A high salt diet inhibits obesity and delays puberty in the female rat.

BACKGROUND/OBJECTIVES: Processed foods are considered major contributors to the worldwide obesity epidemic. In addition to high sugar and fat contents, processed foods contain large amounts of salt. Owing to the correlations with rising adiposity, salt has recently been proposed to be obesogenic. This study investigated three hypotheses: (i) high salt contributes to weight gain and adiposity in juvenile female rats, (ii) puberty onset would be altered because salt is known to affect neuronal systems involved in activating the reproductive system, and (iii) enhanced adiposity will act synergistically with salt to drive early puberty onset. DESIGN: Female weanling rats (post-natal day 21, n=105) were fed a low fat/low salt diet, low fat/high salt diet, high fat/low salt diet or a high salt/high fat diet for 24 days. Metabolic measures, including weight gain, food intake, fecal output, activity and temperature were recorded in subsets of animals. RESULTS: Body weight, retroperitoneal and perirenal fat pad weight, and adipocyte size were all lower in animals fed high fat/high salt compared with animals fed high fat alone. Leptin levels were reduced in high fat/high salt fed animals compared with high fat/low salt-fed animals. Daily calorie intake was higher initially but declined with adjusted food intake and was not different among groups after 5 days. Osmolality and corticosterone were not different among groups. Fecal analysis showed excess fat excretion and a decreased digestive efficiency in animals fed high fat/low salt but not in animals fed high fat/high salt. Although respiratory exchange ratio was reduced by high dietary fat or salt, aerobic-resting metabolic rate was not affected by the diet. High salt delayed puberty onset, regardless of dietary fat content. CONCLUSIONS: Salt delays puberty and prevents the obesogenic effect of a high fat diet. The reduced weight gain evident in high salt-fed animals is not due to differences in food intake or digestive efficiency.

Avian influenza surveillance in Central and West Africa, 2010-2014.

Avian influenza virus (AIV) is an important zoonotic pathogen, resulting in global human morbidity and mortality and substantial economic losses to the poultry industry. Poultry and wild birds have transmitted AIV to humans, most frequently subtypes H5 and H7, but also different strains and subtypes of H6, H9, and H10. Determining which birds are AIV reservoirs can help identify human populations that have a high risk of infection with these viruses due to occupational or recreational exposure to the reservoir species. To assess the prevalence of AIV in tropical birds, from 2010 to 2014, we sampled 40 099 birds at 32 sites in Central Africa (Cameroon, Central African Republic, Congo-Brazzaville, Gabon) and West Africa (Benin, Côte d'Ivoire, Togo). In Central Africa, detection rates by real-time RT-PCR were 16·6% in songbirds (eight passerine families, n = 1257), 16·4% in kingfishers (family Alcedinidae, n = 73), 8·2% in ducks (family Anatidae, n = 564), and 3·65% in chickens (family Phasianidae, n = 1042). Public health authorities should educate human cohorts that have high exposure to these bird populations about AIV and assess their adherence to biosecurity practices, including Cameroonian farmers who raise small backyard flocks.

Staging lymphadenectomy in patients with localized high risk prostate cancer: comparison of the laparoendoscopic single site (LESS) technique with conventional multiport laparoscopy.

BACKGROUND: In patients with localized high-risk prostate cancer awaiting radiation therapy, pelvic lymphadenectomy (PL) is a reliable minimally invasive staging procedure. We compared outcomes after laparoendoscopic single site PL (LESSPL) with those after conventional multiport laparoscopic PL (MLPL). METHODS: A retrospective case-control study was carried out at the authors' center. For LESSPL the reusable X-Cone single port was combined with straight and prebent laparoscopic instruments and an additional 3 mm needlescopic grasper. MLPL was performed via four trocars of different sizes using standard laparoscopic instruments. RESULTS: Patients who underwent either LESSPL (n = 20) or MLPL (n = 97) between January 2008 and July 2013, were included in the study. Demographic data were comparable between groups. Patients in the LESSPL group tended to be older and had a significantly higher ASA-score. The mean operating time was 172.4 ± 34.1 min for LESSPL and 116.6 ± 40.1 min for MLPL (P < .001). During LESSPL, no conversion to MLPL was necessary. An average of 12 lymph nodes per patient was retrieved, with no significant difference between study groups. Postoperative pain scores were similar between groups. The hospital stay was 2.3 ± 0.7 days after LESSPL and 3.1 ± 1.2 days after MLPL (P = .01). Two days postoperatively, significantly more patients after LESSPL than after MLPL recovered their normal physical activity (P < .001). Six months postoperatively, no complications were registered in the LESSPL group and cosmetic results were excellent. CONCLUSIONS: In the present study, shorter hospitalization and quicker postoperative recovery were major benefits of LESSPL over MLPL. In patients with localized prostate cancer, staging LESS pelvic lymphadenectomy may be a safe alternative to conventional multiport laparoscopy.

