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Biomedical subjects

R E Miller

Publications and source records attributed to R E Miller.

At least 91 records · Page 5Linked to original sources

Surgical laparoscopic experience during the first year on a teaching service.

Recently, general surgeons have become actively involved in laparoscopic operations. The best method for teaching these techniques to surgical residents is unclear. Since June 1990, at St. Luke's-Roosevelt Hospital Center in New York City, we have instituted a formal course of instruction for surgical residents. This includes a reference syllabus, didactic instruction, use of an inanimate training device and a hands-on practice in swine. Clinically, the residents progress from observer to camera operator and, finally, operator. During the first year of this program, the authors performed 90 laparoscopic cholecystectomies, of which 71 were elective and 19 were for acute cholecystitis. There were seven morbidly obese patients, while 25 had undergone prior abdominal operations. The first 25 operations performed by the authors averaged 93.2 minutes, while the last 40 operations performed primarily by the surgical residents with assistance of the authors averaged 70 minutes. There were nine complications, including postoperative pancreatitis in two patients, Clostridium difficile enterocolitis in two and one each of prolonged paralytic ileus, postoperative transfusion and umbilical incision dehiscence. Two patients had postoperative common duct stones. There were no wound infections, bile duct injuries or deaths. Complications were evenly distributed throughout the series and did not correlate with whether the surgeon was a resident or an attending surgeon. The results of this plan have been quite successful and thus far, 12 residents have completed this program.

Cholecystectomy, Laparoscopic↗

Prescribing spectacles for aviators: USAF experience.

This special report was written for USAF vision specialists to use as a guide when prescribing spectacles for military aviators and to extend to the civilian sector the knowledge gained from the USAF experience. Visual correction in aviators presents some unique problems, especially for presbyopes. The demands of each individual aircraft environment need to be well understood. Ophthalmologists and optometrists must consider all pertinent aeromedical factors before prescribing spectacles for ametropic aviators.

Adult↗

Contact lens wear with the USAF Protective Integrated Hood/Mask chemical defense ensemble.

The Protective Integrated Hood/Mask (PIHM) chemical defense aircrew ensemble blows air from the mask's plenum across the visor at a rate of approximately 15 L/min in order to prevent fogging of the visor and to cool the aircrew member's face. This study was designed to determine the effect of the PIHM airflow on soft contact lens (SCL) dehydration, contact lens comfort, and corneal integrity. There were 26 subjects who participated in this study: 15 SCL wearers, 6 rigid gas-permeable (RGP) wearers, and 5 nonspectacle wearing controls. Contrast acuity with the 3 Regan charts, subjective comfort, and relative humidity (RH) and temperature readings under the PIHM mask were monitored every 0.5 h during 6-h laboratory rides. Slit-lamp examinations and SCL water content measurements with a hand-held Abbe refractometer were made before and after the rides. High RH under the mask may have accounted for the moderate SCL dehydration (8.3%), no decrease in contrast acuity for any group, and lack of corneal stress. Although all groups experienced some inferior, epithelial, punctate keratopathy, RGP wearers had the most significant. SCLs performed relatively well in the PIHM mask environment. Testing with other parameter designs is necessary before recommending RGPs with the PIHM system.

Aerospace Medicine↗

A functional promoter flanks an intronless glutamine synthetase gene.

