endocrinological tests were evaluated. These tests comprised serum follitropin, lutropin, prolactin, thyrotropin, free thyroxine, total thyroxine, free triiodothyronine, parathyrin, cortisol, testosterone, sex hormone binding globulin, androstenedione and dehydroepiandrosterone sulphate. Eleven hypertensive outpatients, 9 men and 2 women, treated at the department of internal medicine in Turku University Central Hospital, received 5 mg of ramipril once a day for the study period of four weeks. The above mentioned endocrinological tests were performed before and at the end of the ramipril treatment. Ramipril decreased the value of free thyroxine statistically significantly, p = 0.011, from the mean value of 17.1 pmol/l to the mean value of 16.0 pmol/l when measured with Amerlex-MAB* free thyroxine kit. The mean within-subject difference was -1.10 pmol/l with a 95% confidence interval of -1.87 - -0.33 pmol/l. With the AutoDELFIA free thyroxine kit and with the reference method dialysis+RIA no effect was detected. Other endocrinological tests examined were not affected by ramipril. Since the decreasing effect of ramipril on free thyroxine was detected only with Amerlex-MAB* but neither with AutoDELFIA nor with dialysis+RIA, the effect was concluded to be analytical. The underlying mechanism and the component ultimately interfering with the analysis is unknown.

A medication database--a tool for detecting drug interactions in hospital.

OBJECTIVE: Drug interactions may lead to life-threatening injuries. More often, however, they lead to slow recovery, induce slight symptoms or result only in potential injury. Therefore, clinicians are not always aware of using potentially interacting drug combinations. An on-line alarming system of potential drug interactions was developed in Turku University Central Hospital. In the present study, we utilised the system to find out the incidence and nature of potential drug interactions occurring in a representative hospital patient population. METHODS: Computerised anatomical therapeutic chemical (ATC)-coded patient medication data of 2547 patients, treated in two internal medicine wards, were combined with an ATC-coded rule base of drug interactions. All potential drug interactions in the study population were searched for. RESULTS: A total of 326 potentially serious drug interactions were detected in the study population. The number of patients in this group was 173, i.e. 6.8% of all patients had one or several drug combinations which might have led to serious clinical consequences. Concomitant use of calcium and fluoroquinolones (decreased absorption) was the most common mistake (66 prescriptions). CONCLUSIONS: Potentially inappropriate drug combinations seem to occur frequently. Structured and coded medication data can be utilised efficiently to detect potential drug interactions in hospital. Computerised online monitoring and automatic alarming of potentially hazardous drug combinations might help clinicians to prescribe more safely, but further development of the system is needed to avoid unnecessary alarms.

Computerized monitoring of potentially interfering medication in thyroid function diagnostics.

OBJECTIVE: Many drugs are known to affect the results of laboratory tests. This may cause problems in the interpretation of clinical laboratory data and lead to wrong diagnoses, unnecessary further tests and additional costs. A computerized monitoring system of potential drug effects on laboratory tests was developed in Turku University Central Hospital. In the present study the incidence and nature of potentially interfering drug effects in thyroid function diagnostics was examined in order to ease the clinical implementation of the system. METHODS: Computerized medication data of 754 hospital in-patients whose thyroid function was tested were combined with a knowledge base of drug effects on laboratory tests. All medications that potentially affected the levels of serum thyrotropin or free thyroxin in study patients were detected. RESULTS: 40% (292 of 735) of the patients tested for thyrotropin and 32% (107 of 333) of the patients tested for free thyroxin received potentially interfering medication during the tests. The most common potentially interfering medication was acetylsalicylic acid, but the daily dose was usually low, 100 mg. CONCLUSIONS: The coincidence of potentially interfering medication and thyroid function tests was substantial. On-line hints of drug effects on thyroid function tests might offer valuable decision support to clinicians, but further development of the system is needed to regulate the prevalence of warnings into a clinically optimal level.

Elevated serum total renin is insensitive in detecting incipient diabetic nephropathy.