Outcomes after laparoscopic living donor nephrectomy: comparison of two laparoscopic surgeons with different levels of expertise.

OBJECTIVE: To test the effect of surgeon experience on donor and recipient outcomes after laparoscopic living donor nephrectomy (LLDN). Results of a LLDN expert were compared with those of an LLDN novice. PATIENTS AND METHODS: Between October 2008 and October 2010 the last 20 cases of a series of 130 consecutive LLDNs, performed by an expert (EXP) were compared with the first 20 cases of an LLDN novice (NOV). Donor and recipient outcomes were evaluated. The novice was mentored by the expert during his initial four LLDN cases. RESULTS: Donor and recipient demographics were not different between the two surgeon groups. Total operating time and warm ischaemia time during LLDN was significantly longer in the NOV group compared with the EXP group (273 min vs 147 min and 213 s vs 162 s, respectively). The incidence of donor complications was low in both groups. Length of hospital stay among donors did not differ between groups. Although delayed graft function, rejection rates and postoperative serum creatinine levels indicated slightly poorer recipient outcomes in the NOV group, differences did not reach statistical significance. CONCLUSIONS: Mentoring by an experienced urological laparoscopist may help an LLDN novice to generate acceptable donor and recipient outcomes. Whether or not prolonged operating times and warm ischaemia times during the early phase of an LLDN experience are risk factors for impaired graft function needs further evaluation.

Outcome of expanded criteria donor kidneys that were transplanted at other Eurotransplant centers after being rejected by our institution.

PURPOSE: There is a growing discrepancy between the demand for renal transplants and the number of transplants conducted. For the many patients on the renal transplant waiting list, this means increased dialysis-associated morbidity, mortality and a reduced quality of life. The aim of this study was to ascertain whether it is justifiable for transplant centers to reject cadaveric donor organs on hand of marginal organ quality. METHODS: We identified 110 kidneys that were primarily rejected for transplantation at Charité Universitätsmedizin Berlin, Campus Mitte, and later transplanted at another center within the Eurotransplant zone. Using data from the Collaborative Transplant Study, we analyzed various demographic donor data including cold ischemia times, as well as graft and recipient outcomes. RESULTS: The median follow-up was 54 months. The cold ischemia time averaged 16 h. The organs that were primarily rejected by our center and then transplanted at other Eurotransplant centers showed 31 % of recipients had creatinine levels under 1.47 mg/dl and 94 % had levels under 2.97 mg/dl at 3-year follow-up. The mean death-censored graft survival was 71.4 months. The mean renal transplant recipient survival was 87.5 months. CONCLUSIONS: Based on our findings, we propose that acceptance criteria for marginal donor kidneys need to be widened.

Pre-operative assessment of living renal transplant donors with state-of-the-art imaging modalities: computed tomography angiography versus magnetic resonance angiography in 118 patients.

