Postabsorptive carbohydrate adaptations to heat stress and monensin supplementation in lactating Holstein cows.

Multiparous cows (n=34, 89 d in milk, 537 kg) housed in environmental chambers were fed a control total mixed ration or one containing monensin (450 mg/cow per day) during 2 experimental periods (P): (1) thermal neutral (TN) conditions (constant 20°C) with ad libitum intake for 9 d, and (2) heat stress (HS, n=16) or pair-fed [PF; in TN (PFTN); n=18] for 9 d. Heat-stress was cyclical with temperatures ranging from 29.4 to 38.9°C. Rectal temperatures and respiration rates increased in HS compared with PFTN cows (38.4 to 40.4°C, 40 to 93 breaths/min). Heat stress reduced dry matter intake (DMI, 28%), and by design, PFTN cows had similar intakes. Monensin-fed cows consumed less DMI (1.59 kg/d) independent of environment. Milk yield decreased 29% (9.1 kg) in HS and 15% (4.5 kg) in PFTN cows, indicating that reduced DMI accounted for only 50% of the decreased milk yield during HS. Monensin had no effect on milk yield in either environment. Both HS and PFTN cows entered into calculated negative energy balance (-2.7 Mcal/d), and feeding monensin increased feed efficiency (7%) regardless of environment. The glucose response to an epinephrine (EPI) challenge increased (27%) during P2 for both HS and PFTN cows, whereas the nonesterified fatty acid response to the EPI challenge was larger (56%) during P2 in the PFTN compared with the HS cows. Compared with P1, whole-body glucose rate of appearance (Ra) decreased similarly during P2 in both HS and PFTN cows (646 vs. 514 mmol/h). Although having similar rates of glucose Ra, HS cows synthesized approximately 225 g less milk lactose; therefore, on a milk yield basis, glucose Ra decreased (3.3%) in PFTN but increased (5.6%) in HS cows. Regardless of environment, monensin-fed cows had increased (10%) glucose Ra per unit of DMI. From the results we suggest that the liver remains sensitive but adipose tissue becomes refractory to catabolic signals and that glucose Ra (presumably of hepatic origin) is preferentially utilized for processes other than milk synthesis during HS.

Alterations in expression of gluconeogenic genes during heat stress and exogenous bovine somatotropin administration.

Study objectives were to evaluate hepatic gluconeogenic enzyme gene expression in recombinant bovine somatotropin (rbST)-treated lactating dairy cattle during heat stress (HS) or in thermal-neutral, pair-fed (PF) animals. Twenty-two multiparous (99 d in milk, 656 kg of BW) Holstein cows were subjected to 3 consecutive experimental periods (7 d each): (1) thermal neutral, (2) HS or PF, and (3) HS or PF with rbST (Posilac, administered on d 1 of period 3). Liver biopsies were obtained on the final day of each period. Heat stress conditions progressively decreased dry matter intake for the first 5 to 6 d during period 2 before stabilizing (a decrease of 6.15 kg; 30%) on d 6 and 7, and feed intake remained stable and not different from period 2 during period 3. Cytosolic phosphoenolpyruvate carboxykinase mRNA abundance increased during PF, but was unaffected by HS or bST. Pyruvate carboxylase gene expression increased during HS and PF, and administering bST decreased pyruvate carboxylase mRNA abundance during both HS and PF. Insulin-like growth factor-I gene expression increased following bST administration during HS and PF, confirming hepatic bST responsiveness. Exposure to HS leads to a change in hepatic gluconeogenic enzyme profile that appears to be dependent on plane of nutrition.

Effects of heat stress on energetic metabolism in lactating Holstein cows.