We recently reported the 5'-flanking nucleotide sequence of a putative glutamine synthetase (GS) gene from 3T3-L1 cells (Bhandari, B., Beckwith, K. D. & Miller, R. E. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 5789-5793). We now find that this gene (GSr) has many, but not all, of the characteristics of a typical retroposon. It lacks introns, it contains a short poly(A) tract at its 3' end; it is flanked by 10-base pair (bp) direct repeats; and it corresponds closely at its 5' end to the transcription start site of the intron-containing GS gene (GSi) (Kuo, C. F. & Darnell, J. E., Jr. (1989) J. Mol. Biol. 208, 45-56). GSr includes a full-length, uninterrupted coding sequence that differs little (less than 5%) from that of the intron-containing gene. By contrast, the 5'-flanking sequence of GSr has no similarity with that of GSi. The first 1,029 bp of the GSr 5'-flanking sequence drives expression of a promoterless bacterial chloramphenical acetyltransferase (CAT) gene in transfected HeLa cells at a level comparable to that of the Rous sarcoma virus promoter. Analysis of variably deleted GSrCAT fusions genes in both HeLa and 3T3-L1 cells indicates that full promoter activity of the 1,029-bp sequence requires greater than 348 bp. Moreover, nuclear extract from 3T3-L1 adipocytes as well as murine liver protects four segments in the GSr 5'-flanking sequence from DNase I digestion. Nevertheless, reverse transcription of RNA from 3T3-L1 adipocytes, mouse adipocytes, or mouse liver followed by primer-directed enzymatic amplification of the reverse transcripts reveals the presence of GSi transcripts but the absence of GSr transcripts. Thus, the 5'-flanking sequence of GSr is an active promoter that drives transcription of GSrCAT fusion genes and includes binding domains for proteins that have the potential to regulate transcription. We conclude that the intronless murine GS gene isolated from 3T3-L1 cells arose as a retroposon that was inserted into the genome downstream of a potentially active promoter.

Autoradiography↗

Persistent cutaneous ulcers associated with feline herpesvirus type 1 infection in a cheetah.

Persistent cutaneous ulcers developed in a female cheetah cub after an episode of rhinotracheitis. When they were 3 weeks old, the cub and a male littermate developed mucopurulent oculonasal discharge consistent with feline herpesvirus type 1 infection (feline viral rhinotracheitis). The male cub was weaned and its lesions resolved. The female cub remained with the dam until the cub was 3 months old, at which time plaque-like lesions developed on the eye margins and muzzle. These plaques regressed over the next month and were replaced with cutaneous ulcers ranging from 1 to 10 mm in diameter. Feline herpesvirus type 1 was isolated from biopsy specimens collected from the ulcers. Cutaneous ulcers are uncommon manifestations of feline herpesvirus infections and have not been reported in other exotic fields. A proposed susceptibility to viral infections related to low genetic diversity has been proposed in cheetahs, and may be involved in the pathogenesis of persistent herpetic ulcers.

Acinonyx↗

Immunotherapeutic elimination of syngeneic tumors in vivo by cytotoxic T lymphocytes generated in vitro from lymphocytes from the draining lymph nodes of tumor-bearing mice.

The draining lymph nodes (LN) of mice injected with viable syngeneic tumor cells contain populations of lymphoid cells which are capable of generating functional cytotoxic T lymphocytes (CTL) during an in vitro culture period without the need of secondary stimulation with irradiated tumor cells or addition of exogenous cytokines. Intravenous injection of as few as 2.5 x 10(6) tumor-reactive effector cells generated using this protocol effectively eliminated challenges of tumor cells at distal skin sites, whereas injection of cultured control lymphoid cells was ineffective at rejecting tumor challenges. The anti-tumor CTL generated from the draining LN of C57BL10 mice immunized with viable syngeneic tumor cells were found to be specific for the tumor used for immunization both in vitro and in vivo. Phenotypic analysis of the cells responsible for tumor elimination (both in vitro. and in vivo) demonstrated the anti-tumor effector cells to be CD4-CD8+ asialo GM1+NK1.1-. Finally, anti-tumor CTL generated during the short in vitro culture period were able to effectively reject pre-existing tumors in vivo in a systemic fashion. These data indicate that the generation of tumor-reactive CTL from the lymphoid cells contained in the LN draining the site of a tumor may provide a valuable source of effector cells which can be used in the immunotherapeutic treatment of cancer.

Animals↗

In vivo evaluation of the effects of interleukins 2, 4 and 7 on enhancing the immunotherapeutic efficacy of anti-tumor cytotoxic T lymphocytes.