PURPOSE: To compare current technology multislice computed tomography angiography (CTA) with magnetic resonance angiography (MRA) in the pre-operative evaluation of vascular anatomy of living renal transplant donors. METHODS AND MATERIALS: Two hundred and thirty-six kidneys were included in the CTA and MRA analysis. Renal vasculature was evaluated independently by two readers in each modality with a delay of 4 weeks between reading sessions. Surgical correlation on the operated side was available in all patients. The reference standard was defined by surgical correlation and consensus reading of both modalities. RESULTS: Detection rate of CTA for arteries was 99.1 and 95.0 % for reader 1 and reader 2, respectively. Detection rate of MRA for arteries was 95.0/94.3 %. Most of the undetected arteries were ≤ 1 mm diameter (reader 1: 2 of 3 in CTA and 9 of 16 in MRA; reader 2: 11 of 16 in CTA, and 8 of 18 in MRA). Detection rates for arteries ≥ 2 mm for reader 1/reader 2 were 99.7/98.7 % in CTA and 99.1/97.8 % in MRA, respectively. Detection rates for veins were 99.6/97.4 % in CTA and 97.8/96.9 % in MRA, respectively. Both readers misdiagnosed between 0 and 1 non-present arteries and between 2 and 3 non-present veins in both modalities. CONCLUSIONS: Modern multislice CT and MRI scanners allow highly accurate evaluation of the vascular anatomy, especially for vessels of ≥ 2 mm diameter. CTA may provide slightly better depiction of very small arteries; however, this may be reader-dependent. Additional factors affecting the choice of imaging modality should include local availability, cost, and the desire to avoid ionizing radiation in healthy transplant donors.

Volume matters: CT-based renal cortex volume measurement in the evaluation of living kidney donors.

Currently, no international standard for the pre-transplant evaluation of living donor renal function exists. Following a standardized questionnaire on current practice in all Eurotransplant (ET) centers, we compared a new CT-based technique to measure renal cortex volume with our standard of DTPA-clearance combined with MAG3-scintigraphy (DTPA × MAG3) and with creatinine-based methods in 167 consecutive living kidney donors. Most ET centers use creatinine-clearance (64%) to measure total renal function and radioistopic methods (82%) to assess split renal function. Before transplantation, CT-measured total cortex volume (r = 0.67; P < 0.001) and estimated GFR using the Cockcroft-Gault formula [eGFR(CG)] (r = 0.55; P < 0.001) showed the strongest correlation with DTPA-clearance. In contrast, the correlation between DTPA-clearance and creatinine clearance was weak (r = 0.21; P = 0.02). A strong correlation was observed between CT-measured split cortex volume and MAG3-measured split renal function (r = 0.93; P < 0.001). A strong correlation was also found between pre-transplant split renal function assessed by eGFR(CG) together with cortex volume measurement and post-transplant eGFR(CG) of both, the donor (r = 0.83; P < 0.001) and the recipient (r = 0.75; P < 0.001). In conclusion CT-based assessment of renal cortex volume bears the potential to substitute existing methods to assess pre-transplant living donor split renal function.

Impact of surgeon experience on complication rates and functional outcomes of 484 deceased donor renal transplants: a single-centre retrospective study.

OBJECTIVE: To determine how postoperative and functional outcomes after deceased donor renal transplantation (DDRT) are related to surgeon experience. PATIENTS AND METHODS: The outcomes of 484 adult DDRT performed by 13 urological surgeons were retrospectively reviewed. After completion of a staged renal transplant training programme under supervision of an attending urological transplant surgeon, the 13 surgeons were either assigned to the inexperienced group (n = 8) or the experienced group (n = 5). Surgeons in the experienced group had performed more than 30 unsupervised DDRT in a standard fashion with routine ureteric stenting. Between 1988 and 2005, inexperienced surgeons performed 152 DDRT, whereas experienced surgeons performed 332 DDRT. RESULTS: Patient and graft survival at 2 hyears were 98% and 94.7%, respectively. Early graft loss in five recipients was unrelated to surgeon experience. Delayed graft function occurred in 29% of cases and median 1-year serum-creatinine was 1.48 mg/dL, with no difference between surgeon groups. Postoperative bleeding and lymphocele formation were the most frequent surgical complications, with an equal distribution between groups. Ureteric complications had a significantly higher incidence among inexperienced surgeons (6.6% versus 2.7%; P = 0.04). CONCLUSION: We conclude that DDRT as performed by inexperienced urological renal transplant surgeons has both acceptable short- and long-term outcomes.

Long-term outcomes of living donor kidney transplants in pediatric recipients following laparoscopic vs. open donor nephrectomy.