Heat stress has an enormous economic impact on the global dairy industry, but the mechanisms by which hyperthermia negatively affect systemic physiology and milk synthesis are not clear. Study objectives were to evaluate production parameters and metabolic variables in lactating dairy cows during short-term heat stress or pair-fed conditions coupled with bST administration. Twenty-two multiparous Holstein cows were subjected to 3 experimental periods: 1) thermoneutral conditions with ad libitum intake for 7 d (P1); 2) heat stress (HS) with ad libitum intake (n=10) or pair-fed (PF) in thermoneutral conditions (n=12) for 7 d (P2), and 3) 7 d of HS or PF in conditions as described in P2 with recombinant bovine somatotropin administered on d 1 (P3). All cows received an intravenous glucose tolerance test (GTT) on d 5 of each period. Heat stress conditions were cyclical and temperatures ranged from 29.4 to 38.9 degrees C. Rectal temperatures and respiration rates increased during heat stress (38.6-40.4 degrees C and 44-89 breaths/min, respectively). Heat stress reduced dry matter intake by 30% and by design PF cows had similar intake reductions (28%). During heat stress and pair-feeding, milk yield decreased by 27.6% (9.6kg) and 13.9% (4.8kg), respectively, indicating that reduced feed intake accounted for only 50% of the decreased milk production. Milk yield increased with recombinant bovine somatotropin in both HS (9.7%) and PF (16.1%) cows. Cows in both groups were in positive energy balance (3.95 Mcal/d) during P1 but entered negative energy balance during P2 and P3 (-5.65 Mcal/d). Heat stress and pair-feeding treatments decreased (9.3%) basal glucose concentrations. Heat stress conditions had no effect on basal NEFA levels during P2; however, PF cows (despite a similar calculated energy balance) had a 2-fold increase in basal NEFA concentrations. Both groups had increased plasma urea nitrogen levels during P2 and P3 compared with P1. Basal insulin levels increased (37%) during P2 and P3 in HS cows but did not differ between periods in PF cows. During P2 and compared with P1, PF cows had a decreased rate of glucose disposal, whereas HS cows had a similar disposal rate following the GTT. During P2 and compared with P1, PF cows had a reduced insulin response whereas HS cows had a similar insulin response to the GTT. In summary, reduced nutrient intake accounted for only 50% of heat stress-induced decreases in milk yield, and feed intake-independent shifts in postabsorptive glucose and lipid homeostasis may contribute to the additional reduction in milk yield.

Evaluation of serotonin as a feedback inhibitor of lactation in the bovine.

Serotonin (5-HT), a neurotransmitter synthesized from tryptophan, has been proposed as a feedback inhibitor of lactation. We determined that the gene coding for tryptophan hydroxylase 1, the rate-limiting enzyme for 5-HT synthesis, is expressed in bovine mammary epithelial cells in vitro and is upregulated by prolactin. In addition, 5-HT reduced the expression of alpha-lactalbu-min and casein genes in vitro. Furthermore, inhibiting 5-HT synthesis with p-chlorophenylalanine or blocking the 5-HT receptor with methysergide (METH) increased milk protein gene expression. We then evaluated effects of intramammary 5-HT or METH infusion on production and milk composition in 6 multiparous Holstein cows. Cows were assigned to a repeated measures design of contralateral intramammary infusions of METH (20 mg/quarter per d) or saline for 3 d followed by a 7-d washout period before administering 5-HT (50 mg/quarter/d) or SAL for 3 d. For each udder half, milk yield was recorded twice and composition was determined once per day. Blood samples were harvested each day for plasma to determine glucose and nonesterified fatty acid concentrations. Evaporative heat loss, respiration rate, left and right udder temperatures, and rectal temperatures were obtained after each milking to evaluate possible systemic effects of infusions. During METH and saline infusions milk yield increased 10.9%. During 5-HT and saline infusion milk yield decreased 11.1%. Milk yield and physiological responses suggested intramammary 5-HT and METH doses were high enough to cause systemic effects. Infusing saline, METH, and 5-HT increased milk SCC. Infusing 5-HT tended to reduce mean lactose concentration (4.3 vs. 4.6%) relative to saline. Milk protein content was decreased by METH and SAL (2.0%) and was increased (5.8%) by 5-HT followed by a 33% decrease postinfusion. Infusion of METH increased evaporative heat loss 11%, which decreased 11% postinfusion. Infusions of 5-HT or METH did not affect plasma nonesterified fatty acid or glucose concentrations, respiration rate, or milk fat content. We conclude 5-HT infusion reduced milk synthesis, whereas blocking the 5-HT receptor with METH increased milk synthesis. Doses of 5-HT and METH used in this study likely resulted in systemic effects. These data support the concept that 5-HT is a feedback inhibitor of lactation in the bovine.

Cost analysis of erythropoietin versus blood transfusions for cervical cancer patients receiving chemoradiotherapy.