OBJECTIVE: To assess the influence of incipient diabetic nephropathy on the levels of total renin in serum. RESEARCH DESIGN AND METHODS: Fifty-five adult patients with insulin-dependent diabetes mellitus (IDDM) were examined in a cross-sectional study. The main outcome measures were serum total renin concentration and urinary albumin excretion rate. RESULTS: The total renin concentrations in serum were significantly (P < 0.05) higher in 12 patients with microalbuminuria than in 43 patients without albuminuria, but this difference was significant only in men. There was a significant but weak positive correlation between urinary albumin excretion rate and serum total renin concentration in all patients (r = 0.412, P < 0.05, n = 55), but the sensitivity of high serum concentrations of total renin in detecting incipient nephropathy was low (17%). In the study group, two of the three patients suffering from proliferative retinopathy had the highest total renin concentrations in serum. CONCLUSIONS: Microalbuminuric patients have higher mean serum total renin concentrations than normoalbuminuric patients, but because of low sensitivity, high total renin concentration cannot be used for screening incipient diabetic nephropathy.

Microalbuminuria. Invalidity of simple concentration-based screening tests for early nephropathy due to urinary volumes of diabetic patients.

OBJECTIVE: To evaluate the possibility of replacing quantitative albumin excretion rate (AER) measurements with rapid screening tests for microalbuminuria. RESEARCH DESIGN AND METHODS: Dipstick-negative specimens from 363 consecutive insulin-dependent diabetes mellitus (IDDM) and 46 non-insulin-dependent diabetes mellitus (NIDDM) patients from primary-care and hospital clinics (11% inpatients) within the district of Turku University Hospital were studied. Albumin concentrations and 12-h nightly excretion rates (N-AER) were measured by nephelometry (sensitivity 2 mg/L). RESULTS: An increased N-AER (greater than 15 micrograms/min) was seen in 99 IDDM (27%) and 15 NIDDM (33%) patients. The median urinary volume was 900 ml/12 h, with a maximum of 3000 ml. At the level of 20 mg albumin/L, the sensitivity to detect elevated N-AER was 70% among IDDM patients and 60% among NIDDM patients. At a lower albumin concentration of 10 mg/L, the sensitivities were increased to 91 and 87% in IDDM and NIDDM patients, respectively, but the specificities were reduced to 77 and 71%, respectively. CONCLUSIONS: To evaluate incipient nephropathy, we recommend quantitative measurements of N-AER from timed urine collections only. Dipstick tests are either insensitive or nonspecific.

Glucagon-stimulated and postprandial plasma C-peptide values as measures of insulin secretory capacity.

Basal, postprandial (2 h after breakfast), and glucagon-stimulated plasma C-peptide concentrations were determined in a group of 36 adult diabetic patients. Basal and postprandial C-peptide values were measured on consecutive days to estimate the degree of variation of C-peptide secretion. In a subgroup of 15 diabetic patients treated chronically with diet and oral hypoglycemic agents (sulfonylureas or a combination of sulfonylureas and metformin), we studied whether administration of sulfonylureas immediately before breakfast had any effect on postprandial C-peptide values. Absolute differences between two consecutive fasting C-peptide concentrations in insulin-requiring patients were less than 0.1 nM in all but 1 patient, in whom the difference was 0.18 nM. In subjects treated with oral hypoglycemic agents the median difference was 0.12 nM (range 0-0.38 nM). Absolute differences between two consecutive postprandial C-peptide concentrations were all less than 0.1 nM in insulin-requiring patients. No significant difference was found between postprandial C-peptide concentrations with or without preceding administration of oral hypoglycemic agents (medians 1.35 and 1.30 nM, respectively). Glucagon-stimulated C-peptide concentrations were somewhat higher than the postprandial values. However, equal discrimination between insulin-requiring and non-insulin-requiring diabetic patients was found by measuring postprandial or glucagon-stimulated C-peptide concentrations.