We compared long-term outcomes of LDKT in pediatric recipients following either laparoscopic (LDN) or ODN. In our retrospective single-center study, we compared 38 pediatric LDKT recipients of a laparoscopically procured kidney with a historic ODN group comprising 17 pediatric recipients. In our center, the first pure laparoscopic non-hand-assisted LDN for a pediatric LDKT recipient was performed in June 2001. Demographic data of donors and recipients were comparable between groups. Mean follow-up was 64 months in the LDN group and 137 months in the ODN group. Patient survival was comparable between groups. Graft survival at one and five yr was 97% (LDN) vs. 94% (ODN) and 91% (LDN) vs. 88% (ODN; p = n.s.), respectively. Serum creatinine at one and five yr was 1.16 ± 0.47 mg/dL (LDN) vs. 1.02 ± 0.38 mg/dL (ODN) and 1.38 ± 0.5 mg/dL (LDN) vs. 1.20 ± 0.41 mg/dL (ODN), respectively. The type and frequency of surgical complications did not differ between groups. DGF and acute rejection rates were similar between groups. In the ODN group, a higher proportion of right donor kidneys was used. In the ODN group, all kidneys had singular arteries, whereas in the LDN group five kidneys had multiple arteries. Arterial multiplicity was associated with a higher incidence of DGF. In our experience, LDN does not compromise long-term graft outcomes in pediatric LDKT recipients. Arterial multiplicity of the donor kidney may be a risk factor for impaired early graft function in the pediatric population.

Inhibition of 20-HETE synthesis and action protects the kidney from ischemia/reperfusion injury.

20-Hydroxyeicosatetraenoic acid (20-HETE) production is increased in ischemic kidney tissue and may contribute to ischemia/reperfusion (I/R) injury by mediating vasoconstriction and inflammation. To test this hypothesis, uninephrectomized male Lewis rats were exposed to warm ischemia following pretreatment with either an inhibitor of 20-HETE synthesis (HET0016), an antagonist (20-hydroxyeicosa-6(Z),15(Z)-dienoic acid), an agonist (20-hydroxyeicosa-5(Z),14(Z)-dienoic acid), or vehicle via the renal artery and the kidneys were examined 2 days after reperfusion. Pretreatment with either the inhibitor or the antagonist attenuated I/R-induced renal dysfunction as shown by improved creatinine clearance and decreased plasma urea levels, compared to controls. The inhibitor and antagonist also markedly reduced tubular lesion scores, inflammatory cell infiltration, and tubular epithelial cell apoptosis. Administering the antagonist accelerated the recovery of medullary perfusion, as well as renal medullary and cortical re-oxygenation, during the early reperfusion phase. In contrast, the agonist did not improve renal injury and reversed the beneficial effect of the inhibitor. Thus, 20-HETE generation and its action mediated kidney injury due to I/R. Whether or not these effects are clinically important will need to be tested in appropriate human studies.

No need for systemic heparinization during laparoscopic donor nephrectomy with short warm ischemia time.

PURPOSE: Systemic heparin administration during laparoscopic donor nephrectomy (LDN) may prevent microvascular thrombus formation following warm ischemia. We herein present our experience with and without systemic heparinization during LDN. METHODS: We retrospectively reviewed donor complications and graft outcomes in 119 consecutive live donor kidney transplantations between January 2005 and December 2009. Systemic heparin was administered to the first 65 donors. LDN was carried out by 2 surgeons using a pure laparoscopic technique. RESULTS: Total operating time for LDN was significantly longer in the heparin group (202 vs. 157 min). The incidence of renal artery multiplicity was significantly higher in the heparin group. Mean warm ischemia time was 160 s, and mean hospital stay was 5 days with no differences between groups. Postoperative hemorrhage occurred in 3 donors with systemic heparinization and in 1 without heparinization. Two donors received blood transfusions, and 2 underwent laparoscopic reexploration. Three grafts were lost in the heparin group and 1 in the non-heparin group. Graft loss was due to early vascular thrombosis (n = 3) and due to acute rejection (n = 1). Overall, 1-year graft survival was 96.6%, and 1-year serum creatinine was 1.41 mg/dl (P = n. s. between groups). CONCLUSIONS: Abandoning systemic donor heparinization in LDN with short warm ischemia has a low complication rate without adverse effects on short- and long-term graft outcomes.

Demonstration of a third structurally distinct human Ia beta chain by two-dimensional gel electrophoresis.

Previous studies have indicated that HLA-DR homozygous cell lines express two Ia alpha and Ia beta chains that combine to form at least two Ia molecules. This report demonstrates by two-dimensional gel electrophoresis the existence of a third structurally distinct human Ia beta chain on DR2 and DR5 cell lines. This suggests that at least five separate genes control the expression of Ia molecules on HLA-DR homozygous cell lines.