PURPOSE: Red blood cell (RBC) transfusions or erythropoietin (EPO) can be used to evade the detrimental effects of anemia during radiotherapy, but the economic consequences of selecting either intervention are not well defined. The RBC transfusion needs during chemoradiotherapy for cervix cancer were quantified to allow comparison of RBC transfusion costs with the projected cost of EPO in this setting. METHODS AND MATERIALS: For patients receiving pelvic radiotherapy, weekly cisplatin, and brachytherapy, the RBC units transfused during treatment were tallied. RBC transfusion costs per unit included the blood itself, laboratory fees, and expected value (risk multiplied by cost) of transfusion-related viral illness. EPO costs included the drug itself and supplemental RBC transfusions when hemoglobin was not adequately maintained. An EPO dosage based on reported usage in cervix cancer patients was applied. RESULTS: Transfusions were given for hemoglobin <10 g/dL. Among 12 consecutive patients, 10 needed at least 1 U of RBC before or during treatment, most commonly after the fifth week. A total of 37 U was given during treatment, for an average of 3.1 U/patient. The sum total of the projected average transfusion-related costs was $990, compared with the total projected EPO-related costs of $3869. CONCLUSIONS: Because no proven clinical advantage has been documented for EPO compared with RBC transfusions to maintain hemoglobin during cervix cancer treatment, for most patients, transfusions are an appropriate and appealingly less expensive option.

Long-term local control and survival after concomitant boost accelerated radiotherapy for locally advanced cervix cancer.

Between 1989 and 1994, a prospective clinical trial tested the safety and efficacy of concomitant boost accelerated superfractionated (CBASF) radiotherapy for patients with locally advanced cervix cancer. CBASF radiotherapy included 45 Gy/25 fractions to the pelvis and a 14.4 Gy/9 fraction concomitant boost to the primary tumor, followed by brachytherapy for a total point A dose of 85 Gy to 90 Gy. The 22 patients of International Federation of Gynecology and Obstetrics stages IIIA-IVA who received CBASF radiotherapy now have a median follow-up time of more than 8 years. The 7-year actuarial rates of local control and overall survival are 81% and 36%, respectively. Serious late toxicity included bowel injury requiring colostomy in eight patients within 2.5 years after treatment, but no other severe toxicity was observed after longer follow-up intervals. The local control and survival rates achieved with CBASF radiotherapy were higher than those observed within a matched contemporaneous cohort of patients treated with standard radiotherapy alone at the same institution (p = 0.1 for local control, 0.09 for survival). The encouraging trend toward improved tumor control, tempered by the complication rate, suggests an opportunity to apply more sophisticated radiotherapy techniques that might sustain the favorable effects of dose intensification while mitigating the normal tissue toxicity.

Comparability of WAIS--R Digit Symbol and the Symbol Digit Modalities Test.

100 persons referred for neuropsychological evaluation were administered both the Symbol Digit Modalities Test and the WAIS--R Digit Symbol subtest. The two sets of scores correlated 0.85, but standard scores derived from the Symbol Digit Modalities Test were significantly lower than standard scores based on Digit Symbol. The mean score on the former for these subjects is the equivalent of 2 1/2 to 3 WAIS--R age-scaled score points lower than the respective Digit Symbol mean.

Significance of atypical cervical cytology in pregnancy.

To ascertain the significance of squamous atypia encountered during routine Papanicolaou smear screening in pregnancy, we reviewed our experience with 76 pregnant women seen during a 4-year period. All were evaluated with repeat cytology and colposcopy during pregnancy and again postpartum. Colposcopic examination during pregnancy revealed a normal transformation zone without evidence of intraepithelial neoplasia in 46 women. In six of these women, repeat cytology was interpreted as cervical intraepithelial neoplasia (CIN) grade 1. In 30 women, an abnormal transformation zone was identified--14 with a negative repeat cytology. In five women, the transformation zone was interpreted as compatible with CIN 2 or CIN 3. Colposcopically directed biopsies were performed in 31 women, in all but two postpartum. Of the 76 women, human papilloma virus or CIN was identified on biopsy in 16 women (21%). We propose that an isolated report of atypical squamous cells on cervical cytology obtained at the initial prenatal visit does not warrant colposcopic evaluation during pregnancy, unless a repeat cytology suggests CIN. Repeat cytology and evaluation to exclude infections and inflammatory lesions is appropriate. However, if a subsequent cytology is abnormal, postpartum colposcopy and colposcopically directed biopsies seem appropriate, since the prevalence of HPV or CIN was 21%.

Endocervical cell recovery.

