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Biomedical subjects

S A Spector

Publications and source records attributed to S A Spector.

At least 181 records · Page 10Linked to original sources
PubMed1982

Effects of acyclovir combined with other antiviral agents on human cytomegalovirus.

At present, there is no effective therapy for human cytomegalovirus (CMV) infections. Although acyclovir inhibits in vitro clinical isolates of CMV, preliminary human trials suggest that acyclovir may not be successful as a single antiviral agent in treating CMV infections. The antiCMV activity of acyclovir in combination with human fibroblast interferon (IFN-beta), phosphonoformic acid (PFA), or trifluorothymidine (TFT) was therefore evaluated. When acyclovir (20 microM) was combined with IFN-beta (25 U/ml), additive antiviral effects were observed for the four clinical CMV isolates studied and the laboratory adapted strain, AD-169. The combination of acyclovir (20 microM) with PFA (25 microM) was synergistic for all four clinical isolates studied, but additive for the AD-169 strain. Similarly, the combination of acyclovir (20 microM) and TFT (0.17 microM) was synergistic for three of four clinical isolates, and additive for one clinical strain and the AD-169 virus. These findings suggest that acyclovir combined with other antiviral agents may be useful in the treatment of CMV disease.

Acyclovir↗
PubMed1982

Neonatal acyclovir pharmacokinetics in patients with herpes virus infections.

A preliminary analysis is presented of the pharmacokinetics of acyclovir in neonatal patients with herpes simplex virus infections. Mean peak acyclovir levels (microM +/- SD) at 5, 10, and 15 mg/kg per dose were 30.0 +/- 9.9, 61.2 +/- 18.3, and 86.1 +/- 23.5, with corresponding mean trough levels (microM +/- SD) of 5.3 +/- 3.4, 10.1 +/- 8.4, and 13.8 +/- 11.1, respectively. The mean half-life (t 1/2 beta) of acyclovir was 3.78 +/- 1.21 hours. The mean percent urinary recovery of acyclovir (+/- SD) at each dosage level was similar, with an overall mean recovery of 65 percent. The mean acyclovir concentration in urine did not exceed the solubility of acyclovir in bladder urine (1,300 micrograms/ml). Generally, neonatal acyclovir pharmacokinetics was consistent with previous reports from studies of adults.

Acyclovir↗
PubMed1982

Treatment of herpes virus infections in immunocompromised patients with acyclovir by continuous intravenous infusion.

Sixteen immunocompromised patients with herpes virus infections were treated for three to five days with continuously administered intravenous acyclovir. Patients received initial acyclovir infusions over 5 minutes in dosages ranging from 1.5 to 5.0 mg/kg followed by continuously infused acyclovir at 7.2, 14.4, 21.6, 28.8, 36.0, or 43.2 mg/kg per day. The mean serum plateau levels of acyclovir determined by radioimmunoassay ranged from 4.1 microM for the 7.2 mg/kg per day dosage to 36.6 microM for the 43.2 mg/kg per day dose. A mean of 75 percent of acyclovir administered was recovered in the urine of patients treated. Eleven of 13 patients with varicella-zoster virus (VZV) infections had no new vesicle formation after three days of acyclovir treatment and all patients ceased to have new vesicles after five days of therapy. For the nine patients from whom complete viral cultures were available, six ceased to shed virus at three days, and viral shedding ceased by five days in all patients treated with acyclovir. No clinical or laboratory adverse reactions were associated with acyclovir therapy. These data suggest that acyclovir given by continuous intravenous infusion may be useful in the treatment of herpes virus infections in immunocompromised patients.

Acyclovir↗
PubMed1982

Histochemical and physiological properties of cat motor units after self-and cross-reinnervation.