The 'blood group O problem' in kidney transplantation--time to change?

BACKGROUND: Patients with blood group O have disadvantages in the allocation of deceased donor organs in the Eurotransplant Kidney Allocation System and fewer ABO-compatible living donors. In order to investigate the consequences of this dilemma, we analysed the outcome of patients with blood group O in our transplantation programme. METHODS: A single-centre analysis of 1186 waitlisted patients for first deceased donor kidney transplantations between 1996 and 2008 was performed, and the mechanisms of blood group-dependent differences for graft and recipient outcome were assessed. RESULTS: Median follow-up time until death or end of observation for all waitlisted patients was 66 months (range, 0-158 months) and for 589 recipients of a kidney graft was 61 months (range, 0-158 months). Patients with blood group O had significantly longer waiting times for deceased donor kidney grafts, compared to non-group O recipients (median waiting time, 85 vs 59 months). As a consequence, blood group O patients had an increased risk for death without transplantation (13.1% for O patients vs 9.6% for non-O patients; P < 0.05). Despite a good human leukocyte antigen match, graft outcome tended to be worse in O recipients; 14.1% (95% CI, 8.2-19.9%) of all O kidneys from deceased donors were transplanted into non-O recipients, leading to the accumulation of O recipients on the waiting list. CONCLUSIONS: The export of blood group O donor kidneys to other blood groups leads to longer waiting times, to a higher death rate and to accumulation of blood group O patients on the waiting list, which will further aggravate the problem in the future. Our results should prompt further research on the issues associated with blood group O. Current allocation systems and living donor kidney exchange programmes should be re-evaluated to address this problem.

Outcomes of transplanting deceased-donor kidneys between elderly donors and recipients.

Rate of acceptance of deceased-donor kidneys decreases with donor age despite the growing number of aged transplant candidates on the waiting list. In the Eurotransplant Senior Program, HLA-unmatched kidneys from deceased donors aged > or = 65 yr are transplanted regionally into recipients aged > or = 65 yr. Because we have become more willing to accept kidneys from donors aged > or = 75 yr than previous years, we performed a retrospective analysis of this subgroup. Kidneys were accepted from donors aged > or = 75 yr provided a normal creatinine on admission to the hospital, a Cockcroft-Gault creatinine clearance > 80 ml/min, and an absence of comorbidities. We compared outcomes of kidneys from donors aged > or = 75 yr with both younger-donor kidneys transplanted in the Eurotransplant Senior Program and with younger-donor HLA-matched kidneys transplanted into recipients > or = 60 yr. There were no differences in 5-yr graft and patient survival or rate of delayed graft function between groups. Graft function, measured by creatinine and creatinine clearance, differed without pattern at only three of 12 time points during 5 yr of follow-up. In conclusion, our data suggest that kidneys from deceased donors aged > or = 75 yr can be transplanted safely into recipients aged > or = 65 yr if similar donor criteria and local allocation practices are used.

[A retrospective analysis of functional and oncologic outcomes following surgical treatment of patients with pT1/pT2 renal cell carcinoma at a tertiary referral centre]. / Peri- und postoperatives Ergebnis nach Nierentumorchirurgie bei pT1/pT2 Nierenzellkarzinom ­ eine retrospektive Zentrumsanalyse der funktionellen und onkologischen Ergebnisse.

INTRODUCTION: In patients with localised renal cell carcinoma, the only curative treatment option is surgical tumour excision. The aim of this study was to evaluate peri- and postoperative outcomes as well as oncologic and functional long-term results following surgical treatment of patients with renal cell carcinoma (pT1/pT2) at a tertiary referral centre. PATIENTS AND METHODS: This retrospective study included a total of 758 patients with localised renal cell carcinoma (pT1 /pT2), who underwent radical (RN) or partial (PN) nephrectomy between 01/2008 and 10/2014. Pre-, peri- and postoperative parameters were recorded. Oncologic and functional long-term data were retrieved through questionnaires and structured telephone interviews. RESULTS: Laparoscopic RN or PN resulted in less blood loss and lower peri- and postoperative complication rates compared to open procedures. Regarding short- and long-term renal function, a higher increase in serum creatinine levels was detected after RN. No difference was noted in health status and quality of life. Median follow-up was 36 months. A total of 10.4 % of patients died during follow-up. 4.7 % and 8.4 % developed a relapse or metastatic disease. No difference was found between laparoscopic and open RN/PNs in terms of oncologic long-term results. DISCUSSION: In conclusion, all surgical techniques evaluated in this study provided good oncologic and functional short-/long-term outcomes.

HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals.

Characterization of the host immune response to human immunodeficiency virus type 1 (HIV-1) is critical to the rational design of an effective AIDS vaccine. In this study, cytotoxic T lymphocytes (CTL) specific for HIV-1 reverse transcriptase (RNA-dependent DNA polymerase) were found in blood samples from HIV-1-infected individuals. CTL targets were prepared by immortalizing B cells from ten seropositive and six seronegative individuals, and then infecting these cells with recombinant vaccinia viruses containing HIV-1 genes. CTL directed against autologous B lymphoblasts expressing HIV-1 reverse transcriptase were detected in fresh blood samples from eight HIV-1 seropositive subjects, but in no seronegative controls. The effector cells were identified as major histocompatibility complex-restricted CD3+CD8+ lymphocytes. Because the HIV-1 pol gene is highly conserved among different isolates and generates both humoral and cellular immune responses, it bears consideration for inclusion in a candidate AIDS vaccine.

Immunity to antigens associated with primate C-type oncoviruses in pregnant women.

Cell-mediated and humoral immune responses against antigens associated with primate C-type oncoviruses were evaluated in humans by microcytotoxicity and radioimmunoprecipitation assays. Five of six women tested sequentially during pregnancy developed selective cell-mediated reactivity against baboon endogenous virus (BEV)--infected human fibroblasts. Responsiveness peaked during the second and third trimesters and corresponded temporally with elevated antibody levels to BEV antigens. Similar cell-mediated reactivity was not observed in nonpregnant individuals. Selective cell-mediated reactivity directed against cells infected with the simian sarcoma virus-simian sarcoma associated virus complex (SSV--SSAV) was observed in four of 20 healthy adults (three of 14 nonpregnant, one of six pregnant). These observations suggest that cell-mediated reactivity against primate C-type oncoviruses is occasionally detected in healthy nonpregnant adults, but that during pregnancy both cell-mediated and humoral reactivity against BEV may become selectively expressed.

Reversible depression in myocardial performance in dogs with experimental phosphorus deficiency.

The effects of phosphorus depletion on cardiac muscle function in six awake dogs were evaluated with surgically implanted transducers to serially measure ascending aortic root blood flow and high fidelity left ventricular pressure. After the animals recovered from surgery, phosphorus depletion was induced by feeding them a synthetic phosphorus-deficient diet plus aluminum carbonate gel for 35 days, followed by the same diet with phosphorus supplementation for 21 days. In addition to the cardiac studies, sequential measurements of phosphorus content in skeletal muscle and phosphorus in serum were obtained to ascertain the level of phosphorus depletion. Serum inorganic phosphorus concentration (mg/100 ml) decreased from 5.1 +/- 0.1 on day 0 to 0.9 +/- 0.1 on day 35 (P less than 0.01), and total muscle phosphorus (content mmul/100 g fat-free dry weight) decreased from 28.0 +/- on day 0 to 22.6 +/- 0.5 on day 35 (P less than 0.01). During the period of phosphorus depletion, there was no significant change in heart rate; however, stroke volume (milliliter) and peak blood flow velocity (centimeter per second) declined from 24 +/- 2 to 17 +/- 2 (P less than 0.01) and 121 +/- 12 to 98 +/- 7 (P less than 0.01), respectively. Maximum ascending aortic blood flow acceleration (centimeter per second square) and maximum left ventricular time rate of change of pressure (mm Hg per second) also decreased from 4,630 +/- 313 to 3,817 +/0 346 (P less than 0.01) and 2,582 +/- 347 to 2,120 +/- 297 (P less than 0.01) during phosphorus depletion. After repletion all values returned to control values. These results indicate that moderate diet-induced phosphorus depletion can depress myocardial performance. With repletion of phosphorus, myocardial performance improves.

Reversible changes of the muscle cell in experimental phosphorus deficiency.