Three thousand six hundred fourteen Papanicolaou smear reports were evaluated for endocervical cells and characteristics of the patients at the time the slide was taken. Differences were found related to the age of the patient, pregnancy/postpartum status, and cytology. The use of hormones when the smear was taken did not appear to affect the presence of endocervical cells. Many clinicians, believing that not obtaining endocervical cells results from failure to sample the endocervical canal, repeat those smears. This study is consistent with previous ones in finding that other factors, including patient characteristics, have a definite effect on the results. Repeating smears solely for lack of endocervical cells does not appear to be warranted for either the patient or the provider.

Clinical significance of hyperkeratosis and parakeratosis in otherwise negative Papanicolaou smears.

To ascertain the clinical significance of hyperkeratosis and parakeratosis in otherwise negative Papanicolaou smears, we retrospectively reviewed 96 patients with these findings seen during a 32-month period. Evaluation included repeating the smear and performing colposcopy in all patients. Colposcopically directed biopsy and endocervical curettage were performed when appropriate. Only one patient had human papillomavirus (HPV) infection. The isolated finding of hyperkeratosis or parakeratosis was not associated with an increased incidence of cervical intraepithelial neoplasia or HPV and, clinically, was not associated with uterine descensus or vaginal prolapse.

Bleomycin, vincristine, and mitomycin C (BOM) as second-line treatment after failure of cis-platinum-based combination chemotherapy for recurrent cervical cancer.

Seventeen patients with recurrent cervical cancer were prospectively treated with a combination of bleomycin, vincristine, and mitomycin C (BOM). All patients had previously failed a cis-platinum-containing combination regimen. There were no complete responses. Four patients had partial responses, six patients had stable disease, and seven patients had no response. The median length of survival for responders was the same as that for nonresponders (5 months). More than 50% of patients experienced significant toxicity. The combination of bleomycin, vincristine, and mitomycin C appears to be ineffective as a second-line chemotherapy regimen against recurrent cervical cancer previously treated with cis-platinum.

Value of repeat cytology at the time of colposcopy for the evaluation of cervical intraepithelial neoplasia on Papanicolaou smears.

The significance of repeat cervical cytology was evaluated in patients referred for colposcopy because of previous cervical intraepithelial neoplasia (CIN) 1 on cytologic smears. Between Jan 1, 1984, and Dec 31, 1986, 273 such patients were seen. The results of the repeat smears obtained prior to colposcopy were compared with those of colposcopically directed biopsies and of follow-up. The repeat smear was negative in 99 patients; it disclosed squamous atypia in 84, CIN 1 in 64 and CIN 2 or 3 in 26. Thirty-two patients whose repeat smear was negative had biopsy-documented CIN 1-3. Of the 84 patients with squamous atypia, 37 (44%) had biopsy-documented CIN 1-3. Thus, second smears in this group failed to disclose precancerous lesions in at least 69 patients. Of the 90 patients whose repeat smear were interpreted as showing CIN, 64, or 71%, had biopsy-documented CIN 1-3. Patients with a repeat smear showing CIN 1 or greater and normal colposcopy or a negative cervical biopsy must be followed closely: 33% of our study group (6 of 18) were found to have CIN later.

Squamous atypia on cytology. The influence of age.

The optimal management of squamous atypia on cytology has not been determined. Colposcopy has been recommended because of the high false-negative rate of cytology. To evaluate colposcopy, 1,074 consecutive, nonpregnant women presenting with squamous atypia on cytology were examined prospectively with colposcopy and simultaneous repeat cytology. No specific treatment was given prior to evaluation. Biopsy and endocervical curettage were performed when clinically indicated. Two hundred two women (18.8%) had abnormal cervical or vaginal biopsies, 74 had human papillomavirus, and 128 had cervical intraepithelial neoplasia with or without associated papillomavirus infection. Invasive cancer was not detected. Repeat cytology suggested intraepithelial neoplasia in 60 women, 37 (61%) of whom had positive biopsy findings. Such biopsy findings were obtained in 89 of 306 women (29.1%) with repeat squamous atypia on cytology and in 76 of 708 women (10.8%) with repeat negative cytology. When the data were stratified in terms of age, 184/787 (19.6%) abnormal biopsies occurred in women less than or equal to 40 years of age and 18/287 (6.3%) in women greater than or equal to 41. Squamous atypia on cytology should not be ignored. However, women greater than or equal to 41 are at lower risk of having colposcopically detectable abnormalities and can be followed more conservatively.

