Lyme disease: clinical features, classification, and epidemiology in the upper midwest

Lyme disease can be classified using the terminology of syphilis. In this series of 95 cases from the upper midwest, early cases, defined as an illness of less than 2 months, were more likely to have lived in or recently visited a highly endemic area. Unlike late cases, early cases presented entirely in the nonwinter months (p less than .001). Early disease was further subdivided into primary and secondary disease. Ninety percent of primary and 43% of secondary cases had erythema migrans, while no late cases had active erythema migrans (p less than .001). Clinical manifestations of nonspecific inflammation, except for arthralgia, were more common in early than late disease (p less than .01). In secondary cases, monoarticular arthritis was slightly more common than polyarticular arthritis, with the reverse occurring in late disease (p less than .05). Indirect fluorescent antibody testing revealed a ratio of IgM to IgG antibodies to be helpful in distinguishing early from late disease. Antibacterial therapy in early, primary cases caused Jarisch-Herxheimer reaction 7% of the time. Despite longer and more frequent parenteral therapy, late Lyme disease frequently required retreatment, owing to poor clinical response (p less than .05).     

Action of diltiazem on excitation-contraction coupling in bullfrog skeletal muscle fibers

In this study the calcium antagonist drug diltiazem was found to produce twitch potentiation, lower the mechanical threshold potential and block inward calcium currents in bullfrog skeletal muscle fibers. Under tonic conditions (stimulation either every 1 or 2 min) high concentrations of diltiazem were required to enhance twitch tension (ED50 = 249 microM) and block calcium currents (IC50 = 190 microM). In addition, 100 microM diltiazem lowered the mechanical threshold rheobase potential from -49.3 to -57.0 mV. At higher rates of stimulation, concentrations of diltiazem as low as 1 and 10 microM, which had no tonic action, were found to produce twitch potentiation and calcium channel block, respectively. Onset and washout of tonic and frequency-dependent actions of diltiazem on twitch and current amplitude occurred over a similar time course. It is proposed that the mechanical potentiation, as well as the calcium channel block produced by diltiazem, result from the interaction of diltiazem with the same or similar receptor site(s).     

Autosomal dominant polycystic kidney disease: symptoms and clinical findings

In 259 subjects at risk to have inherited autosomal dominant polycystic kidney disease (PKD), the frequency of symptoms consistent with urinary tract infection, haematuria, back and abdominal pain, hypertension, renal stones, and end-stage renal failure was evaluated. The diagnosis of PKD was made in 140 of these subjects (54 per cent). At the time of the study, 36 per cent of males and 7 per cent of females with PKD were asymptomatic, normotensive, and denied any previous problems. In patients younger than 30 years, 66 per cent of males but only 11 per cent of females were asymptomatic. In female patients, urinary tract infection (69 per cent) and hypertension (61 per cent) were the most frequent clinical manifestations. In contrast, in males with PKD, these problems were present in only 19 per cent and 42 per cent, respectively. Frequency of other clinical manifestations was similar in women and men with PKD. End-stage renal failure was present in 5 per cent of the 81 patients younger than age of 40, in 33 per cent of the 27 patients 40-49 years old, and in 47 per cent of the 32 patients aged 50 years or more. Physical examination was unreliable in estimating kidney size in most patients, particularly in early stages of the disease. Hypertension and symptoms such as haematuria and back pain, but not urinary tract infections, correlated well with renal size measured by radiograms.     

HIV malingering in the accident and emergency department.

This paper reports a number of cases of patients attending an accident and emergency (A&E) department claiming to be HIV positive when they have been tested negative and are known to be negative by other departments in the hospital. The reasons for these patients claims are not always apparent. These patients may place an inappropriate workload on an already busy department. We caution doctors working in A&E departments to be vigilant when dealing with patients who claim to be HIV positive when there are no clinical or laboratory findings to substantiate the claim and we recommend liaison between relevant departments within a hospital and the patient's general practitioner (GP) when dealing with these patients.     