The draining lymph nodes of mice injected with viable syngeneic tumor cells contain lymphoid cells capable of generating anti-tumor cytotoxic T lymphocytes (CTL) during a 4-day in vitro culture period and intravenous infusion of relatively low numbers of these CTL can effectively eliminate a challenge of fibrosarcoma cells at distal skin sites that would otherwise result in the death of the host. Using this model system the effects of addition of interleukin (IL) 2, IL4 or IL7 to the culture medium on the therapeutic efficacy of the anti-tumor CTL generated was investigated. In this regard, IL7 was found to be the most potent of the cytokines tested. Addition of IL7 either alone, or in combination with low doses of IL2, resulted in the generation of CTL with significantly (6-8-fold) enhanced therapeutic efficacy in vivo. Anti-tumor effector cells generated in the presence of IL7 were also found to be at least 4-fold more effective at eliminating established tumors than CTL generated in medium alone. Of the other cytokines tested, addition of IL2 resulted in elevated CTL activity in vitro, but only a modest (approximately 2-3-fold) enhancement of the therapeutic efficacy in vivo. Addition of IL4, either alone or in combination with IL2, also resulted in the generation of effector cells with enhanced tumoricidal activity in vitro and yet the therapeutic efficacy of these cells was decreased compared to that of CTL generated in medium alone. These observations indicate that (a) inclusion of IL7 in the medium in which tumor-reactive T cells are cultured can markedly enhance the immunotherapeutic efficacy of the resulting effector cell populations; and (b) in vitro assays of tumoricidal activity cannot be used as a reliable predictor of therapeutic efficacy in vivo.

Animals↗

Glycerol 3-phosphate dehydrogenase gene expression in cultured 3T3-L1 adipocytes: regulation by insulin, dexamethasone and dibutyryl cAMP at the level of mRNA abundance, transcription and mRNA stability.

In fully differentiated 3T3-L1 adipocytes, glycerol 3-phosphate dehydrogenase (G3PDH:Sn-glycerol 3-phosphate:NAD+ 2-oxidoreductase, EC 1.1.1.8) is subject to regulation by hormones and dibutyryl cAMP. An increase by insulin (4-fold) and decrease by dexamethasone (by 50%) and dibutyryl cAMP (by 70%) was observed for G3PDH mRNA abundance as analyzed by Northern blot hybridization. In addition, incubation of adipocytes with dibutyryl cAMP resulted in 3-fold increase in G3PDH gene transcription as measured by nuclear transcript elongation assay. The effects of these modulators on the control of G3PDH mRNA stability were also investigated. The G3PDH mRNA has a half-life of about 125 min. Dibutyryl cAMP caused an increase in G3PDH mRNA degradation by greater than 2-fold (t1/2 = 55 min) whereas insulin had an opposite effect (t1/2 = 240 min) and dexamethasone was without any effect on G3PDH mRNA stability. Taken together, our results directly demonstrate that in fully differentiated 3T3-L1 adipocytes the regulation of G3PDH gene expression by dibutyryl cAMP and insulin is exerted by alterations in transcription as well as mRNA stability.

3T3 Cells↗

Total parenteral nutrition in a premature rhinoceros calf.

A female black rhinoceros calf developed significant hypoglycemia (blood glucose, 30 mg/dL) and hypothermia (97 degrees F) within 48 hours of birth and refused to nurse. Normal gestation of the black rhinoceros is 15 months, but elongated hoof slippers and low birth weight (30 kg) suggested prematurity in this calf. Clinical symptoms of neonatal sepsis including lassitude and poor sucking continued in spite of the aggressive use of antibiotics, and the calf required mechanical ventilatory support on day 7. Nutritional support including enteral gavage feedings (Pedialyte/4 ounces of SMA [Wyeth Ayerst] with sucraflox) had been instituted and was supplemented with total parenteral nutrition on day 5. Central venous access was obtained via a jugular cutdown. The total parenteral nutrition included appropriate electrolytes and vitamins for the neonatal calf but did not include trace elements. The use of total parenteral nutrition by our zoos for therapeutic purposes is increasing. Experience with total parenteral nutrition in exotic animals such as the black rhinoceros is limited, yet this may be an important therapeutic modality in these animals, particularly those in danger of extinction.

Animals↗

Surgical management of complications of fiberoptic colonoscopy.