1. This report describes selected histochemical and physiological properties of the motor units of adult cat soleus muscle approximately one year after self- and cross-reinnervation with the nerve of the heterogenous flexor hallucis longus (f.h.l.). Self-reinnervated f.h.l. motor units are also considered. Whole muscles were tested for fibre reaction to alkaline pre-incubated ATPase, alpha-glycerophosphate dehydrogenase (alpha-GPD) and reduced nicotinamide adenine dinucleotide diaphorase (NADH-D). Motor units were isolated and studied by splitting the ventral root in acute preparations.2. The histochemical fibre type profile in the self-reinnervated muscle was comparable to normal muscle as was mean twitch contraction time, twitch-tetanus ratio and fatigue index. The mean tetanic tension of the soleus self- and cross-reinnervated motor units appeared close to a normal soleus whereas the mean tetanic tension of the f.h.l. self-reinnervated units was significantly less than a normal f.h.l.3. An average of 14% of the fibres of the soleus cross-reinnervated muscles had high ATPase and a alpha-GPD staining intensity in contrast to normal and self-reinnervated soleus in which such fibres are absent. Thus alkaline lability of myofibrillar ATPase increased in some fibres of what was originally a homogeneous population. The small increase in the number of densely staining fibres for ATPase at an alkaline pH (14%) was associated with a 73% decrease in (mean) contraction time (41 +/- 11 ms) of the thirty-three cross-reinnervated muscle units studied, with no unit's contraction time greater than 60 ms. Mean contraction times for the self-reinnervated soleus and f.h.l. muscles were 78 +/- 31 ms and 27 +/- 8 ms respectively.4. All fibres of the soleus cross-reinnervated muscles showed intense reaction to NADH-D, as was true of self-reinnervated soleus. This staining pattern is typical of normal soleus. In concordance, these motor units consistently demonstrated a high resistance to fatigue when stimulated for a four-minute period.5. These results suggest that in the adult self-and cross-reinnervated soleus muscle, there is some active mechanism which regulates the eventual size of motor units as reflected by tetanic tension.6. Change in contraction time from that typical for a soleus unit to that similar to an f.h.l. unit remains incomplete one year after cross-reinnervation. Within this time this partial change in single motor units reflects incomplete neural control of this property rather than a mixture of self- and foreign-innervation.7. A greater degree of independence from neural control to conversion of the histochemically demonstrated myofibrillar ATPase activity exists than is the case for contraction time.

Animals↗
PubMed1981

Fatal echovirus type 11 infections.

Two infants with fatal echovirus type 11 infections are described. Disseminated intravascular coagulation developed in both patients, and at postmortem examination, diffuse hemorrhagic necrosis of multiple organ systems was evident, most strikingly in the liver. A 3-month-old child is described, in whom lethargy, vomiting, pitting edema of the occipital scalp and neck, and subsequent diffuse echovirus disease developed. The clinical manifestation in this infant of focal myositis with histologic documentation at postmortem examination is unique to echovirus 11 disease. To our knowledge, this child represents the first described patient with nonparalytic, fatal echovirus type 11 infection occurring beyond the immediate neonatal period.

Disseminated Intravascular Coagulation↗
PubMed1981

Single-dose pharmacokinetics of acyclovir.

The pharmacokinetics of intravenously administered acyclovir were studied in 10 patients with advanced malignancies. After doses of 0.5 and 1.0 mg/kg, the slow disposition half-life values (t1/2beta) ranged from 2.2 to 3.1 h for the 1-h infusions and from 1.8 to 3.7 h for the 6-h infusions. Plasma levels, measured by radioimmunoassay, reached a maximum at the end of the 1-h infusions and approached steady state at 3 to 4 h into the 6-h infusions. Mean peak plasma concentrations obtained at 0.5 and 1.0 mg/kg administered over 1 h were 3.03 and 5.99 microM, respectively. Mean peak levels for the 6-h infusions were 1.07 microM at 0.5 mg/kg and 2.58 microM at 1.0 mg/kg. The mean urinary elimination of acyclovir was 44.7% of the administered doses. No clinical or laboratory abnormalities were noted in the 10 patients studied.

Acyclovir↗
PubMed1980

Is resistance of a muscle to fatigue controlled by its motoneurones?