Heparin-associated thrombocytopenia: a complication of low-dose heparin prophylaxis.

The authors describe a 61-year-old white female who received low-dose heparin prophylaxis in conjunction with a radical vulvectomy with abdomino-perineal resection for stage III Bartholin gland carcinoma and subsequently developed heparin-associated thrombocytopenia with thrombosis. This phenomenon occurs in 0.1% of patients exposed to heparin therapy and has been reported as having a mortality rate of 29% and a 21% rate of limb loss. It is thought to be caused by a heparin-dependent IgG platelet-aggregating antibody. Because of the widespread use of heparin prophylaxis in surgery, the clinician needs to be aware of this complication.

Significance of a positive Papanicolaou smear in a well screened population.

Of 35,937 gynecologic cytology specimens obtained from the cervix or vagina at our institution during a three-year period, 18 (0.05%) were reported as malignant; ten of these 18 (56%) positive results were due to carcinoma arising from sites other than the cervix or vagina. The site of the primary lesion was the endometrium in four patients, the ovary in three, the colon in one, and the breast in one; in one patient the site of the primary carcinoma was unknown. In our patient population a a positive Papanicolaou smear was more often indicative of a noncervical than a cervical malignancy. In addition to detecting preinvasive and invasive malignancies of the cervix and/or vagina, an annual cytologic smear may hasten the detection of extravaginal primary carcinomas.

The significance of atypical cervical cytology in an older population.

To ascertain the significance of squamous atypia encountered during routine Papanicolaou smear screening in an older population, we reviewed 115 consecutive patients over age 50 seen during a 3-year period. Evaluation included repeating the smear and performing colposcopy in all patients. Colposcopically directed biopsy and endocervical curettage were performed when appropriate. Sixty-seven patients (58.3%) had atrophy, 43 (37.4%) were normal, two (1.7%) had cervical intraepithelial neoplasia grade 1, two (1.7%) had cervical intraepithelial neoplasia grade 2, and one (0.9%) had human papillomavirus (HPV) infection. There was a strong association between squamous atypia and estrogen deficiency. With the correction of the estrogen deficiency, the squamous atypia reverted to normal in a statistically significant percentage of patients. A Papanicolaou smear report of squamous atypia in women over age 50 should not be considered normal; further evaluation is required. The incidence of cervical or vaginal intraepithelial neoplasia and HPV infection is much lower than reported in studies involving younger patients.

Urethral placement through a bilateral myocutaneous gracilis flap neovagina.

Malignant melanoma of the vagina is an uncommon genital tumor. When the lesion arises in the distal vagina, radical surgery has been the only treatment to produce long-term survivors. A total vaginectomy, vulvectomy, and bilateral groin node dissection is recommended to assure adequate margins. Sexual function is lost unless reconstruction is performed. The bilateral myocutaneous gracilis flap neovagina has been a successful plastic procedure after exenterative procedures that result in loss of bladder and/or rectum. The authors present a technique in which bladder function was preserved after creation of a gracilis flap neovagina in a patient with Stage I melanoma of the distal vagina. Placement of the distal urethra through the reconstructed gracilis flap neovagina resulted in preservation of urinary function and continence, primary closure of the vulvar defect, and satisfactory sexual function. Two and one-half years after surgery the patient has good bladder and vaginal function without significant sequel.

Pentobarbital's effect in a combination antiemetic regimen for cisplatin induced nausea and vomiting.

Twelve patients with histologically confirmed gynecologic cancer treated with a chemotherapy regimen containing cisplatin were randomized in a double-blind cross-over trial utilizing two antiemetic combination regimens during the first four treatment courses. Regimen A consisted of pentobarbital, prochlorperazine, and dexamethasone. Regimen B contained dexamethasone, prochlorperazine, and placebo. Patients chose Regimen A over B 70% of the time (p less than 0.0268). In 50% of the treatment courses, objective assessment of Regimen A's antiemetic effect was complete compared with 4.5% for Regimen B. Sleep and reduced apprehension of cisplatin-induced emesis were the major factors why patients chose Regimen A. The authors concludes that intravenous pentobarbital-induced sleep, when added to a combination antiemetic regimen, is effective in reducing vomiting episodes. Moreover, it provides a more pleasant chemotherapy experience in patients undergoing cisplatin containing chemotherapy.