A variety of complications are associated with fiberoptic colonoscopy. Life-threatening complications such as perforation and hemorrhage may require surgical intervention. The records of all patients who underwent fiberoptic colonoscopy, with or without biopsy, polypectomy, electrocoagulation, or laser therapy at St. Luke's-Roosevelt Hospital Center were reviewed. Thirteen of 21 perforations occurred during polypectomy, laser therapy, or difficult diagnostic colonoscopy. Eight patients developed a perforation after an uneventful diagnostic colonoscopy. Three patients required operative control of hemorrhage following polypectomy and one after multipolar electrocoagulation (BICAP) therapy for a cecal arteriovenous malformation. Two patients had benign pneumoperitoneum and one a retained polyp snare. Of the 28 patients in this entire series, 26 underwent operative resection or repair. Seventeen (65%) of the latter group underwent primary resection or closure of perforation without protective fecal diversion. Only one (5.9%) septic complication occurred in this group. Twelve patients in the perforation group (57%) underwent primary resection with anastomosis or closure of perforation without fecal diversion. One (8.3%) developed a septic complication. In this entire series, four deaths (14.3%) occurred, all of which were in the perforation group. Delay in diagnosis of perforation was the main factor contributing to death. No patient died of hemorrhage, benign pneumoperitoneum, or retained polyp snare. The key to successful outcome in perforation is early diagnosis and prompt operative intervention.

Aged↗

Induction of murine lymphokine-activated killer cells by recombinant IL-7.

The data demonstrate that IL-7, a cytokine that was originally identified, purified, and cloned based upon its ability to support the growth of pre-B cells in vitro, also induces proliferation and promotes the generation of lymphokine-activated killer (LAK) cell activity in populations of resting peripheral lymphoid cells. Although the kinetics of LAK induction by IL-7 (which peaked at days 6 to 8 of culture) was slower than that detected in cultures containing IL-2 (which peaked at day 4), IL-7 was significantly more effective at maintaining cytotoxic activity over longer periods of time, and greater viable cell recoveries, than was IL-2. A wide range of murine tumor target cells were found to be lysed in an MHC-unrestricted fashion by IL-7 induced LAK, but syngeneic Con A-induced lymphoblasts were not; nor were target cells from the human tumors K562 or Daudi lysed by IL-7 LAK. IL-7 LAK were induced in populations of lymphoid cells obtained from secondary lymphoid tissues (peripheral lymph nodes and spleen), but not from primary lymphoid tissues (thymus and bone marrow). LAK induced by IL-7 from unfractionated populations of lymphoid cells were completely eliminated by treatment with anti-CD8 or anti-Thy-1+C, and unaffected by treatment with anti-CD4, anti-asialo GM1 or anti-NK1.1+C. Interestingly, although no detectable CD4+ effector cells could be detected in populations of LAK generated from unfractionated populations of lymphoid cells stimulated by IL-7, they were found to be generated from populations of lymphoid cells from which CD8+ cells had been eliminated before being cultured in medium containing IL-7. These data suggest that CD4+ T cells do not normally give rise to IL-7-induced LAK unless they are first separated from CD8+ T cells. LAK induced by IL-7 appear to be distinct from LAK activity induced by IL-2 in that there is no detectable involvement of NK-like effector cells at either the precursor or effector cell stages.

Animals↗

The roles of tyrosines 24, 31, and 60 in the high affinity binding of insulin-like growth factor-I to the type 1 insulin-like growth factor receptor.

A series of insulin-like growth factor I (IGF-I) structural analogs in which one or more of the three tyrosine residues were replaced with nonaromatic residues were produced and their binding properties characterized. The single point mutations, [Leu24]IGF-I, [Ala31]IGF-I, and [Leu60]IGF-I result in an 18-, 6-, or 20-fold loss in affinity, respectively, for the type 1 IGF receptor. Multiple mutations, [Ala31,Leu60]IGF-I, [Leu24, Ala31]IGF-I, [Leu24, Leu60]IGF-I, or [Leu24, Ala31, Leu60]IGF-I result in a 520-, 240-, 1200-, or greater than 1200-fold loss in affinity, respectively, at the type 1 IGF receptor. In contrast, none of the analogs display greater than a 2-fold loss in affinity for the acid-stable human serum binding proteins. At the insulin receptor, [Ala31]IGF-I and [Leu24]IGF-I are equipotent to and 5-fold less potent than IGF-I, whereas [Leu60]IGF-I and the multiple mutation analogs are inactive up to 10 microM. Analogs [Leu24]IGF-I, [Ala31]IGF-I, and [Leu24, Ala31]IGF-I are equipotent to IGF-I at the type 2 IGF receptor, whereas all analogs containing Leu60 demonstrate little measurable affinity at this receptor. Thus, Tyr24, Tyr31, and Tyr60 are involved in the high affinity binding of IGF-I to the type 1 IGF receptor, while Tyr60 is important for maintaining binding to the type 2 IGF receptor.