The original experiment of Buller et al. and the many subsequent confirmatory reports clearly show that the time-to-peak tension and many other speed-related parameters of slow and fast muscle fibres are dictated by the motoneurone. It has been concluded that the motoneurone exerts this control of the physiological and associated biochemical properties by the frequency at which it excites the muscle fibre. However, no studies have been reported on the fatigue properties and the associated biochemical characteristics after cross-reinnervation. Based on the 'size principle' of motoneurones, it would be reasonable to assume that a muscle fibre reinnervated by a small motoneurone would be active often and that this would be manifested biochemically as an elevated oxidative capacity. Also, it has been shown repeatedly that the mitochondrial content of a muscle fibre can be modified by daily endurance type exercise. Thus, it would seem that the motoneurone at least indirectly also controls the mitochondrial content of a muscle fibre by controlling the degree of activity. We have now tested this hypothesis using self- and cross-reinnervated muscles in cats. We found that fast- and slow-twitch muscles retained their characteristic fatigue resistance properties regardless of whether the nerve to which they had become connected had originally innervated a fatigue-resistant or relatively fatiguable muscle.

Adenosine Triphosphatases↗
PubMed1980

Muscle architecture and force-velocity characteristics of cat soleus and medial gastrocnemius: implications for motor control.

1. Isometric and isotonic contractile parameters of the soleus (SOL) and medial gastrocnemius (MG) muscles of seven adult cats were studied. In addition, architectural characteristics of six contralateral pairs of these ankle extensors were determined. 2. The in situ peak isometric tetanic tension developed by the MG at the Achilles tendon is nearly 5 times (9,846 vs 2,125 g) that of the SOL muscle. However, when differences between the MG and SOL in fiber length (2.01 vs 3.66 cm), muscle mass (9.80 vs. 3.31 g), and angle of pinnation (21.4 vs. 6.4 degrees) are considered, the specific tensions of these muscles are similar (approximately 2.3 kg x cm-2). 3. When the effects of muscle architecture are eliminated, the nearly threefold greater maximum isotonic shortening velocity (Vmax) of sarcomeres of the MG (38.2 micron/s) relative to the SOL (13.4 micron/s) is presumably due to intrinsic differences in the biochemical properties of these muscle. However, the Vmax developed by the MG at the Achilles tendon (258.6 mm/s) during a shortening contraction is only 1.5 times that of the SOL (176.3 mm/s) due to the influence of these muscles' specific architectures. 4. Variations in geometrical characteristics of the SOL and MG are consonant with the relative amounts of participation of these muscles during posture, locomotion, and jumping. Posture requires the development of low forces for prolonged periods for which the SOL seems best suited both architecturally and physiologically. The MG, relatively inactive during quiet standing, becomes responsible for a greater percentage of tension and shortening speed during plantar flexion (E3) as gait speeds increase, which is consistent with this muscle's greater tension- and velocity-generating capacity. 5. At high speeds of locomotion (3.0 m/s) and jumping, the shortening velocities developed at the end of E3 (approximately 20-40 ms before paw off) exceed Vmax of the SOL. Consequently, the SOL, although electrically active, cannot contribute to the tensions required to generate the shortening velocities dictated by these movements. 6. These data demonstrate the influence of the differing geometries of the SOL and MG on the roles of these muscles in generating forces at varying velocities, as demanded by the dynamics of the movement.

Animals↗
PubMed1979

Cytomegaloviruria in older infants in intensive care nurseries.

Over a four-month period, urine specimens for viral isolation were obtained weekly from all infants older than three weeks in two intensive care nurseries. These babies comprised 43% of the patients in the nurseries surveyed. Cytomegalovirus was cultured from 13 of 93 (14%) of these infants. Eleven of 13 infants who developed cytomegaloviruria were born prematurely, and nine of these 11 were found to be excreting CMV before they reached 40 weeks postconception. Infants excreting CMV received blood transfusions from a mean of 10.45 (+/- 1.80 SE) different donors versus 5.10 (+/- 0.55 SE) for infants without viruria (P less than 0.002) and five of 14 infants undergoing one or more exchange transfusions developed cytomegaloviruria (P less than 0.05). The possible role of other CMV reservoirs and the importance of these findings are discussed.