Comparison of hematopoietic progenitor cells in human umbilical cord blood collected from neonatal infants who are small and appropriate for gestational age

BACKGROUND: Cord blood has been used for transplantation. The purpose of this study was to compare numbers of hematopoietic progenitors in cord blood collected from neonatal infants who are small for their gestational age and those who are normal. STUDY DESIGN AND METHODS: Sixteen pregnant women diagnosed with intrauterine growth restriction were prospectively identified. Cord blood was collected at delivery. Fourteen cord blood samples were obtained from gestational age-matched, appropriately grown newborns. In vitro assays for hematopoietic progenitors were performed and results of the two compared. Comparisons were also made with numbers of hematopoietic progenitor cells previously found by this laboratory in samples collected with the possibility of use for transplantation. RESULTS: Gestational age, the women's pregnancy and delivery histories, maternal risk factors for intrauterine growth restriction, maternal age, delivery method, umbilical cord blood gases, and 5-minute Apgar scores were similar in the two groups. Newborns who were small for their gestational age had significantly lower birth weights and longer stays in the neonatal intensive care unit with no evidence for viral infections in the immediate neonatal period. The mean number of progenitors per collection of cord blood in the small newborns was about half that per collection from appropriately grown newborns, but in most cases, these differences were not significant in the two groups, and many numbers in the small newborns fell within the range associated with successfully engrafting cord blood collections. CONCLUSION: Hematopoietic progenitor cells in the small newborns may be adequate for transplantation purposes in many cases. Their possible use in this context should, however, involve careful consideration of the numbers of progenitors collected as well as of possible viral or other contamination.     

Timely diagnosis and management of heparin‐induced thrombocytopenia in a frequent request,low incidence single centre using clinical 4T’s score and particle gel immunoassay

Clinicians must promptly decide which patients suspected of having heparin‐induced thrombocytopenia (HIT) warrant a change in anticoagulation. This single‐centre series of 246 HIT testing referrals assessed the combination of clinical score (thrombocytopenia, timing, thrombosis, other causes of thrombocytopenia not evident; 4T’s), Diamed ID‐Heparin‐PF4 immunoassay (PaGIA) and 14C Serotonin Release Assay (SRA) to develop a practical and safe diagnostic strategy for HIT. A total of 142/256 (58%) referrals were in patients with a low 4T’s score, with 12/246 (5%) in the high scoring group. PaGIA was positive in 24/246 (9·7%) patients, whilst SRA was positive in 9/246 (3·6%). The overall positive predictive value of a positive PaGIA test alone was 37·5%, however this reached 80% for the high scoring group. Both negative PaGIA and low clinical score independently had negative predictive values of 100%. We subsequently developed an algorithm that, when applied to this cohort, would have resulted in 18/246 patients (7%) definitely requiring alternative anticoagulation, whilst a further 7/246 (2·8%) patients would have been considered on an individual basis. Ultimately (based on SRA) this would have resulted in 16/246 (6·5%) patients unnecessarily having a change in their anticoagulation, with 9/246 (3·6%) patients being ‘correctly treated’. The combination of 4T’s scoring and PaGIA permitted a practical and safe approach to rapid HIT diagnosis and management.     

Ex vivo resuscitation of adult pig hearts

One possible way to expand the human heart donor pool is to include non-heart-beating human donors. To begin validating this approach, we developed an ex vivo cardiac perfusion circuit to support large mammalian hearts in Langendorff mode and beating-ejecting mode and to assess and improve their ischemic tolerance. In vivo hemodynamic data and heparinized blood (4.0 +/- 0.5 L) were collected from 6 anesthetized pigs. Hearts were isolated and connected to a recirculating perfusion circuit primed with autologous buffered blood (pH, 7.40). After retrograde aortic perfusion in Langendorff mode, the left atrium was gravity-filled at 10-20 mmHg, and the left ventricle began to eject against a compliance chamber in series with a systemic reservoir set to a hydraulic afterload of 100-120 mmHg. Left ventricular function was restored and maintained in all 6 hearts for 30 min. Cardiac output, myocardial oxygen consumption, stroke work, aortic pressure, left atrial pressure, and heart rate were measured. The mean myocardial oxygen consumption was 4.8 +/- 2.7 mL/min/100 g (95.8% of in vivo value); and mean stroke work, 5.3 +/- 1.1 g x m/100 g (58.95% of in vivo value). One resuscitated heart was exposed to 30 min of normothermic ischemic arrest, then flushed with Celsior and re-resuscitated. The ex vivo perfusion method described herein restored left ventricular ejection function and allowed assessment of ischemic tolerance in large mammalian hearts, potentially a 1st step toward including non-heart-beating human donors in the human donor pool.     

Increased membrane permeability to chloride in Duchenne muscular dystrophy fibroblasts and its relationship to muscle function.