Both animal and human studies suggest that either phosphorus depletion or hypophosphatemia might have an adverse effect on muscle function and composition. Recently a possible deleterious effect was noted in patients with chronic alcoholism. In this unexplained disease, a variety of toxic and nutritional disturbances could affect the muscle cell, thus obscuring the precise role of phosphorus. Accordingly, we examined eight conditioned dogs for the possibility that phosphorus deficiency per se might induce an abnormally low resting transmembrane electrical potential difference (Em) and alter the composition of the muscle cell. Eight conditioned dogs were fed a synthetic phosphorus-deficient but otherwise nutritionally adequate diet plus aluminum carbonate gel for a 28-day period followed by the same diet with phosphorus supplementation for an additional 28 days. Sequential measurements of Em and muscle composition were made at 0 and 28 days during depletion and again after phosphorus repletion. Serum inorganic phosphorus concentration (mg/100 ml) fell from 4.2 +/- 0.6 on day 0 t0 1.7 +/- 0.1 on day 28. Total muscle phosphorus content (mmol/100 g fat-free dry wt [FFDW]) fell from 28.5 +/- 1.8 on day 0 to 22.4 +/- 2.1 on day 28. During phosphorus depletion, average Em (-mV) fell from 92.6 +/- 4.2 to 77.9 +/- 4.1 mV (P less than 0.001). Muscle Na+ and Cl- content (meq/100 g FFDW) rose respectively from 11.8 +/- 3.2 to 17.2 +/- 2.8 (P less than 0.01) and from 8.4 +/- 1.4 to 12.7 +/- 2.0 (P less than 0.001). Total muscle water content rose from 331 +/- 12 to 353 +/- 20 g/100 FFDW (P less than 0.05). A slight, but nevertheless, significant drop in muscle potassium content, 43.7 +/- 2.0-39.7 +/- 2.2 meq/100 g FFDW (P less than 0.05) was also noted. After 4 wk of phosphorus repletion, all of these measurements returned toward control values. We conclude that moderate phosphorus depletion can induce reversible changes in skeletal muscle composition and transmembrane potential in the dog, and it apparently occurs independently of profound hypophosphatemia.

Hypophosphatemia and rhabdomyolysis.

Clinical observations suggest that overt rhabdomyolysis may occur if severe hypophosphatemia is superimposed upon a pre-existing subclinical myopathy. To examine this possibility, a subclinical muscle cell injury was induced in 23 dogs by feeding them a phosphorus- and calorie-deficient diet until they lost 30% of their original weight. To induce acute, severe hypophosphatemia in the animals after partial starvation, 17 of the dogs were given large quantities of the same phosphorus-deficient diet in conjunction with an oral carbohydrate supplement, which together provided 140 kcal/kg per day. After phosphorus and caloric deprivation, serum phosphorus and creatine phosphokinase (CPK) activity were normal. Total muscle phosphorus content fell from 28.0+/-1.3 to 26.1+/-2.5 mmol/dg fat-free dry solids. Sodium, chloride, and water contents rose. These changes resembled those observed in patients with subclinical alcoholic myopathy. When studied after 3 days of hyperalimentation, the animals not receiving phosphorus showed weakness, tremulousness, and in some cases, seizures. Serum phosphorus fell, the average lowest value was 0.8 mg/dl (P <0.001). CPK activity rose from 66+/-357 to 695+/-1,288 IU/liter (P <0.001). Muscle phosphorus content fell further to 21.1+/-7.7 mmol/dg fat-free dry solids (P <0.001). Muscle Na and Cl contents became higher (P <0.01). Sections of gracilis muscle showed frank rhabdomyolysis.6 of the 23 phosphorus- and calorie-deprived dogs were also given 140 kal/kg per day but in addition, each received 147 mmol of elemental phosphorus. These dogs consumed their diet avidly and displayed no symptoms. They did not become hypophosphatemic, their CPK remained normal, and derangements of cellular Na, Cl, and H(2)O were rapidly corrected. The gracilis muscle appeared normal histologically in these animals. These data suggest that a subclinical myopathy may set the stage for rhabdomyolysis if acute, severe hypophosphatemia is superimposed. Neither acute hypophosphatemia nor rhabdomyolysis occur if abundant phosphorus is provided during hyperalimentation.