Cross Infection↗
PubMedDate not supplied

Applications of immunogold-silver enhancement: testing of monoclonal antibodies and detection of human cytomegalovirus in histologic specimens.

Human cytomegalovirus (HCMV) is an important pathogen in neonates, transplant patients, and individuals with acquired immunodeficiency syndrome (AIDS). Reliable techniques for the detection of this virus in clinical specimens would aid in improving methods for diagnosis and increasing our understanding of viral pathogenesis. We evaluated the utility of immunogold-silver enhancement to determine the specificity of murine monoclonal antibodies directed against HCMV proteins and applied these antibodies to the detection of HCMV in histologic material. Nine antibodies were tested in a tissue-culture system to determine the location of staining. All were found to be active in frozen tissue, but only two of these antibodies were reactive in formalin-fixed tissue. We also evaluated a novel tissue fixative technique (AMeX; Fixation and dehydration with acetone) that has been used to maintain antigenicity of T-lymphocyte cell markers. All antibodies remained reactive against their respective HCMV proteins in tissue fixed by this technique. However, dehydration of tissue may limit the usefulness of AMeX fixation. Immunogold-silver enhancement is a useful and reliable histochemical technique for detection of HCMV antigens in pathologic specimens.

Antibodies, Monoclonal↗
PubMedDate not supplied

Malassezia fungemia in neonates and adults: complication of hyperalimentation.

Until recently, Malassezia furfur was thought to be a pathogen only in tinea versicolor. More recently, this lipophilic yeast has been recovered from sick neonates with catheter-related infections. Malassezia fungemia was studied in seven patients, and the salient features of this infection in patients described in the literature were reviewed. Major risk factors include prolonged hospitalization, the presence of central venous catheters, and the use of intravenous fat emulsions. It is difficult to identify specific manifestations of fungemia in these complex cases occurring in patients with severe underlying disease; however, neonates often present with the signs and symptoms of sepsis and thrombocytopenia, whereas fever may be the only manifestation in adults. Some patients are asymptomatic. When symptoms are present, they resolve upon removal of the colonized catheter. The role of the lipophilic nature of Malassezia in the pathogenesis of infection is apparent from the ability of intravenous fat emulsions to support the growth of the fungus in vitro. A special solid medium that can be used to determine the true prevalence of malassezia fungemia has been devised. M. furfur must be considered in the differential diagnosis of opportunistic infections in patients receiving central hyperalimentation and should be sought by the culture of blood on appropriate medium.

Agar↗
PubMedDate not supplied

Molecular epidemiology of cytomegalovirus infections in premature twin infants and their mother.

Premature identical twins are described who according to molecular fingerprinting of their viral isolates, demonstrate a nonmaternal nursery source for their acquired cytomegalovirus (CMV) infections. The babies were born via cesarean section at 29 weeks gestation. Weekly urine screening of the infants indicated that at birth both were CMV-negative. Twin B developed CMV at 6 weeks of age, while Twin A developed his infection when he was 9 weeks old. Three months following delivery cervical and urine cultures of the infants' mother were negative and she had no detectable CMV antibody. At 6 months postpartum (2 months following both infants' discharge home) a repeat urine culture of their mother was positive for CMV, and here CMV-CF titer had risen to 1:128. DNA fingerprinting by restriction endonuclease digestion analyses of the viruses isolated from the two infants indicate that they were infected with different strains of CMV. In addition the DNA fingerprinting pattern of the mother's isolate is identical to that of Twin A. These cases give further evidence that hospitalized infants may acquire CMV from hospital sources and document by molecular fingerprinting for the first time to our knowledge that these babies may transmit the virus to CMV-seronegative individuals. This study also demonstrates how restriction endonuclease digestion analyses can be used as a powerful tool to study the epidemiology of CMV infections.

Adult↗