Previous studies have suggested an abnormality in Cl- metabolism in Duchenne muscular dystrophy (DMD) fibroblasts. In order to further characterize this abnormality, we have studied 36Cl- distribution and permeability in 11 DMD and 12 normal fibroblast lines. Under steady-state conditions Cl- efflux in fibroblasts is observed to be biphasic, revealing the presence of two major subcellular compartments. Each compartment contains approximately half of the cellular Cl-. The faster of the two observed efflux components is significantly higher in DMD than in control fibroblasts (P less than 0.001). To determine the results of a similar increase in Cl- permeability on skeletal muscle action potentials, we have simulated the effects of increased Cl- conductance on muscle by using a computer model. Effects on the simulated action potential include lower rates of membrane depolarization, lower overpotential, longer duration, and lower input resistance. These effects are similar to those actually observed in DMD muscle.     

Incorporation of 12-methoxydodecanoate into the human immunodeficiency virus 1 gag polyprotein precursor inhibits its proteolytic processing and virus production in a chronically infected human lymphoid cell line.

Covalent linkage of myristate (tetradecanoate; 14:0) to the NH2-terminal glycine residue of the human immunodeficiency virus 1 (HIV-1) 55-kDa gag polyprotein precursor (Pr55gag) is necessary for its proteolytic processing and viral assembly. We have shown recently that several analogs of myristate in which a methylene group is replaced by a single oxygen or sulfur atom are substrates for Saccharomyces cerevisiae and mammalian myristoyl-CoA:protein N-myristoyltransferase (EC 2.3.1.97; NMT) despite their reduced hydrophobicity. Some inhibit HIV-1 replication in acutely infected CD4+H9 cells without accompanying cellular toxicity. To examine the mechanism of their antiviral effects, we performed labeling studies with two analogs, 12-methoxydodecanoate (13-oxamyristate; 13-OxaMyr) and 5-octyloxypentanoate (6-oxamyristate; 6-OxaMyr), the former being much more effective than the latter in blocking virus production. [3H]Myristate and [3H]13-OxaMyr were incorporated into Pr55gag with comparable efficiency when it was coexpressed with S. cerevisiae NMT in Escherichia coli. [3H]6-OxaMyr was not incorporated, even though its substrate properties in vitro were similar to those of 13-OxaMyr and myristate. [3H]13-OxaMyr, but not [3H]6-OxaMyr, was also efficiently incorporated into HIV-1 Pr55gag and nef (negative factor) in chronically infected H9 cells. Analog incorporation produced a redistribution of Pr55gag from membrane to cytosolic fractions and markedly decreased its proteolytic processing by viral protease. 13-OxaMyr and 3'-azido-3'-deoxythymidine (AZT) act synergistically to reduce virus production in acutely infected H9 cells. Unlike AZT, the analog is able to inhibit virus production (up to 70%) in chronically infected H9 cells. Moreover, the inhibitory effect lasts 6-8 days. These results suggest that (i) its mechanism of action is distinct from that of AZT and involves a late step in virus assembly; (ii) the analog may allow reduction in the dose of AZT required to affect viral replication; and (iii) combinations of analog and HIV-1 protease inhibitors may have synergistic effects on the processing of Pr55gag.     

Do Alcohol Misuse,Smoking, and Depression Vary Concordantly or Sequentially? A Longitudinal Study of HIV-Infected and Matched Uninfected Veterans in Care

We analyzed temporal patterns of alcohol misuse, smoking, and depression among veterans in care to determine whether these conditions vary concordantly or sequentially. Using the Veterans Aging Cohort Study, harmful alcohol use (AUDIT-C ≥ 4), current smoking, and depression (PHQ-9 ≥ 8), were measured. In regression analyses, predictors included each outcome condition at baseline, the other two conditions in the same survey, the other two conditions in the immediately preceding survey, number of years since enrollment, and HIV status. We found that current smoking and depression were more common among HIV infected individuals. Harmful alcohol use was more common among uninfected individuals. Temporal analyses suggested a concurrent pattern: each condition was associated with the other two conditions (p < 0.03, OR 1.12–1.66) as well as with the prior presence of the same condition (p < 0.0001; OR 6.38?22.02). Smoking was associated with prior depression after controlling for current depression (OR 1.16; p = 0.003). In conclusion, alcohol misuse, smoking, and depression were temporally concordant and persistent, raising the question of whether they constitute a common syndrome in HIV infected patients and others with chronic diseases.