Amino Acid Sequence↗

Acute monensin toxicosis in Stone sheep (Ovis dalli stonei), blesbok (Damaliscus dorcus phillipsi), and a Bactrian camel (Camelus bactrianus).

Accidental monensin toxicosis developed in 5 Stone sheep (Ovis dalli stonei), 5 blesbok (Damaliscus dorcas phillipsi), and a Bactrian camel (Camelus bactrianus) at the St Louis Zoological Park. Eight animals died acutely and 1 was euthanatized because of chronic hind limb paresis. All affected animals had clinicopathologic evidence of severe muscle necrosis, serum electrolyte disturbances, and hemoconcentration.

Animal Feed↗

Hypertension: cognitive and behavioral considerations.

This article reviews literature concerning functional changes resulting from elevated blood pressure, from reduction of blood pressure, and as a result of the medications used to treat high blood pressure. The research reviewed includes the areas of psychomotor speed, intelligence and cognitive processing, sensory and perceptual processes, and emotional and interpersonal behaviors. The conclusions reached are that the deficits noted to date in hypertensive individuals are not extreme nor are they specific. The greatest disadvantage, however, appears in the area of response speed.

Antihypertensive Agents↗

Absence of behavioral differences in young normotensive adults as a function of parental history of hypertension.

It has been previously demonstrated that mildly hypertensive subjects show deficits in their performance on various sensory-perceptual, cognitive, and psychomotor tests relative to matched normotensive control subjects, and that these behavioral deficits are reversible following treatment with antihypertensive medication. To examine whether these deficits are an outcome of elevated blood pressure, rather than preceding the hypertensive state, normotensive offspring of hypertensives and normotensives were administered a test battery. Results showed that with minor exceptions, offspring of hypertensives and offspring of normotensives performed similarly on the tests. These results suggest that the behavioral deficits seen in hypertensives arise subsequent to the onset of elevated blood pressure.

Adolescent↗

Survey of spectacle wear and refractive error prevalence in USAF pilots and navigators.

A retrospective survey of 5000 active aircrew records was performed at 12 United States Air Force (USAF) bases to obtain information about the prevalence of spectacle wear and refractive error. The data revealed that 27.4% of pilots and 51.5% of navigators/weapons systems operators (Nav/WSO) required spectacles when flying. Of the spectacle-wearing pilots, 12.4% required bifocals. Myopia was the predominant refractive error and a relatively large percentage of aircrew members had astigmatism of 0.75 D or more, e.g., 33.1% of pilots. At the time of entry into the USAF, refractive error data were clustered around emmetropia with a definite skew toward hyperopia.

Adult↗

Rigid gas-permeable contact lens wear during + Gz acceleration.

This study was designed to determine how well rigid gas-permeable contact lenses maintain position on the cornea under high G forces, and the effect on visual acuity. One hyperopic and five myopic subjects were fitted with lenses made from Pasifocon C material (specific gravity = 1.07). Two lens diameters (8.8-9.4 mm and 9.6-10.0 mm) were compared upon the myopic subjects for centering on the cornea. Visual acuity was measured at + 1 Gz (baseline), +3 Gz, +4 Gz, +6 Gz, and +8 Gz in the straight-ahead, lateral, and up-gaze positions from three acuity charts mounted in the gondola. All lenses, as estimated from the videotape, decentered down the z axis 2-3 mm at high + Gz. Visual acuity was reduced at the higher +Gz levels to similar measurements in most subjects for both the contact lens and spectacle control rides. No lens displaced from the cornea or dislodged from the eye during any of the 25 centrifuge runs.

Aerospace Medicine↗